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Sample records for genomics analyses including

  1. Comparative chloroplast genomics: analyses including new sequences from the angiosperms Nuphar advena and Ranunculus macranthus

    Directory of Open Access Journals (Sweden)

    Boore Jeffrey L

    2007-06-01

    Full Text Available Abstract Background The number of completely sequenced plastid genomes available is growing rapidly. This array of sequences presents new opportunities to perform comparative analyses. In comparative studies, it is often useful to compare across wide phylogenetic spans and, within angiosperms, to include representatives from basally diverging lineages such as the genomes reported here: Nuphar advena (from a basal-most lineage and Ranunculus macranthus (a basal eudicot. We report these two new plastid genome sequences and make comparisons (within angiosperms, seed plants, or all photosynthetic lineages to evaluate features such as the status of ycf15 and ycf68 as protein coding genes, the distribution of simple sequence repeats (SSRs and longer dispersed repeats (SDR, and patterns of nucleotide composition. Results The Nuphar [GenBank:NC_008788] and Ranunculus [GenBank:NC_008796] plastid genomes share characteristics of gene content and organization with many other chloroplast genomes. Like other plastid genomes, these genomes are A+T-rich, except for rRNA and tRNA genes. Detailed comparisons of Nuphar with Nymphaea, another Nymphaeaceae, show that more than two-thirds of these genomes exhibit at least 95% sequence identity and that most SSRs are shared. In broader comparisons, SSRs vary among genomes in terms of abundance and length and most contain repeat motifs based on A and T nucleotides. Conclusion SSR and SDR abundance varies by genome and, for SSRs, is proportional to genome size. Long SDRs are rare in the genomes assessed. SSRs occur less frequently than predicted and, although the majority of the repeat motifs do include A and T nucleotides, the A+T bias in SSRs is less than that predicted from the underlying genomic nucleotide composition. In codon usage third positions show an A+T bias, however variation in codon usage does not correlate with differences in A+T-richness. Thus, although plastome nucleotide composition shows "A

  2. Comparative chloroplast genomics: Analyses including new sequencesfrom the angiosperms Nuphar advena and Ranunculus macranthus

    Energy Technology Data Exchange (ETDEWEB)

    Raubeso, Linda A.; Peery, Rhiannon; Chumley, Timothy W.; Dziubek,Chris; Fourcade, H. Matthew; Boore, Jeffrey L.; Jansen, Robert K.

    2007-03-01

    The number of completely sequenced plastid genomes available is growing rapidly. This new array of sequences presents new opportunities to perform comparative analyses. In comparative studies, it is most useful to compare across wide phylogenetic spans and, within angiosperms, to include representatives from basally diverging lineages such as the new genomes reported here: Nuphar advena (from a basal-most lineage) and Ranunculus macranthus (from the basal group of eudicots). We report these two new plastid genome sequences and make comparisons (within angiosperms, seed plants, or all photosynthetic lineages) to evaluate features such as the status of ycf15 and ycf68 as protein coding genes, the distribution of simple sequence repeats (SSRs) and longer dispersed repeats (SDR), and patterns of nucleotide composition.

  3. Whole-genome resequencing analyses of five pig breeds, including Korean wild and native, and three European origin breeds.

    Science.gov (United States)

    Choi, Jung-Woo; Chung, Won-Hyong; Lee, Kyung-Tai; Cho, Eun-Seok; Lee, Si-Woo; Choi, Bong-Hwan; Lee, Sang-Heon; Lim, Wonjun; Lim, Dajeong; Lee, Yun-Gyeong; Hong, Joon-Ki; Kim, Doo-Wan; Jeon, Hyeon-Jeong; Kim, Jiwoong; Kim, Namshin; Kim, Tae-Hun

    2015-08-01

    Pigs have been one of the most important sources of meat for humans, and their productivity has been substantially improved by recent strong selection. Here, we present whole-genome resequencing analyses of 55 pigs of five breeds representing Korean native pigs, wild boar and three European origin breeds. 1,673.1 Gb of sequence reads were mapped to the Swine reference assembly, covering ∼99.2% of the reference genome, at an average of ∼11.7-fold coverage. We detected 20,123,573 single-nucleotide polymorphisms (SNPs), of which 25.5% were novel. We extracted 35,458 of non-synonymous SNPs in 9,904 genes, which may contribute to traits of interest. The whole SNP sets were further used to access the population structures of the breeds, using multiple methodologies, including phylogenetic, similarity matrix, and population structure analysis. They showed clear population clusters with respect to each breed. Furthermore, we scanned the whole genomes to identify signatures of selection throughout the genome. The result revealed several promising loci that might underlie economically important traits in pigs, such as the CLDN1 and TWIST1 genes. These discoveries provide useful genomic information for further study of the discrete genetic mechanisms associated with economically important traits in pigs.

  4. Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals

    Science.gov (United States)

    Heid, Iris M.; Henneman, Peter; Hicks, Andrew; Coassin, Stefan; Winkler, Thomas; Aulchenko, Yurii S.; Fuchsberger, Christian; Song, Kijoung; Hivert, Marie-France; Waterworth, Dawn M.; Timpson, Nicholas J.; Richards, J. Brent; Perry, John R.B.; Tanaka, Toshiko; Amin, Najaf; Kollerits, Barbara; Pichler, Irene; Oostra, Ben A.; Thorand, Barbara; Frants, Rune R.; Illig, Thomas; Dupuis, Josée; Glaser, Beate; Spector, Tim; Guralnik, Jack; Egan, Josephine M.; Florez, Jose C.; Evans, David M.; Soranzo, Nicole; Bandinelli, Stefania; Carlson, Olga D.; Frayling, Timothy M.; Burling, Keith; Smith, George Davey; Mooser, Vincent; Ferrucci, Luigi; Meigs, James B.; Vollenweider, Peter; van Dijk, Ko Willems; Pramstaller, Peter; Kronenberg, Florian; van Duijn, Cornelia M.

    2009-01-01

    Objective Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0*10-4 for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3*10-24) as well as in both women- and men-specific analyses (p=8.7*10-17 and p=2.5*10-11, respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01). Conclusions We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. PMID:20018283

  5. Comprehensive genomic analyses of the OM43 clade including a novel species from Red Sea indicate ecotype differentiation among marine methylotrophs

    KAUST Repository

    Jimenez Infante, Francy M.

    2015-12-11

    The OM43 clade within the family Methylophilaceae of Betaproteobacteria represents a group of methylotrophs playing important roles in the metabolism of C1 compounds in marine environments and other aquatic environments around the globe. Using dilution-to-extinction cultivation techniques, we successfully isolated a novel species of this clade (designated here as MBRS-H7) from the ultra-oligotrophic open ocean waters of the central Red Sea. Phylogenomic analyses indicate that MBRS-H7 is a novel species, which forms a distinct cluster together with isolate KB13 from Hawaii (H-RS cluster) that is separate from that represented by strain HTCC2181 (from the Oregon coast). Phylogenetic analyses using the robust 16S–23S internal transcribed spacer revealed a potential ecotype separation of the marine OM43 clade members, which was further confirmed by metagenomic fragment recruitment analyses that showed trends of higher abundance in low chlorophyll and/or high temperature provinces for the H-RS cluster, but a preference for colder, highly productive waters for the HTCC2181 cluster. This potential environmentally driven niche differentiation is also reflected in the metabolic gene inventories, which in the case of H-RS include those conferring resistance to high levels of UV irradiation, temperature, and salinity. Interestingly, we also found different energy conservation modules between these OM43 subclades, namely the existence of the NADH:quinone oxidoreductase NUO system in the H-RS and the non-homologous NQR system in HTCC2181, which might have implications on their overall energetic yields.

  6. Comprehensive Genomic Analyses of the OM43 Clade, Including a Novel Species from the Red Sea, Indicate Ecotype Differentiation among Marine Methylotrophs

    Science.gov (United States)

    Jimenez-Infante, Francy; Ngugi, David Kamanda; Vinu, Manikandan; Alam, Intikhab; Kamau, Allan Anthony; Blom, Jochen; Bajic, Vladimir B.

    2015-01-01

    The OM43 clade within the family Methylophilaceae of Betaproteobacteria represents a group of methylotrophs that play important roles in the metabolism of C1 compounds in marine environments and other aquatic environments around the globe. Using dilution-to-extinction cultivation techniques, we successfully isolated a novel species of this clade (here designated MBRS-H7) from the ultraoligotrophic open ocean waters of the central Red Sea. Phylogenomic analyses indicate that MBRS-H7 is a novel species that forms a distinct cluster together with isolate KB13 from Hawaii (Hawaii-Red Sea [H-RS] cluster) that is separate from the cluster represented by strain HTCC2181 (from the Oregon coast). Phylogenetic analyses using the robust 16S-23S internal transcribed spacer revealed a potential ecotype separation of the marine OM43 clade members, which was further confirmed by metagenomic fragment recruitment analyses that showed trends of higher abundance in low-chlorophyll and/or high-temperature provinces for the H-RS cluster but a preference for colder, highly productive waters for the HTCC2181 cluster. This potential environmentally driven niche differentiation is also reflected in the metabolic gene inventories, which in the case of the H-RS cluster include those conferring resistance to high levels of UV irradiation, temperature, and salinity. Interestingly, we also found different energy conservation modules between these OM43 subclades, namely, the existence of the NADH:quinone oxidoreductase complex I (NUO) system in the H-RS cluster and the nonhomologous NADH:quinone oxidoreductase (NQR) system in the HTCC2181 cluster, which might have implications for their overall energetic yields. PMID:26655752

  7. Genome-Facilitated Analyses of Geomicrobial Processes

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth H. Nealson

    2012-05-02

    This project had the goal(s) of understanding the mechanism(s) of extracellular electron transport (EET) in the microbe Shewanella oneidensis MR-1, and a number of other strains and species in the genus Shewanella. The major accomplishments included sequencing, annotation, and analysis of more than 20 Shewanella genomes. The comparative genomics enabled the beginning of a systems biology approach to this genus. Another major contribution involved the study of gene regulation, primarily in the model organism, MR-1. As part of this work, we took advantage of special facilities at the DOE: e.g., the synchrotron radiation facility at ANL, where we successfully used this system for elemental characterization of single cells in different metabolic states (1). We began work with purified enzymes, and identification of partially purified enzymes, leading to initial characterization of several of the 42 c-type cytochromes from MR-1 (2). As the genome became annotated, we began experiments on transcriptome analysis under different conditions of growth, the first step towards systems biology (3,4). Conductive appendages of Shewanella, called bacterial nanowires were identified and characterized during this work (5, 11, 20,21). For the first time, it was possible to measure the electron transfer rate between single cells and a solid substrate (20), a rate that has been confirmed by several other laboratories. We also showed that MR-1 cells preferentially attach to cells at a given charge, and are not attracted, or even repelled by other charges. The interaction with the charged surfaces begins with a stimulation of motility (called electrokinesis), and eventually leads to attachment and growth. One of the things that genomics allows is the comparative analysis of the various Shewanella strains, which led to several important insights. First, while the genomes predicted that none of the strains looked like they should be able to degrade N-acetyl glucosamine (NAG), the monomer

  8. Analysis of health trait data from on-farm computer systems in the U.S. II: Comparison of genomic analyses including two-stage and single-step methods

    Science.gov (United States)

    The development of genomic selection methodology, with accompanying substantial gains in reliability for low-heritability traits, may dramatically improve the feasibility of genetic improvement of dairy cow health. Many methods for genomic analysis have now been developed, including the “Bayesian Al...

  9. Integrated genomic analyses of ovarian carcinoma

    NARCIS (Netherlands)

    Bell, D.; Berchuck, A.; Birrer, M.; Chien, J.; Dao, F.; Dhir, R.; DiSaia, P.; Gabra, H.; Glenn, P.; Godwin, A. K.; Gross, J.; Hartmann, L.; Huang, M.; Huntsman, D. G.; Iacocca, M.; Imielinski, M.; Kalloger, S.; Karlan, B. Y.; Levine, D. A.; Mills, G. B.; Morrison, C.; Mutch, D.; Olvera, N.; Orsulic, S.; Park, K.; Petrelli, N.; Rabeno, B.; Rader, J. S.; Sikic, B. I.; Smith-McCune, K.; Sood, A. K.; Bowtell, D.; Penny, R.; Testa, J. R.; Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Gunaratne, P.; Hawes, A. C.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Santibanez, J.; Reid, J. G.; Trevino, L. R.; Wu, Y. -Q.; Wang, M.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.; Getz, G.; Lawrence, M. S.; Cibulskis, K.; Sivachenko, A. Y.; Sougnez, C.; Voet, D.; Wilkinson, J.; Bloom, T.; Ardlie, K.; Fennell, T.; Baldwin, J.; Gabriel, S.; Lander, E. S.; Ding, L.; Fulton, R. S.; Koboldt, D. C.; McLellan, M. D.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D. J.; Fulton, L.; Abbott, R.; Dees, N. D.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C. C.; Schmidt, H.; Kalicki, J.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Cook, L.; Wallis, J. W.; Lin, L.; Magrini, V. J.; Hodges, J. S.; Eldred, J. M.; Smith, S. M.; Pohl, C. S.; Vandin, F.; Raphael, B. J.; Weinstock, G. M.; Mardis, R.; Wilson, R. K.; Meyerson, M.; Winckler, W.; Getz, G.; Verhaak, R. G. W.; Carter, S. L.; Mermel, C. H.; Saksena, G.; Nguyen, H.; Onofrio, R. C.; Lawrence, M. S.; Hubbard, D.; Gupta, S.; Crenshaw, A.; Ramos, A. H.; Ardlie, K.; Chin, L.; Protopopov, A.; Zhang, Juinhua; Kim, T. M.; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Sathiamoorthy, N.; Park, R. W.; Lee, E.; Park, P. J.; Kucherlapati, R.; Absher, D. M.; Waite, L.; Sherlock, G.; Brooks, J. D.; Li, J. Z.; Xu, J.; Myers, R. M.; Laird, P. W.; Cope, L.; Herman, J. G.; Shen, H.; Weisenberger, D. J.; Noushmehr, H.; Pan, F.; Triche, T.; Berman, B. P.; Van den Berg, D. J.; Buckley, J.; Baylin, S. B.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Jakkula, L. R.; Durinck, S.; Han, J.; Dorton, S.; Marr, H.; Choi, Y. G.; Wang, V.; Wang, N. J.; Ngai, J.; Conboy, J. G.; Parvin, B.; Feiler, H. S.; Speed, T. P.; Gray, J. W.; Levine, D. A.; Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Borsu, L.; Lash, A. E.; Brennan, C.; Viale, A.; Sander, C.; Ladanyi, M.; Hoadley, K. A.; Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y. J.; Zang, D.; Helms, E. B.; Balu, S.; Zhou, X.; Wu, J.; Topal, M. D.; Hayes, D. N.; Perou, C. M.; Getz, G.; Voet, D.; Saksena, G.; Zhang, Junihua; Zhang, H.; Wu, C. J.; Shukla, S.; Cibulskis, K.; Lawrence, M. S.; Sivachenko, A.; Jing, R.; Park, R. W.; Liu, Y.; Park, P. J.; Noble, M.; Chin, L.; Carter, H.; Kim, D.; Karchin, R.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Durinck, S.; Han, J.; Korkola, J. E.; Heiser, L. M.; Cho, R. J.; Hu, Z.; Parvin, B.; Speed, T. P.; Gray, J. W.; Schultz, N.; Cerami, E.; Taylor, B. S.; Olshen, A.; Reva, B.; Antipin, Y.; Shen, R.; Mankoo, P.; Sheridan, R.; Ciriello, G.; Chang, W. K.; Bernanke, J. A.; Borsu, L.; Levine, D. A.; Ladanyi, M.; Sander, C.; Haussler, D.; Benz, C. C.; Stuart, J. M.; Benz, S. C.; Sanborn, J. Z.; Vaske, C. J.; Zhu, J.; Szeto, C.; Scott, G. K.; Yau, C.; Hoadley, K. A.; Du, Y.; Balu, S.; Hayes, D. N.; Perou, C. M.; Wilkerson, M. D.; Zhang, N.; Akbani, R.; Baggerly, K. A.; Yung, W. K.; Mills, G. B.; Weinstein, J. N.; Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.; Kahn, A.; Greene, J. M.; Sfeir, R.; Jensen, M. A.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.; Zhang, Jinghui; Barker, A.; Compton, C.; Eley, G.; Ferguson, M.; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Shaw, K. R. Mills; Vaught, J.; Vockley, J. B.; Good, P. J.; Guyer, M. S.; Ozenberger, B.; Peterson, J.; Thomson, E.; Cramer, D.W.

    2011-01-01

    A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade

  10. PopGenome: an efficient Swiss army knife for population genomic analyses in R.

    Science.gov (United States)

    Pfeifer, Bastian; Wittelsbürger, Ulrich; Ramos-Onsins, Sebastian E; Lercher, Martin J

    2014-07-01

    Although many computer programs can perform population genetics calculations, they are typically limited in the analyses and data input formats they offer; few applications can process the large data sets produced by whole-genome resequencing projects. Furthermore, there is no coherent framework for the easy integration of new statistics into existing pipelines, hindering the development and application of new population genetics and genomics approaches. Here, we present PopGenome, a population genomics package for the R software environment (a de facto standard for statistical analyses). PopGenome can efficiently process genome-scale data as well as large sets of individual loci. It reads DNA alignments and single-nucleotide polymorphism (SNP) data sets in most common formats, including those used by the HapMap, 1000 human genomes, and 1001 Arabidopsis genomes projects. PopGenome also reads associated annotation files in GFF format, enabling users to easily define regions or classify SNPs based on their annotation; all analyses can also be applied to sliding windows. PopGenome offers a wide range of diverse population genetics analyses, including neutrality tests as well as statistics for population differentiation, linkage disequilibrium, and recombination. PopGenome is linked to Hudson's MS and Ewing's MSMS programs to assess statistical significance based on coalescent simulations. PopGenome's integration in R facilitates effortless and reproducible downstream analyses as well as the production of publication-quality graphics. Developers can easily incorporate new analyses methods into the PopGenome framework. PopGenome and R are freely available from CRAN (http://cran.r-project.org/) for all major operating systems under the GNU General Public License.

  11. Genomic analyses of the CAM plant pineapple.

    Science.gov (United States)

    Zhang, Jisen; Liu, Juan; Ming, Ray

    2014-07-01

    The innovation of crassulacean acid metabolism (CAM) photosynthesis in arid and/or low CO2 conditions is a remarkable case of adaptation in flowering plants. As the most important crop that utilizes CAM photosynthesis, the genetic and genomic resources of pineapple have been developed over many years. Genetic diversity studies using various types of DNA markers led to the reclassification of the two genera Ananas and Pseudananas and nine species into one genus Ananas and two species, A. comosus and A. macrodontes with five botanical varieties in A. comosus. Five genetic maps have been constructed using F1 or F2 populations, and high-density genetic maps generated by genotype sequencing are essential resources for sequencing and assembling the pineapple genome and for marker-assisted selection. There are abundant expression sequence tag resources but limited genomic sequences in pineapple. Genes involved in the CAM pathway has been analysed in several CAM plants but only a few of them are from pineapple. A reference genome of pineapple is being generated and will accelerate genetic and genomic research in this major CAM crop. This reference genome of pineapple provides the foundation for studying the origin and regulatory mechanism of CAM photosynthesis, and the opportunity to evaluate the classification of Ananas species and botanical cultivars.

  12. Bioinformatics tools for analysing viral genomic data.

    Science.gov (United States)

    Orton, R J; Gu, Q; Hughes, J; Maabar, M; Modha, S; Vattipally, S B; Wilkie, G S; Davison, A J

    2016-04-01

    The field of viral genomics and bioinformatics is experiencing a strong resurgence due to high-throughput sequencing (HTS) technology, which enables the rapid and cost-effective sequencing and subsequent assembly of large numbers of viral genomes. In addition, the unprecedented power of HTS technologies has enabled the analysis of intra-host viral diversity and quasispecies dynamics in relation to important biological questions on viral transmission, vaccine resistance and host jumping. HTS also enables the rapid identification of both known and potentially new viruses from field and clinical samples, thus adding new tools to the fields of viral discovery and metagenomics. Bioinformatics has been central to the rise of HTS applications because new algorithms and software tools are continually needed to process and analyse the large, complex datasets generated in this rapidly evolving area. In this paper, the authors give a brief overview of the main bioinformatics tools available for viral genomic research, with a particular emphasis on HTS technologies and their main applications. They summarise the major steps in various HTS analyses, starting with quality control of raw reads and encompassing activities ranging from consensus and de novo genome assembly to variant calling and metagenomics, as well as RNA sequencing.

  13. Diversity of Pseudomonas Genomes, Including Populus-Associated Isolates, as Revealed by Comparative Genome Analysis.

    Science.gov (United States)

    Jun, Se-Ran; Wassenaar, Trudy M; Nookaew, Intawat; Hauser, Loren; Wanchai, Visanu; Land, Miriam; Timm, Collin M; Lu, Tse-Yuan S; Schadt, Christopher W; Doktycz, Mitchel J; Pelletier, Dale A; Ussery, David W

    2015-10-30

    The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches, including the rhizosphere and endosphere of many plants. Their diversity influences the phylogenetic diversity and heterogeneity of these communities. On the basis of average amino acid identity, comparative genome analysis of >1,000 Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides (eastern cottonwood) trees resulted in consistent and robust genomic clusters with phylogenetic homogeneity. All Pseudomonas aeruginosa genomes clustered together, and these were clearly distinct from other Pseudomonas species groups on the basis of pangenome and core genome analyses. In contrast, the genomes of Pseudomonas fluorescens were organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. Most of our 21 Populus-associated isolates formed three distinct subgroups within the major P. fluorescens group, supported by pathway profile analysis, while two isolates were more closely related to Pseudomonas chlororaphis and Pseudomonas putida. Genes specific to Populus-associated subgroups were identified. Genes specific to subgroup 1 include several sensory systems that act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor. Genes specific to subgroup 2 contain hypothetical genes, and genes specific to subgroup 3 were annotated with hydrolase activity. This study justifies the need to sequence multiple isolates, especially from P. fluorescens, which displays the most genetic variation, in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.

  14. Genome size analyses of Pucciniales reveal the largest fungal genomes

    Directory of Open Access Journals (Sweden)

    Silvia eTavares

    2014-08-01

    Full Text Available Rust fungi (Basidiomycota, Pucciniales are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 151.5 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi. In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1,800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp. Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94 %. The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7,000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  15. Genomic sequencing and analyses of Lymantria xylina multiple nucleopolyhedrovirus

    Directory of Open Access Journals (Sweden)

    Lo Chu-Fang

    2010-02-01

    Full Text Available Abstract Background Outbreaks of the casuarina moth, Lymantria xylina Swinehoe (Lepidoptera: Lymantriidae, which is a very important forest pest in Taiwan, have occurred every five to 10 years. This moth has expanded its range of host plants to include more than 65 species of broadleaf trees. LyxyMNPV (L. xylina multiple nucleopolyhedrovirus is highly virulent to the casuarina moth and has been investigated as a possible biopesticide for controlling this moth. LdMNPV-like virus has also been isolated from Lymantria xylina larvae but LyxyMNPV was more virulent than LdMNPV-like virus both in NTU-LY and IPLB-LD-652Y cell lines. To better understand LyxyMNPV, the nucleotide sequence of the LyxyMNPV DNA genome was determined and analysed. Results The genome of LyxyMNPV consists of 156,344 bases, has a G+C content of 53.4% and contains 157 putative open reading frames (ORFs. The gene content and gene order of LyxyMNPV were similar to those of LdMNPV, with 151 ORFs identified as homologous to those reported in the LdMNPV genome. Two genes (Lyxy49 and Lyxy123 were homologous to other baculoviruses, and four unique LyxyMNPV ORFs (Lyxy11, Lyxy19, Lyxy130 and Lyxy131 were identified in the LyxyMNPV genome, including a gag-like gene that was not reported in baculoviruses. LdMNPV contains 23 ORFs that are absent in LyxyMNPV. Readily identifiable homologues of the gene host range factor-1 (hrf-1, which appears to be involved in the susceptibility of L. dispar to NPV infection, were not present in LyxyMNPV. Additionally, two putative odv-e27 homologues were identified in LyxyMNPV. The LyxyMNPV genome encoded 14 bro genes compared with 16 in LdMNPV, which occupied more than 8% of the LyxyMNPV genome. Thirteen homologous regions (hrs were identified containing 48 repeated sequences composed of 30-bp imperfect palindromes. However, they differed in the relative positions, number of repeats and orientation in the genome compared to LdMNPV. Conclusion The gene

  16. [Technological advances in single-cell genomic analyses].

    Science.gov (United States)

    Pan, Xing-Hua; Zhu, Hai-Ying; Marjani, Sadie L

    2011-01-01

    The technological progress of the genomics has transformed life science research. The main objectives of genomics are sequencing of new genomes and genome-wide identification of the function and the interaction of genes and their products. The recently developed second generation or next generation sequencing platforms and DNA microarray technology are immensely important and powerful tools for functional genomic analyses. However, their application is limited by the requirement of sufficient amounts of high quality nucleic acid samples. Therefore, when only a single cell or a very small number of cells are available or are preferred, the whole genomic sequencing or functional genomic objectives cannot be achieved conventionally and require a robust amplification method. This review highlights DNA amplification technologies and summarizes the strategies currently utilized for whole genome sequencing of a single cell, with specific focus on studies investigating microorganisms; An outline for targeted re-sequencing enabling the analysis of larger genomes is also provided. Furthermore, the review presents the emerging functional genomic applications using next-generation sequencing or microarray analysis to examine genome-wide transcriptional profile, chromatin modification and other types of protein-DNA binding profile, and CpG methylation mapping in a single cell or a very low quantity of cells. The nature of these technologies and their prospects are also addressed.

  17. Whole-Genome Analyses of lung function, height and smoking

    DEFF Research Database (Denmark)

    Janss, Luc; Sigsgaard, Torben; Sorensen, Daniel

    2014-01-01

    A joint analysis of FEV1 (forced expiratory volume after one second) and height is reported using novel methodology, as well as a single-trait analysis of smoking status. A first goal of the study was to incorporate dense genetic marker information in a random regression (Bayesian) model...... to quantify the relative contributions of genomic and environmental factors to the relationship between FEV1 and height. Smoking status was analysed using a probit random regression model and a second goal of the study was to estimate the genomic heritability of smoking status. Estimates of genomic...... heritabilities for height and FEV1 are equal to 0.47 and to 0.30, respectively. The estimates of the genomic and environmental correlations between height and FEV1 are 0.78 and 0.34, respectively. The posterior mean of the genomic heritability of smoking status is equal to 0.14 and provides evidence...

  18. Genomic and Transcriptomic Analyses of Foodborne Bacterial Pathogens

    Science.gov (United States)

    Zhang, Wei; Dudley, Edward G.; Wade, Joseph T.

    DNA microarrays (often interchangeably called DNA chips or DNA arrays) are among the most popular analytical tools for high-throughput comparative genomic and transcriptomic analyses of foodborne bacterial pathogens. A typical DNA microarray contains hundreds to millions of small DNA probes that are chemically attached (or "printed") onto the surface of a microscopic glass slide. Depending on the specific "printing" and probe synthesis technologies for different microarray platforms, such DNA probes can be PCR amplicons or in situ synthesized short oligonucleotides. DNA microarray technologies have revolutionized the way that we investigate the biology of foodborne bacterial pathogens. The major advantage of these technologies is that DNA microarrays allow comparison of subtle genomic or transcriptomic variations between two bacterial samples, such as genomic variations between two different bacterial strains or transcriptomic alterations of same bacterial strain under two different treatments. Some applications of comparative genomic hybridization microarrays and global gene expression microarrays have been covered in previous chapters of this book.

  19. Genome-wide transcription analyses in rice using tiling microarrays

    DEFF Research Database (Denmark)

    Li, Lei; Wang, Xiangfeng; Stolc, Viktor;

    2006-01-01

    Sequencing and computational annotation revealed several features, including high gene numbers, unusual composition of the predicted genes and a large number of genes lacking homology to known genes, that distinguish the rice (Oryza sativa) genome from that of other fully sequenced model species....... We report here a full-genome transcription analysis of the indica rice subspecies using high-density oligonucleotide tiling microarrays. Our results provided expression data support for the existence of 35,970 (81.9%) annotated gene models and identified 5,464 unique transcribed intergenic regions...... activity between duplicated segments of the genome. Collectively, our results provide the first whole-genome transcription map useful for further understanding the rice genome. Udgivelsesdato: 2006-Jan...

  20. Refining borders of genome-rearrangements including repetitions

    Directory of Open Access Journals (Sweden)

    JA Arjona-Medina

    2016-10-01

    Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.

  1. Quantitative metagenomic analyses based on average genome size normalization

    DEFF Research Database (Denmark)

    Frank, Jeremy Alexander; Sørensen, Søren Johannes

    2011-01-01

    Over the past quarter-century, microbiologists have used DNA sequence information to aid in the characterization of microbial communities. During the last decade, this has expanded from single genes to microbial community genomics, or metagenomics, in which the gene content of an environment can...... by estimating average genome sizes. This normalization can relieve comparative biases introduced by differences in community structure, number of sequencing reads, and sequencing read lengths between different metagenomes. We demonstrate the utility of this approach by comparing metagenomes from two different...... marine sources using both conventional small-subunit (SSU) rRNA gene analyses and our quantitative method to calculate the proportion of genomes in each sample that are capable of a particular metabolic trait. With both environments, to determine what proportion of each community they make up and how...

  2. Comparative Genomic and Phylogenomic Analyses Reveal a Conserved Core Genome Shared by Estuarine and Oceanic Cyanopodoviruses

    Science.gov (United States)

    Huang, Sijun; Zhang, Si; Jiao, Nianzhi; Chen, Feng

    2015-01-01

    Podoviruses are among the major viral groups that infect marine picocyanobacteria Prochlorococcus and Synechococcus. Here, we reported the genome sequences of five Synechococcus podoviruses isolated from the estuarine environment, and performed comparative genomic and phylogenomic analyses based on a total of 20 cyanopodovirus genomes. The genomes of all the known marine cyanopodoviruses are highly syntenic. A pan-genome of 349 clustered orthologous groups was determined, among which 15 were core genes. These core genes make up nearly half of each genome in length, reflecting the high level of genome conservation among this cyanophage type. The whole genome phylogenies based on concatenated core genes and gene content were highly consistent and confirmed the separation of two discrete marine cyanopodovirus clusters MPP-A and MPP-B. The genomes within cluster MPP-B grouped into subclusters mainly corresponding to Prochlorococcus or Synechococcus host types. Auxiliary metabolic genes tend to occur in a specific phylogenetic group of these cyanopodoviruses. All the MPP-B phages analyzed here encode the photosynthesis gene psbA, which are absent in all the MPP-A genomes thus far. Interestingly, all the MPP-B and two MPP-A Synechococcus podoviruses encode the thymidylate synthase gene thyX, while at the same genome locus all the MPP-B Prochlorococcus podoviruses encode the transaldolase gene talC. Both genes are hypothesized to have the potential to facilitate the biosynthesis of deoxynucleotide for phage replication. Inheritance of specific functional genes could be important to the evolution and ecological fitness of certain cyanophage genotypes. Our analyses demonstrate that cyanopodoviruses of estuarine and oceanic origins share a conserved core genome and suggest that accessory genes may be related to environmental adaptation. PMID:26569403

  3. Comparative Genomic and Phylogenomic Analyses Reveal a Conserved Core Genome Shared by Estuarine and Oceanic Cyanopodoviruses.

    Directory of Open Access Journals (Sweden)

    Sijun Huang

    Full Text Available Podoviruses are among the major viral groups that infect marine picocyanobacteria Prochlorococcus and Synechococcus. Here, we reported the genome sequences of five Synechococcus podoviruses isolated from the estuarine environment, and performed comparative genomic and phylogenomic analyses based on a total of 20 cyanopodovirus genomes. The genomes of all the known marine cyanopodoviruses are highly syntenic. A pan-genome of 349 clustered orthologous groups was determined, among which 15 were core genes. These core genes make up nearly half of each genome in length, reflecting the high level of genome conservation among this cyanophage type. The whole genome phylogenies based on concatenated core genes and gene content were highly consistent and confirmed the separation of two discrete marine cyanopodovirus clusters MPP-A and MPP-B. The genomes within cluster MPP-B grouped into subclusters mainly corresponding to Prochlorococcus or Synechococcus host types. Auxiliary metabolic genes tend to occur in a specific phylogenetic group of these cyanopodoviruses. All the MPP-B phages analyzed here encode the photosynthesis gene psbA, which are absent in all the MPP-A genomes thus far. Interestingly, all the MPP-B and two MPP-A Synechococcus podoviruses encode the thymidylate synthase gene thyX, while at the same genome locus all the MPP-B Prochlorococcus podoviruses encode the transaldolase gene talC. Both genes are hypothesized to have the potential to facilitate the biosynthesis of deoxynucleotide for phage replication. Inheritance of specific functional genes could be important to the evolution and ecological fitness of certain cyanophage genotypes. Our analyses demonstrate that cyanopodoviruses of estuarine and oceanic origins share a conserved core genome and suggest that accessory genes may be related to environmental adaptation.

  4. Quality control and conduct of genome-wide association meta-analyses

    DEFF Research Database (Denmark)

    Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C

    2014-01-01

    Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC...... at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide...

  5. Genomic and comparative genomic analyses of Rickettsia heilongjiangensis provide insight into its evolution and pathogenesis.

    Science.gov (United States)

    Duan, Changsong; Xiong, Xiaolu; Qi, Yong; Gong, Wenping; Jiao, Jun; Wen, Bohai

    2014-08-01

    Rickettsia heilongjiangensis, the causative agent of far eastern spotted fever, is an obligate intracellular gram-negative bacterium that belongs to the spotted fever group rickettsiae. To understand the evolution and pathogenesis of R. heilongjiangensis, we analyzed its genome and compared it with other rickettsial genomes available in GenBank. The R. heilongjiangensis chromosome contains 1333 genes, including 1297 protein coding genes and 36 RNA coding genes. The genome also contains 121 pseudogenes, 54 insertion sequences, and 39 tandem repeats. Sixteen genes encoding the major components of the type IV secretion systems were identified in the R. heilongjiangensis genome. In total, 37 β-barrel outer membrane proteins were predicted in the genome, eight of which have been previously confirmed to be outer membrane proteins. In addition, 266 potential virulence factor genes, seven partially deleted antibiotic resistance genes, and a genomic island were identified in the genome. The codon usage in the genome is compatible with its low GC content, and the amino acid usage shows apparent bias. A comparative genomic analysis showed that R. heilongjiangensis and R. japonica share one unique fragment that may be a target sequence for a diagnostic assay. The orthologs of 37 genes of R. heilongjiangensis were found in pathogenic R. rickettsii str. Sheila Smith but not in non-pathogenic R. rickettsii str. Iowa, which may explain why R. heilongjiangensis is pathogenic. Pan-genome analysis showed that R. heilongjiangensis and 42 other rickettsiae strains share 693 core genes with a pan-genome size of 4837 genes. The pan-genome-based phylogeny showed that R. heilongjiangensis was closely related to R. japonica.

  6. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    Science.gov (United States)

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  7. The geometric increase in meta-analyses from China in the genomic era.

    Directory of Open Access Journals (Sweden)

    John P A Ioannidis

    Full Text Available Meta-analyses are increasingly popular. It is unknown whether this popularity is driven by specific countries and specific meta-analyses types. PubMed was used to identify meta-analyses since 1995 (last update 9/1/2012 and catalogue their types and country of origin. We focused more on meta-analyses from China (the current top producer of meta-analyses versus the USA (top producer until recently. The annual number of meta-analyses from China increased 40-fold between 2003 and 2011 versus 2.4-fold for the USA. The growth of Chinese meta-analyses was driven by genetics (110-fold increase in 2011 versus 2003. The HuGE Navigator identified 612 meta-analyses of genetic association studies published in 2012 from China versus only 109 from the USA. We compared in-depth 50 genetic association meta-analyses from China versus 50 from USA in 2012. Meta-analyses from China almost always used only literature-based data (92%, and focused on one or two genes (94% and variants (78% identified with candidate gene approaches (88%, while many USA meta-analyses used genome-wide approaches and raw data. Both groups usually concluded favorably for the presence of genetic associations (80% versus 74%, but nominal significance (P<0.05 typically sufficed in the China group. Meta-analyses from China typically neglected genome-wide data, and often included candidate gene studies published in Chinese-language journals. Overall, there is an impressive rise of meta-analyses from China, particularly on genetic associations. Since most claimed candidate gene associations are likely false-positives, there is an urgent global need to incorporate genome-wide data and state-of-the art statistical inferences to avoid a flood of false-positive genetic meta-analyses.

  8. The geometric increase in meta-analyses from China in the genomic era.

    Science.gov (United States)

    Ioannidis, John P A; Chang, Christine Q; Lam, Tram Kim; Schully, Sheri D; Khoury, Muin J

    2013-01-01

    Meta-analyses are increasingly popular. It is unknown whether this popularity is driven by specific countries and specific meta-analyses types. PubMed was used to identify meta-analyses since 1995 (last update 9/1/2012) and catalogue their types and country of origin. We focused more on meta-analyses from China (the current top producer of meta-analyses) versus the USA (top producer until recently). The annual number of meta-analyses from China increased 40-fold between 2003 and 2011 versus 2.4-fold for the USA. The growth of Chinese meta-analyses was driven by genetics (110-fold increase in 2011 versus 2003). The HuGE Navigator identified 612 meta-analyses of genetic association studies published in 2012 from China versus only 109 from the USA. We compared in-depth 50 genetic association meta-analyses from China versus 50 from USA in 2012. Meta-analyses from China almost always used only literature-based data (92%), and focused on one or two genes (94%) and variants (78%) identified with candidate gene approaches (88%), while many USA meta-analyses used genome-wide approaches and raw data. Both groups usually concluded favorably for the presence of genetic associations (80% versus 74%), but nominal significance (PChina group. Meta-analyses from China typically neglected genome-wide data, and often included candidate gene studies published in Chinese-language journals. Overall, there is an impressive rise of meta-analyses from China, particularly on genetic associations. Since most claimed candidate gene associations are likely false-positives, there is an urgent global need to incorporate genome-wide data and state-of-the art statistical inferences to avoid a flood of false-positive genetic meta-analyses.

  9. Genomic and phylogenetic analyses of murine adenovirus 2.

    Science.gov (United States)

    Hemmi, Silvio; Vidovszky, Márton Z; Ruminska, Justyna; Ramelli, Sandra; Decurtins, Willy; Greber, Urs F; Harrach, Balázs

    2011-09-01

    Murine adenoviruses (MAdV) are supposedly the oldest members of the genus Mastadenovirus. Currently, there are three distinct MAdV types known with rather different tropism and pathology. Here we report and annotate the DNA sequence of the full genome of MAdV-2. It was found to consist of 35,203 bp thus being considerably larger than the genomes of the other two MAdV types. The increased size of the MAdV-2 genome is generally due to larger genes and ORFs, although some differences in the number of ORFs were observed for the early regions E1, E3 and E4. The homologue of the 19K gene of E1B from MAdV-2 codes for 330 amino acids (aa) and is almost twice as large as from other mastadenoviruses. Accordingly, only the N-terminal half (155aa) has homology to the 19K protein. A homologue of the gene of the 12.5K protein was identified in the E3 region of MAdV-2, but not in MAdV-1 or MAdV-3. The other gene of yet unknown function in the E3 region of MAdV-2 seems to be unique. The E4 region of MAdV-2 contains three ORFs. One has similarity to the 34K gene of other AdVs. Two unique ORFs in the E4 region of MAdV-2 have no homology to any of the five and six ORFs in the E4 region of MAdV-1 or MAdV-3, respectively. Phylogenetic analyses showed that the three murine AdVs have a close common ancestor. They likely formed the first branching of the lineage of mastadenoviruses, and seem to be the most ancient representatives of this genus. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Genome-wide analyses of small noncoding RNAs in streptococci

    Directory of Open Access Journals (Sweden)

    Nadja ePatenge

    2015-05-01

    Full Text Available Streptococci represent a diverse group of Gram-positive bacteria, which colonize a wide range of hosts among animals and humans. Streptococcal species occur as commensal as well as pathogenic organisms. Many of the pathogenic species can cause severe, invasive infections in their hosts leading to a high morbidity and mortality. The consequence is a tremendous suffering on the part of men and livestock besides the significant financial burden in the agricultural and healthcare sectors. An environmentally stimulated and tightly controlled expression of virulence factor genes is of fundamental importance for streptococcal pathogenicity. Bacterial small noncoding RNAs (sRNAs modulate the expression of genes involved in stress response, sugar metabolism, surface composition, and other properties that are related to bacterial virulence. Even though the regulatory character is shared by this class of RNAs, variation on the molecular level results in a high diversity of functional mechanisms. The knowledge about the role of sRNAs in streptococci is still limited, but in recent years, genome-wide screens for sRNAs have been conducted in an increasing number of species. Bioinformatics prediction approaches have been employed as well as expression analyses by classical array techniques or next generation sequencing. This review will give an overview of whole genome screens for sRNAs in streptococci with a focus on describing the different methods and comparing their outcome considering sRNA conservation among species, functional similarities, and relevance for streptococcal infection.

  11. Genome-wide methylation analyses in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Rose K Lai

    Full Text Available Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM. Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina were used to interrogate 26,486 informative CpG sites in both the discovery and validation datasets. Global methylation levels were assessed by analysis of L1 retrotransposon (LINE1, 5 methyl-deoxycytidine (5m-dC and 5 hydroxylmethyl-deoxycytidine (5hm-dC in the discovery dataset. We validated a total of 1548 CpG sites (1307 genes that were differentially methylated in GBM compared to controls. There were more than twice as many hypomethylated genes as hypermethylated ones. Both the discovery and validation datasets found 5 tumor methylation classes. Pathway analyses showed that the top ten pathways in hypomethylated genes were all related to functions of innate and acquired immunities. Among hypermethylated pathways, transcriptional regulatory network in embryonic stem cells was the most significant. In the study of global methylation markers, 5m-dC level was the best discriminant among methylation classes, whereas in survival analyses, high level of LINE1 methylation was an independent, favorable prognostic factor in the discovery dataset. Based on a pathway approach, hypermethylation in genes that control stem cell differentiation were significant, poor prognostic factors of overall survival in both the discovery and validation datasets. Approaches that targeted these methylated genes may be a future therapeutic goal.

  12. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

    Directory of Open Access Journals (Sweden)

    Pengpeng Li

    Full Text Available S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

  13. Genome mining expands the chemical diversity of the cyanobactin family to include highly modified linear peptides.

    Science.gov (United States)

    Leikoski, Niina; Liu, Liwei; Jokela, Jouni; Wahlsten, Matti; Gugger, Muriel; Calteau, Alexandra; Permi, Perttu; Kerfeld, Cheryl A; Sivonen, Kaarina; Fewer, David P

    2013-08-22

    Ribosomal peptides are produced through the posttranslational modification of short precursor peptides. Cyanobactins are a growing family of cyclic ribosomal peptides produced by cyanobacteria. However, a broad systematic survey of the genetic capacity to produce cyanobactins is lacking. Here we report the identification of 31 cyanobactin gene clusters from 126 genomes of cyanobacteria. Genome mining suggested a complex evolutionary history defined by horizontal gene transfer and rapid diversification of precursor genes. Extensive chemical analyses demonstrated that some cyanobacteria produce short linear cyanobactins with a chain length ranging from three to five amino acids. The linear peptides were N-prenylated and O-methylated on the N and C termini, respectively, and named aeruginosamide and viridisamide. These findings broaden the structural diversity of the cyanobactin family to include highly modified linear peptides with rare posttranslational modifications.

  14. 78 FR 26847 - Including Specific Pavement Types in Federal-aid Highway Traffic Noise Analyses

    Science.gov (United States)

    2013-05-08

    ... Federal Highway Administration Including Specific Pavement Types in Federal-aid Highway Traffic Noise... types used in Federal-aid highway traffic noise analyses. Current highway traffic noise analyses rely on... suggestions on whether and how to include additional pavement types in Federal-aid highway traffic...

  15. Comparative genomic and phylogenomic analyses of the Bifidobacteriaceae family

    National Research Council Canada - National Science Library

    Gabriele Andrea Lugli; Christian Milani; Francesca Turroni; Sabrina Duranti; Leonardo Mancabelli; Marta Mangifesta; Chiara Ferrario; Monica Modesto; Paola Mattarelli; Killer Jiři; Douwe van Sinderen; Marco Ventura

    2017-01-01

    ... they also occur as pathogenic bacteria of the urogenital tract. The pan-genome of the genus Bifidobacterium has been explored in detail in recent years, though genomics of the Bifidobacteriaceae family has not yet received much attention...

  16. Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review

    Directory of Open Access Journals (Sweden)

    Timor Faber

    2016-03-01

    Full Text Available Abstract Background There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation. We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions. Methods For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta-analyses including at least one non-randomized study evaluating therapeutic interventions. Etiological assessments and meta-analyses with no comparison group were excluded. Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta-analysis methods. Results One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs and non-randomized studies of interventions (NRSI and 69 only NRSI. Half of the meta-analyses (n = 92, 49 % evaluated non-pharmacological interventions. “Grey literature” was searched for 72 meta-analyses (38 %. An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72 % but this assessment considered the risk of confounding bias in only 33 meta-analyses (18 %. In 130 meta-analyses (69 %, the design of each NRSI was not clearly specified. In 131 (70 %, whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported. Heterogeneity across studies was assessed in 182 meta-analyses (97 % and further explored in 157 (84 %. Reporting bias was assessed in 127 (68 %. Conclusions Some key methodological components of the systematic review process—search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined—are not adequately carried out or reported in meta-analyses including NRSI.

  17. Genomic analyses inform on migration events during the peopling of Eurasia

    Science.gov (United States)

    Pagani, Luca; Lawson, Daniel John; Jagoda, Evelyn; Mörseburg, Alexander; Eriksson, Anders; Mitt, Mario; Clemente, Florian; Hudjashov, Georgi; Degiorgio, Michael; Saag, Lauri; Wall, Jeffrey D.; Cardona, Alexia; Mägi, Reedik; Sayres, Melissa A. Wilson; Kaewert, Sarah; Inchley, Charlotte; Scheib, Christiana L.; Järve, Mari; Karmin, Monika; Jacobs, Guy S.; Antao, Tiago; Iliescu, Florin Mircea; Kushniarevich, Alena; Ayub, Qasim; Tyler-Smith, Chris; Xue, Yali; Yunusbayev, Bayazit; Tambets, Kristiina; Mallick, Chandana Basu; Saag, Lehti; Pocheshkhova, Elvira; Andriadze, George; Muller, Craig; Westaway, Michael C.; Lambert, David M.; Zoraqi, Grigor; Turdikulova, Shahlo; Dalimova, Dilbar; Sabitov, Zhaxylyk; Sultana, Gazi Nurun Nahar; Lachance, Joseph; Tishkoff, Sarah; Momynaliev, Kuvat; Isakova, Jainagul; Damba, Larisa D.; Gubina, Marina; Nymadawa, Pagbajabyn; Evseeva, Irina; Atramentova, Lubov; Utevska, Olga; Ricaut, François-Xavier; Brucato, Nicolas; Sudoyo, Herawati; Letellier, Thierry; Cox, Murray P.; Barashkov, Nikolay A.; Škaro, Vedrana; Mulahasano´, Lejla; Primorac, Dragan; Sahakyan, Hovhannes; Mormina, Maru; Eichstaedt, Christina A.; Lichman, Daria V.; Abdullah, Syafiq; Chaubey, Gyaneshwer; Wee, Joseph T. S.; Mihailov, Evelin; Karunas, Alexandra; Litvinov, Sergei; Khusainova, Rita; Ekomasova, Natalya; Akhmetova, Vita; Khidiyatova, Irina; Marjanović, Damir; Yepiskoposyan, Levon; Behar, Doron M.; Balanovska, Elena; Metspalu, Andres; Derenko, Miroslava; Malyarchuk, Boris; Voevoda, Mikhail; Fedorova, Sardana A.; Osipova, Ludmila P.; Lahr, Marta Mirazón; Gerbault, Pascale; Leavesley, Matthew; Migliano, Andrea Bamberg; Petraglia, Michael; Balanovsky, Oleg; Khusnutdinova, Elza K.; Metspalu, Ene; Thomas, Mark G.; Manica, Andrea; Nielsen, Rasmus; Villems, Richard; Willerslev, Eske; Kivisild, Toomas; Metspalu, Mait

    2016-10-01

    High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.

  18. Genomic analyses inform on migration events during the peopling of Eurasia

    KAUST Repository

    Pagani, Luca

    2016-09-20

    High-Coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long-and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago. © 2016 Macmillan Publishers Limited, part of Springer Nature.

  19. Genome-wide analyses of HTLV-1aD strains from Cape Verde, Africa

    Science.gov (United States)

    Zanella, Louise; de Pina-Araujo I, Isabel; Morgado, Mariza G; Vicente, Ana Carolina

    2016-01-01

    We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution. PMID:27653363

  20. Genomic Analyses of Bacterial Porin-Cytochrome Gene Clusters

    Directory of Open Access Journals (Sweden)

    Liang eShi

    2014-11-01

    Full Text Available The porin-cytochrome (Pcc protein complex is responsible for trans-outer membrane electron transfer during extracellular reduction of Fe(III by the dissimilatory metal-reducing bacterium Geobacter sulfurreducens PCA. The identified and characterized Pcc complex of G. sulfurreducens PCA consists of a porin-like outer-membrane protein, a periplasmic 8-heme c-type cytochrome (c-Cyt and an outer-membrane 12-heme c-Cyt, and the genes encoding the Pcc proteins are clustered in the same regions of genome (i.e., the pcc gene clusters of G. sulfurreducens PCA. A survey of additionally microbial genomes has identified the pcc gene clusters in all sequenced Geobacter spp. and other bacteria from six different phyla, including Anaeromyxobacter dehalogenans 2CP-1, A. dehalogenans 2CP-C, Anaeromyxobacter sp. K, Candidatus Kuenenia stuttgartiensis, Denitrovibrio acetiphilus DSM 12809, Desulfurispirillum indicum S5, Desulfurivibrio alkaliphilus AHT2, Desulfurobacterium thermolithotrophum DSM 11699, Desulfuromonas acetoxidans DSM 684, Ignavibacterium album JCM 16511, and Thermovibrio ammonificans HB-1. The numbers of genes in the pcc gene clusters vary, ranging from two to nine. Similar to the metal-reducing (Mtr gene clusters of other Fe(III-reducing bacteria, such as Shewanella spp., additional genes that encode putative c-Cyts with predicted cellular localizations at the cytoplasmic membrane, periplasm and outer membrane often associate with the pcc gene clusters. This suggests that the Pcc-associated c-Cyts may be part of the pathways for extracellular electron transfer reactions. The presence of pcc gene clusters in the microorganisms that do not reduce solid-phase Fe(III and Mn(IV oxides, such as D. alkaliphilus AHT2 and I. album JCM 16511, also suggests that some of the pcc gene clusters may be involved in extracellular electron transfer reactions with the substrates other than Fe(III and Mn(IV oxides.

  1. Mitochondrial genome analyses suggest multiple Trichuris species in humans, baboons, and pigs from different geographical regions

    DEFF Research Database (Denmark)

    Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.;

    2015-01-01

    BACKGROUND: The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found...... in primates. METHODS AND FINDINGS: We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes...... of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively...

  2. High performance computation of landscape genomic models including local indicators of spatial association.

    Science.gov (United States)

    Stucki, S; Orozco-terWengel, P; Forester, B R; Duruz, S; Colli, L; Masembe, C; Negrini, R; Landguth, E; Jones, M R; Bruford, M W; Taberlet, P; Joost, S

    2016-11-01

    With the increasing availability of both molecular and topo-climatic data, the main challenges facing landscape genomics - that is the combination of landscape ecology with population genomics - include processing large numbers of models and distinguishing between selection and demographic processes (e.g. population structure). Several methods address the latter, either by estimating a null model of population history or by simultaneously inferring environmental and demographic effects. Here we present samβada, an approach designed to study signatures of local adaptation, with special emphasis on high performance computing of large-scale genetic and environmental data sets. samβada identifies candidate loci using genotype-environment associations while also incorporating multivariate analyses to assess the effect of many environmental predictor variables. This enables the inclusion of explanatory variables representing population structure into the models to lower the occurrences of spurious genotype-environment associations. In addition, samβada calculates local indicators of spatial association for candidate loci to provide information on whether similar genotypes tend to cluster in space, which constitutes a useful indication of the possible kinship between individuals. To test the usefulness of this approach, we carried out a simulation study and analysed a data set from Ugandan cattle to detect signatures of local adaptation with samβada, bayenv, lfmm and an FST outlier method (FDIST approach in arlequin) and compare their results. samβada - an open source software for Windows, Linux and Mac OS X available at http://lasig.epfl.ch/sambada - outperforms other approaches and better suits whole-genome sequence data processing.

  3. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  4. Quasispecies Analyses of the HIV-1 Near-full-length Genome With Illumina MiSeq.

    Science.gov (United States)

    Ode, Hirotaka; Matsuda, Masakazu; Matsuoka, Kazuhiro; Hachiya, Atsuko; Hattori, Junko; Kito, Yumiko; Yokomaku, Yoshiyuki; Iwatani, Yasumasa; Sugiura, Wataru

    2015-01-01

    Human immunodeficiency virus type-1 (HIV-1) exhibits high between-host genetic diversity and within-host heterogeneity, recognized as quasispecies. Because HIV-1 quasispecies fluctuate in terms of multiple factors, such as antiretroviral exposure and host immunity, analyzing the HIV-1 genome is critical for selecting effective antiretroviral therapy and understanding within-host viral coevolution mechanisms. Here, to obtain HIV-1 genome sequence information that includes minority variants, we sought to develop a method for evaluating quasispecies throughout the HIV-1 near-full-length genome using the Illumina MiSeq benchtop deep sequencer. To ensure the reliability of minority mutation detection, we applied an analysis method of sequence read mapping onto a consensus sequence derived from de novo assembly followed by iterative mapping and subsequent unique error correction. Deep sequencing analyses of aHIV-1 clone showed that the analysis method reduced erroneous base prevalence below 1% in each sequence position and discarded only 1%-frequency sequences throughout the genome. When we evaluated sequences of pol genes from 18 treatment-naïve patients' samples, the deep sequencing results were in agreement with Sanger sequencing and identified numerous additional minority mutations. The results suggest that our deep sequencing method would be suitable for identifying within-host viral population dynamics throughout the genome.

  5. Genomic analyses provide insights into the history of tomato breeding.

    Science.gov (United States)

    Lin, Tao; Zhu, Guangtao; Zhang, Junhong; Xu, Xiangyang; Yu, Qinghui; Zheng, Zheng; Zhang, Zhonghua; Lun, Yaoyao; Li, Shuai; Wang, Xiaoxuan; Huang, Zejun; Li, Junming; Zhang, Chunzhi; Wang, Taotao; Zhang, Yuyang; Wang, Aoxue; Zhang, Yancong; Lin, Kui; Li, Chuanyou; Xiong, Guosheng; Xue, Yongbiao; Mazzucato, Andrea; Causse, Mathilde; Fei, Zhangjun; Giovannoni, James J; Chetelat, Roger T; Zamir, Dani; Städler, Thomas; Li, Jingfu; Ye, Zhibiao; Du, Yongchen; Huang, Sanwen

    2014-11-01

    The histories of crop domestication and breeding are recorded in genomes. Although tomato is a model species for plant biology and breeding, the nature of human selection that altered its genome remains largely unknown. Here we report a comprehensive analysis of tomato evolution based on the genome sequences of 360 accessions. We provide evidence that domestication and improvement focused on two independent sets of quantitative trait loci (QTLs), resulting in modern tomato fruit ∼100 times larger than its ancestor. Furthermore, we discovered a major genomic signature for modern processing tomatoes, identified the causative variants that confer pink fruit color and precisely visualized the linkage drag associated with wild introgressions. This study outlines the accomplishments as well as the costs of historical selection and provides molecular insights toward further improvement.

  6. Comprehensive analyses of genomes, transcriptomes and metabolites of neem tree

    Directory of Open Access Journals (Sweden)

    Nagesh A. Kuravadi

    2015-08-01

    Full Text Available Neem (Azadirachta indica A. Juss is one of the most versatile tropical evergreen tree species known in India since the Vedic period (1500 BC–600 BC. Neem tree is a rich source of limonoids, having a wide spectrum of activity against insect pests and microbial pathogens. Complex tetranortriterpenoids such as azadirachtin, salanin and nimbin are the major active principles isolated from neem seed. Absolutely nothing is known about the biochemical pathways of these metabolites in neem tree. To identify genes and pathways in neem, we sequenced neem genomes and transcriptomes using next generation sequencing technologies. Assembly of Illumina and 454 sequencing reads resulted in 267 Mb, which accounts for 70% of estimated size of neem genome. We predicted 44,495 genes in the neem genome, of which 32,278 genes were expressed in neem tissues. Neem genome consists about 32.5% (87 Mb of repetitive DNA elements. Neem tree is phylogenetically related to citrus, Citrus sinensis. Comparative analysis anchored 62% (161 Mb of assembled neem genomic contigs onto citrus chromomes. Ultrahigh performance liquid chromatography-mass spectrometry-selected reaction monitoring (UHPLC-MS/SRM method was used to quantify azadirachtin, nimbin, and salanin from neem tissues. Weighted Correlation Network Analysis (WCGNA of expressed genes and metabolites resulted in identification of possible candidate genes involved in azadirachtin biosynthesis pathway. This study provides genomic, transcriptomic and quantity of top three neem metabolites resource, which will accelerate basic research in neem to understand biochemical pathways.

  7. Comprehensive analyses of genomes, transcriptomes and metabolites of neem tree.

    Science.gov (United States)

    Kuravadi, Nagesh A; Yenagi, Vijay; Rangiah, Kannan; Mahesh, H B; Rajamani, Anantharamanan; Shirke, Meghana D; Russiachand, Heikham; Loganathan, Ramya Malarini; Shankara Lingu, Chandana; Siddappa, Shilpa; Ramamurthy, Aishwarya; Sathyanarayana, B N; Gowda, Malali

    2015-01-01

    Neem (Azadirachta indica A. Juss) is one of the most versatile tropical evergreen tree species known in India since the Vedic period (1500 BC-600 BC). Neem tree is a rich source of limonoids, having a wide spectrum of activity against insect pests and microbial pathogens. Complex tetranortriterpenoids such as azadirachtin, salanin and nimbin are the major active principles isolated from neem seed. Absolutely nothing is known about the biochemical pathways of these metabolites in neem tree. To identify genes and pathways in neem, we sequenced neem genomes and transcriptomes using next generation sequencing technologies. Assembly of Illumina and 454 sequencing reads resulted in 267 Mb, which accounts for 70% of estimated size of neem genome. We predicted 44,495 genes in the neem genome, of which 32,278 genes were expressed in neem tissues. Neem genome consists about 32.5% (87 Mb) of repetitive DNA elements. Neem tree is phylogenetically related to citrus, Citrus sinensis. Comparative analysis anchored 62% (161 Mb) of assembled neem genomic contigs onto citrus chromomes. Ultrahigh performance liquid chromatography-mass spectrometry-selected reaction monitoring (UHPLC-MS/SRM) method was used to quantify azadirachtin, nimbin, and salanin from neem tissues. Weighted Correlation Network Analysis (WCGNA) of expressed genes and metabolites resulted in identification of possible candidate genes involved in azadirachtin biosynthesis pathway. This study provides genomic, transcriptomic and quantity of top three neem metabolites resource, which will accelerate basic research in neem to understand biochemical pathways.

  8. GEMBASSY: an EMBOSS associated software package for comprehensive genome analyses.

    Science.gov (United States)

    Itaya, Hidetoshi; Oshita, Kazuki; Arakawa, Kazuharu; Tomita, Masaru

    2013-08-29

    The popular European Molecular Biology Open Software Suite (EMBOSS) currently contains over 400 tools used in various bioinformatics researches, equipped with sophisticated development frameworks for interoperability and tool discoverability as well as rich documentations and various user interfaces. In order to further strengthen EMBOSS in the fields of genomics, we here present a novel EMBOSS associated software (EMBASSY) package named GEMBASSY, which adds more than 50 analysis tools from the G-language Genome Analysis Environment and its Representational State Transfer (REST) and SOAP web services. GEMBASSY basically contains wrapper programs of G-language REST/SOAP web services to provide intuitive and easy access to various annotations within complete genome flatfiles, as well as tools for analyzing nucleic composition, calculating codon usage, and visualizing genomic information. For example, analysis methods such as for calculating distance between sequences by genomic signatures and for predicting gene expression levels from codon usage bias are effective in the interpretation of meta-genomic and meta-transcriptomic data. GEMBASSY tools can be used seamlessly with other EMBOSS tools and UNIX command line tools. The source code written in C is available from GitHub (https://github.com/celery-kotone/GEMBASSY/) and the distribution package is freely available from the GEMBASSY web site (http://www.g-language.org/gembassy/).

  9. Genomic and Systems Biology Analyses of Social Behavior or Evolutionary Genomic Analyses of Insect Society: Eat, Drink, and Be Scary (2011 JGI User Meeting)

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Gene

    2011-03-23

    The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Gene Robinson of the University of Illinois on "Genomic and Systems Biology Analyses of Social Behavior" at the 6th Annual Genomics of Energy & Environment Meeting on March 23, 2011

  10. The Genomic Scrapheap Challenge; Extracting Relevant Data from Unmapped Whole Genome Sequencing Reads, Including Strain Specific Genomic Segments, in Rats.

    Science.gov (United States)

    van der Weide, Robin H; Simonis, Marieke; Hermsen, Roel; Toonen, Pim; Cuppen, Edwin; de Ligt, Joep

    2016-01-01

    Unmapped next-generation sequencing reads are typically ignored while they contain biologically relevant information. We systematically analyzed unmapped reads from whole genome sequencing of 33 inbred rat strains. High quality reads were selected and enriched for biologically relevant sequences; similarity-based analysis revealed clustering similar to previously reported phylogenetic trees. Our results demonstrate that on average 20% of all unmapped reads harbor sequences that can be used to improve reference genomes and generate hypotheses on potential genotype-phenotype relationships. Analysis pipelines would benefit from incorporating the described methods and reference genomes would benefit from inclusion of the genomic segments obtained through these efforts.

  11. Mutation analyses of integrated HBV genome in hepatitis B patients

    Institute of Scientific and Technical Information of China (English)

    Peilin Wang; Xiuhai Wang; Shuying Cong; Hongming Ma; Xuecheng Zhang

    2008-01-01

    Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBF, and in peripheral blood mononuclear cells (PBMC) from 74 cases of HBFs and their children who were born after their fathers' HBV infection (caHBF). We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBF. It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBF. This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

  12. Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates.

    Directory of Open Access Journals (Sweden)

    Bo Yuan

    2015-12-01

    Full Text Available Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100 is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases-about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual's susceptibility to acquiring disease-associated alleles.

  13. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

    Directory of Open Access Journals (Sweden)

    Ahmed Idbaih

    Full Text Available Anaplastic oligodendrogliomas (AOD are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19(q10;p10, IDH1, IDH2, CIC and FUBP1 mutations.To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA," has been supported by the Institut National du Cancer (InCA. Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

  14. GEMBASSY: an EMBOSS associated software package for comprehensive genome analyses

    OpenAIRE

    Itaya, Hidetoshi; Oshita, Kazuki; Arakawa, Kazuharu; Tomita, Masaru

    2013-01-01

    The popular European Molecular Biology Open Software Suite (EMBOSS) currently contains over 400 tools used in various bioinformatics researches, equipped with sophisticated development frameworks for interoperability and tool discoverability as well as rich documentations and various user interfaces. In order to further strengthen EMBOSS in the fields of genomics, we here present a novel EMBOSS associated software (EMBASSY) package named GEMBASSY, which adds more than 50 analysis tools from t...

  15. Impact of chromatin structures on DNA processing for genomic analyses.

    Directory of Open Access Journals (Sweden)

    Leonid Teytelman

    Full Text Available Chromatin has an impact on recombination, repair, replication, and evolution of DNA. Here we report that chromatin structure also affects laboratory DNA manipulation in ways that distort the results of chromatin immunoprecipitation (ChIP experiments. We initially discovered this effect at the Saccharomyces cerevisiae HMR locus, where we found that silenced chromatin was refractory to shearing, relative to euchromatin. Using input samples from ChIP-Seq studies, we detected a similar bias throughout the heterochromatic portions of the yeast genome. We also observed significant chromatin-related effects at telomeres, protein binding sites, and genes, reflected in the variation of input-Seq coverage. Experimental tests of candidate regions showed that chromatin influenced shearing at some loci, and that chromatin could also lead to enriched or depleted DNA levels in prepared samples, independently of shearing effects. Our results suggested that assays relying on immunoprecipitation of chromatin will be biased by intrinsic differences between regions packaged into different chromatin structures - biases which have been largely ignored to date. These results established the pervasiveness of this bias genome-wide, and suggested that this bias can be used to detect differences in chromatin structures across the genome.

  16. ETS-Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0385 TITLE: ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression...29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0385 ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect...upregulation of ERG, a transcription factor with oncogenic roles in other cancers such as leukemias and sarcomas (Tomlins, Rhodes et al. 2005; Turner

  17. Identification of the most informative regions of the mitochondrial genome for phylogenetic and coalescent analyses.

    Science.gov (United States)

    Non, A L; Kitchen, A; Mulligan, C J

    2007-09-01

    Analysis of complete mitochondrial genome sequences is becoming increasingly common in genetic studies. The availability of full genome datasets enables an analysis of the information content distributed throughout the mitochondrial genome in order to optimize the research design of future evolutionary studies. The goal of our study was to identify informative regions of the human mitochondrial genome using two criteria: (1) accurate reconstruction of a phylogeny and (2) consistent estimates of time to most recent common ancestor (TMRCA). We created two series of datasets by deleting individual genes of varied length and by deleting 10 equal-size fragments throughout the coding region. Phylogenies were statistically compared to the full-coding-region tree, while coalescent methods were used to estimate the TMRCA and associated credible intervals. Individual fragments important for maintaining a phylogeny similar to the full-coding-region tree encompassed bp 577-2122 and 11,399-16,023, including all or part of 12S rRNA, 16S rRNA, ND4, ND5, ND6, and cytb. The control region only tree was the most poorly resolved with the majority of the tree manifest as an unresolved polytomy. Coalescent estimates of TMRCA were less sensitive to removal of any particular fragment(s) than reconstruction of a consistent phylogeny. Overall, we discovered that half the genome, i.e., bp 3669-11,398, could be removed with no significant change in the phylogeny (p(AU)=0.077) while still maintaining overlap of TMRCA 95% credible intervals. Thus, sequencing a contiguous fragment from bp 11,399 through the control region to bp 3668 would create a dataset that optimizes the information necessary for phylogenetic and coalescent analyses and also takes advantage of the wealth of data already available on the control region.

  18. Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae

    Science.gov (United States)

    2012-01-01

    Background Staphylococcus belongs to the Gram-positive low G + C content group of the Firmicutes division of bacteria. Staphylococcus aureus is an important human and veterinary pathogen that causes a broad spectrum of diseases, and has developed important multidrug resistant forms such as methicillin-resistant S. aureus (MRSA). Staphylococcus simiae was isolated from South American squirrel monkeys in 2000, and is a coagulase-negative bacterium, closely related, and possibly the sister group, to S. aureus. Comparative genomic analyses of closely related bacteria with different phenotypes can provide information relevant to understanding adaptation to host environment and mechanisms of pathogenicity. Results We determined a Roche/454 draft genome sequence for S. simiae and included it in comparative genomic analyses with 11 other Staphylococcus species including S. aureus. A genome based phylogeny of the genus confirms that S. simiae is the sister group to S. aureus and indicates that the most basal Staphylococcus lineage is Staphylococcus pseudintermedius, followed by Staphylococcus carnosus. Given the primary niche of these two latter taxa, compared to the other species in the genus, this phylogeny suggests that human adaptation evolved after the split of S. carnosus. The two coagulase-positive species (S. aureus and S. pseudintermedius) are not phylogenetically closest but share many virulence factors exclusively, suggesting that these genes were acquired by horizontal transfer. Enrichment in genes related to mobile elements such as prophage in S. aureus relative to S. simiae suggests that pathogenesis in the S. aureus group has developed by gene gain through horizontal transfer, after the split of S. aureus and S. simiae from their common ancestor. Conclusions Comparative genomic analyses across 12 Staphylococcus species provide hypotheses about lineages in which human adaptation has taken place and contributions of horizontal transfer in pathogenesis. PMID

  19. Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae

    Directory of Open Access Journals (Sweden)

    Suzuki Haruo

    2012-01-01

    Full Text Available Abstract Background Staphylococcus belongs to the Gram-positive low G + C content group of the Firmicutes division of bacteria. Staphylococcus aureus is an important human and veterinary pathogen that causes a broad spectrum of diseases, and has developed important multidrug resistant forms such as methicillin-resistant S. aureus (MRSA. Staphylococcus simiae was isolated from South American squirrel monkeys in 2000, and is a coagulase-negative bacterium, closely related, and possibly the sister group, to S. aureus. Comparative genomic analyses of closely related bacteria with different phenotypes can provide information relevant to understanding adaptation to host environment and mechanisms of pathogenicity. Results We determined a Roche/454 draft genome sequence for S. simiae and included it in comparative genomic analyses with 11 other Staphylococcus species including S. aureus. A genome based phylogeny of the genus confirms that S. simiae is the sister group to S. aureus and indicates that the most basal Staphylococcus lineage is Staphylococcus pseudintermedius, followed by Staphylococcus carnosus. Given the primary niche of these two latter taxa, compared to the other species in the genus, this phylogeny suggests that human adaptation evolved after the split of S. carnosus. The two coagulase-positive species (S. aureus and S. pseudintermedius are not phylogenetically closest but share many virulence factors exclusively, suggesting that these genes were acquired by horizontal transfer. Enrichment in genes related to mobile elements such as prophage in S. aureus relative to S. simiae suggests that pathogenesis in the S. aureus group has developed by gene gain through horizontal transfer, after the split of S. aureus and S. simiae from their common ancestor. Conclusions Comparative genomic analyses across 12 Staphylococcus species provide hypotheses about lineages in which human adaptation has taken place and contributions of horizontal

  20. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); R. Wojciechowski (Robert); Q. Fan (Qiao); J. Guggenheim (Jean); R. Höhn (René); S. MacGregor (Stuart); A.W. Hewit (Alex); A. Nag (Abhishek); C-Y. Cheng (Ching-Yu); E. Yonova-Doing (Ekaterina); X. Zhou (Xin); M.K. Ikram (Kamran); G.H.S. Buitendijk (Gabrielle); G. Mcmahon (George); J.P. Kemp (John); B.S. Pourcain (Beate); C.L. Simpson (Claire); M.J. Mäkelä; T. Lehtimäki (Terho); M. Kähönen (Mika); A.D. Paterson (Andrew); M. Hosseini (Mehran); H.S. Wong (Hoi Suen); L. Xu (Liang); J.B. Jonas; O. Pärssinen (Olavi); J. Wedenoja (Juho); S.P. Yip (Shea Ping); D.W.H. Ho (Daniel); C.P. Pang (Chi); L.J. Chen (Li); K.P. Burdon (Kathryn); J.E. Craig (Jamie); B.E.K. Klein (Barbara); B.E.K. Klein (Barbara); T. Haller (Toomas); A. Metspalu (Andres); C.C. Khor; E.S. Tai (Shyong); T. Aung (Tin); E.N. Vithana (Eranga); W.-T. Tay (Wan-Ting); V.A. Barathi (Veluchamy); P. Chen (Ping); R. Li (Rui); J. Liao (Jie); Y. Zheng (Yuhui); R.T.H. Ong (Rick Twee-Hee); A. Döring (Angela); D.M. Evans (David); N. Timpson (Nicholas); A. Verkerk; T. Meitinger (Thomas); O. Raitakari (Olli); F. Hawthorne (Felicia); T.D. Spector (Timothy); L.C. Karssen (Lennart); M. Pirastu (Mario); D. Murgia (Daniela); W.Q. Ang (Wei); A. Mishra (Aniket); G.W. Montgomery (Grant); C.E. Pennell (Craig); P. Cumberland (Phillippa); I. Cotlarciuc (Ioana); P. Mitchell (Paul); J.J. Wang (Jie Jin); M. Schache (Maria); S. Janmahasathian (Sarayut); R.P. Igo Jr. (Robert); J.H. Lass Jr. (Jonathan); E.Y. Chew (Emily); S.K. Iyengar (Sudha); T.G.M.F. Gorgels (Theo); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); Z. Vatavuk (Zoran); J.F. Wilson (James); B. Fleck (Brian); T. Zeller (Tanja); A. Mirshahi (Alireza); C. Müller (Christian); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); A. Hofman (Albert); B.A. Oostra (Ben); N. Amin (Najaf); A.A.B. Bergen (Arthur); Y.Y. Teo (Yik Ying); J.S. Rahi (Jugnoo); V. Vitart (Veronique); C. Williams (Cathy); P.N. Baird (Paul); T.Y. Wong (Tien); K. Oexle (Konrad); A.F.H. Pfeiffer (Andreas); D.A. Mackey (David); T.L. Young (Terri); C.M. van Duijn (Cock); S-M. Saw (Seang-Mei); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); C.C.W. Klaver (Caroline); C.J. Hammond (Christopher)

    2013-01-01

    textabstractRefractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European anc

  1. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); R. Wojciechowski (Robert); Q. Fan (Qiao); J. Guggenheim (Jean); R. Höhn (René); S. MacGregor (Stuart); A.W. Hewit (Alex); A. Nag (Abhishek); C-Y. Cheng (Ching-Yu); E. Yonova-Doing (Ekaterina); X. Zhou (Xin); M.K. Ikram (Kamran); G.H.S. Buitendijk (Gabrielle); G. Mcmahon (George); J.P. Kemp (John); B.S. Pourcain (Beate); C.L. Simpson (Claire); M.J. Mäkelä; T. Lehtimäki (Terho); M. Kähönen (Mika); A.D. Paterson (Andrew); M. Hosseini (Mehran); H.S. Wong (Hoi Suen); L. Xu (Liang); J.B. Jonas; O. Pärssinen (Olavi); J. Wedenoja (Juho); S.P. Yip (Shea Ping); D.W.H. Ho (Daniel); C.P. Pang (Chi); L.J. Chen (Li); K.P. Burdon (Kathryn); J.E. Craig (Jamie); B.E.K. Klein (Barbara); B.E.K. Klein (Barbara); T. Haller (Toomas); A. Metspalu (Andres); C.C. Khor; E.S. Tai (Shyong); T. Aung (Tin); E.N. Vithana (Eranga); W.-T. Tay (Wan-Ting); V.A. Barathi (Veluchamy); P. Chen (Ping); R. Li (Rui); J. Liao (Jie); Y. Zheng (Yuhui); R.T.H. Ong (Rick Twee-Hee); A. Döring (Angela); D.M. Evans (David); N.J. Timpson (Nicholas); A. Verkerk; T. Meitinger (Thomas); O. Raitakari (Olli); F. Hawthorne (Felicia); T.D. Spector (Timothy); L.C. Karssen (Lennart); M. Pirastu (Mario); D. Murgia (Daniela); W.Q. Ang (Wei); A. Mishra (Aniket); G.W. Montgomery (Grant); C.E. Pennell (Craig); P. Cumberland (Phillippa); I. Cotlarciuc (Ioana); P. Mitchell (Paul); J.J. Wang (Jie Jin); M. Schache (Maria); S. Janmahasathian (Sarayut); R.P. Igo Jr. (Robert); J.H. Lass Jr. (Jonathan); E.Y. Chew (Emily); S.K. Iyengar (Sudha); T.G.M.F. Gorgels (Theo); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); Z. Vatavuk (Zoran); J.F. Wilson (James); B. Fleck (Brian); T. Zeller (Tanja); A. Mirshahi (Alireza); C. Müller (Christian); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); A. Hofman (Albert); B.A. Oostra (Ben); N. Amin (Najaf); A.A.B. Bergen (Arthur); Y.Y. Teo (Yik Ying); J.S. Rahi (Jugnoo); V. Vitart (Veronique); C. Williams (Cathy); P.N. Baird (Paul); T.Y. Wong (Tien); K. Oexle (Konrad); A.F.H. Pfeiffer (Andreas); D.A. Mackey (David); T.L. Young (Terri); C.M. van Duijn (Cock); S-M. Saw (Seang-Mei); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); C.C.W. Klaver (Caroline); C.J. Hammond (Christopher)

    2013-01-01

    textabstractRefractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European

  2. Molecular Characterization of Five Potyviruses Infecting Korean Sweet Potatoes Based on Analyses of Complete Genome Sequences

    Directory of Open Access Journals (Sweden)

    Hae-Ryun Kwak

    2015-12-01

    Full Text Available Sweet potatoes (Ipomea batatas L. are grown extensively, in tropical and temperate regions, and are important food crops worldwide. In Korea, potyviruses, including Sweet potato feathery mottle virus (SPFMV, Sweet potato virus C (SPVC, Sweet potato virus G (SPVG, Sweet potato virus 2 (SPV2, and Sweet potato latent virus (SPLV, have been detected in sweet potato fields at a high (~95% incidence. In the present work, complete genome sequences of 18 isolates, representing the five potyviruses mentioned above, were compared with previously reported genome sequences. The complete genomes consisted of 10,081 to 10,830 nucleotides, excluding the poly-A tails. Their genomic organizations were typical of the Potyvirus genus, including one target open reading frame coding for a putative polyprotein. Based on phylogenetic analyses and sequence comparisons, the Korean SPFMV isolates belonged to the strains RC and O with >98% nucleotide sequence identity. Korean SPVC isolates had 99% identity to the Japanese isolate SPVC-Bungo and 70% identity to the SPFMV isolates. The Korean SPVG isolates showed 99% identity to the three previously reported SPVG isolates. Korean SPV2 isolates had 97% identity to the SPV2 GWB-2 isolate from the USA. Korean SPLV isolates had a relatively low (88% nucleotide sequence identity with the Taiwanese SPLV-TW isolates, and they were phylogenetically distantly related to SPFMV isolates. Recombination analysis revealed that possible recombination events occurred in the P1, HC-Pro and NIa-NIb regions of SPFMV and SPLV isolates and these regions were identified as hotspots for recombination in the sweet potato potyviruses.

  3. Diversity and genome dynamics of marine cyanophages using metagenomic analyses.

    Science.gov (United States)

    Ma, Yingfei; Allen, Lisa Zeigler; Palenik, Brian

    2014-12-01

    Cyanophages are abundant in the oceanic environment and directly impact cyanobacterial distributions, physiological processes and evolution. Two samples collected from coastal Maine in July and September 2009 were enriched for Synechococcus cells using flow cytometry and examined through metagenomic sequencing. Homology-based sequence prediction indicated cyanophages, largely myoviruses, accounted for almost half the reads and provided insights into environmental infection events. T4-phage core-gene phylogenetic reconstruction revealed unique diversity among uncultured cyanophages and reference isolates resulting in identification of a new phylogenetic cluster. Genomic comparison of reference cyanophage strains S-SM2 and Syn1 with putative homologous contigs recovered from metagenomes provided evidence that gene insertion, deletion and recombination have occurred among, and are likely important for diversification of, natural populations. Identification of putative genetic exchange between cyanophage and non-cyanophage viruses, i.e. Micromonas virus and Pelagibacter phage, supports hypotheses related to a significant role for viruses in mediating transfer of genetic material between taxonomically diverse organisms with overlapping ecological niches.

  4. Comparative Genomic and Transcriptional Analyses of CRISPR Systems Across the Genus Pyrobaculum

    Directory of Open Access Journals (Sweden)

    David L Bernick

    2012-07-01

    Full Text Available Within the domain Archaea, the CRISPR immune system appears to be nearly ubiquitous based on computational genome analyses. Initial studies in bacteria demonstrated that the CRISPR system targets invading plasmid and viral DNA. Recent experiments in the model archaeon Pyrococcus furiosus uncovered a novel RNA-targeting variant of the CRISPR system potentially unique to archaea. Because our understanding of CRISPR system evolution in other archaea is limited, we have taken a comparative genomic and transcriptomic view of the CRISPR arrays across six diverse species within the crenarchaeal genus Pyrobaculum. We present transcriptional data from each of four species in the genus (P. aerophilum, P. islandicum, P. calidifontis, P. arsenaticum, analyzing mature CRISPR-associated small RNA abundance from over 20 arrays. Within the genus, there is remarkable conservation of CRISPR array structure, as well as unique features that are have not been studied in other archaeal systems. These unique features include: a nearly invariant CRISPR promoter, conservation of direct repeat families, the 5' polarity of CRISPR-associated small RNA abundance, and a novel CRISPR-specific association with homologues of nurA and herA. These analyses provide a genus-level evolutionary perspective on archaeal CRISPR systems, broadening our understanding beyond existing non-comparative model systems.

  5. Whole-genome analyses of speciation events in pathogenic Brucellae

    Energy Technology Data Exchange (ETDEWEB)

    Chain, Patrick S. G. [Lawrence Livermore National Laboratory (LLNL); Comerci, Diego J. [Universidad Nacional de General San Martin; Tolmasky, Marcelo E. [California State University; Larimer, Frank W [ORNL; Malfatti, Stephanie [Lawrence Livermore National Laboratory (LLNL); Vergez, Lisa [Lawrence Livermore National Laboratory (LLNL); Aguero, Fernan [Universidad Nacional de General San Martin; Land, Miriam L [ORNL; Ugalde, Rodolfo A. [Universidad Nacional de General San Martin; Garcia, Emilio [Lawrence Livermore National Laboratory (LLNL)

    2005-12-01

    Despite their high DNA identity and a proposal to group classical Brucella species as biovars of Brucella melitensis, the commonly recognized Brucella species can be distinguished by distinct biochemical and fatty acid characters, as well as by a marked host range (e.g., Brucella suis for swine, B. melitensis for sheep and goats, and Brucella abortus for cattle). Here we present the genome of B. abortus 2308, the virulent prototype biovar 1 strain, and its comparison to the two other human pathogenic Brucella species and to B. abortus field isolate 9-941. The global distribution of pseudogenes, deletions, and insertions supports previous indications that B. abortus and B. melitensis share a common ancestor that diverged from B. suis. With the exception of a dozen genes, the genetic complements of both B. abortus strains are identical, whereas the three species differ in gene content and pseudogenes. The pattern of species-specific gene inactivations affecting transcriptional regulators and outer membrane proteins suggests that these inactivations may play an important role in the establishment of host specificity and may have been a primary driver of speciation in the genus Brucella. Despite being nonmotile, the brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures and may contribute to differences in host specificity and virulence. Metabolic changes such as the lack of complete metabolic pathways for the synthesis of numerous compounds (e.g., glycogen, biotin, NAD, and choline) are consistent with adaptation of brucellae to an intracellular life-style.

  6. Deciphering Clostridium tyrobutyricum Metabolism Based on the Whole-Genome Sequence and Proteome Analyses

    Directory of Open Access Journals (Sweden)

    Joungmin Lee

    2016-06-01

    Full Text Available Clostridium tyrobutyricum is a Gram-positive anaerobic bacterium that efficiently produces butyric acid and is considered a promising host for anaerobic production of bulk chemicals. Due to limited knowledge on the genetic and metabolic characteristics of this strain, however, little progress has been made in metabolic engineering of this strain. Here we report the complete genome sequence of C. tyrobutyricum KCTC 5387 (ATCC 25755, which consists of a 3.07-Mbp chromosome and a 63-kbp plasmid. The results of genomic analyses suggested that C. tyrobutyricum produces butyrate from butyryl-coenzyme A (butyryl-CoA through acetate reassimilation by CoA transferase, differently from Clostridium acetobutylicum, which uses the phosphotransbutyrylase-butyrate kinase pathway; this was validated by reverse transcription-PCR (RT-PCR of related genes, protein expression levels, in vitro CoA transferase assay, and fed-batch fermentation. In addition, the changes in protein expression levels during the course of batch fermentations on glucose were examined by shotgun proteomics. Unlike C. acetobutylicum, the expression levels of proteins involved in glycolytic and fermentative pathways in C. tyrobutyricum did not decrease even at the stationary phase. Proteins related to energy conservation mechanisms, including Rnf complex, NfnAB, and pyruvate-phosphate dikinase that are absent in C. acetobutylicum, were identified. Such features explain why this organism can produce butyric acid to a much higher titer and better tolerate toxic metabolites. This study presenting the complete genome sequence, global protein expression profiles, and genome-based metabolic characteristics during the batch fermentation of C. tyrobutyricum will be valuable in designing strategies for metabolic engineering of this strain.

  7. Genomic analyses with biofilter 2.0: knowledge driven filtering, annotation, and model development.

    Science.gov (United States)

    Pendergrass, Sarah A; Frase, Alex; Wallace, John; Wolfe, Daniel; Katiyar, Neerja; Moore, Carrie; Ritchie, Marylyn D

    2013-12-30

    The ever-growing wealth of biological information available through multiple comprehensive database repositories can be leveraged for advanced analysis of data. We have now extensively revised and updated the multi-purpose software tool Biofilter that allows researchers to annotate and/or filter data as well as generate gene-gene interaction models based on existing biological knowledge. Biofilter now has the Library of Knowledge Integration (LOKI), for accessing and integrating existing comprehensive database information, including more flexibility for how ambiguity of gene identifiers are handled. We have also updated the way importance scores for interaction models are generated. In addition, Biofilter 2.0 now works with a range of types and formats of data, including single nucleotide polymorphism (SNP) identifiers, rare variant identifiers, base pair positions, gene symbols, genetic regions, and copy number variant (CNV) location information. Biofilter provides a convenient single interface for accessing multiple publicly available human genetic data sources that have been compiled in the supporting database of LOKI. Information within LOKI includes genomic locations of SNPs and genes, as well as known relationships among genes and proteins such as interaction pairs, pathways and ontological categories.Via Biofilter 2.0 researchers can:• Annotate genomic location or region based data, such as results from association studies, or CNV analyses, with relevant biological knowledge for deeper interpretation• Filter genomic location or region based data on biological criteria, such as filtering a series SNPs to retain only SNPs present in specific genes within specific pathways of interest• Generate Predictive Models for gene-gene, SNP-SNP, or CNV-CNV interactions based on biological information, with priority for models to be tested based on biological relevance, thus narrowing the search space and reducing multiple hypothesis-testing. Biofilter is a software

  8. Genome-based comparative analyses of Antarctic and temperate species of Paenibacillus.

    Directory of Open Access Journals (Sweden)

    Melissa Dsouza

    Full Text Available Antarctic soils represent a unique environment characterised by extremes of temperature, salinity, elevated UV radiation, low nutrient and low water content. Despite the harshness of this environment, members of 15 bacterial phyla have been identified in soils of the Ross Sea Region (RSR. However, the survival mechanisms and ecological roles of these phyla are largely unknown. The aim of this study was to investigate whether strains of Paenibacillus darwinianus owe their resilience to substantial genomic changes. For this, genome-based comparative analyses were performed on three P. darwinianus strains, isolated from gamma-irradiated RSR soils, together with nine temperate, soil-dwelling Paenibacillus spp. The genome of each strain was sequenced to over 1,000-fold coverage, then assembled into contigs totalling approximately 3 Mbp per genome. Based on the occurrence of essential, single-copy genes, genome completeness was estimated at approximately 88%. Genome analysis revealed between 3,043-3,091 protein-coding sequences (CDSs, primarily associated with two-component systems, sigma factors, transporters, sporulation and genes induced by cold-shock, oxidative and osmotic stresses. These comparative analyses provide an insight into the metabolic potential of P. darwinianus, revealing potential adaptive mechanisms for survival in Antarctic soils. However, a large proportion of these mechanisms were also identified in temperate Paenibacillus spp., suggesting that these mechanisms are beneficial for growth and survival in a range of soil environments. These analyses have also revealed that the P. darwinianus genomes contain significantly fewer CDSs and have a lower paralogous content. Notwithstanding the incompleteness of the assemblies, the large differences in genome sizes, determined by the number of genes in paralogous clusters and the CDS content, are indicative of genome content scaling. Finally, these sequences are a resource for further

  9. Deciphering the cryptic genome: genome-wide analyses of the rice pathogen Fusarium fujikuroi reveal complex regulation of secondary metabolism and novel metabolites.

    Directory of Open Access Journals (Sweden)

    Philipp Wiemann

    Full Text Available The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs, but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19 and another that includes a non-ribosomal peptide synthetase gene (NRPS31 are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary

  10. Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

    Science.gov (United States)

    Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

    2013-01-01

    The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

  11. Sterol and genomic analyses validate the sponge biomarker hypothesis.

    Science.gov (United States)

    Gold, David A; Grabenstatter, Jonathan; de Mendoza, Alex; Riesgo, Ana; Ruiz-Trillo, Iñaki; Summons, Roger E

    2016-03-01

    Molecular fossils (or biomarkers) are key to unraveling the deep history of eukaryotes, especially in the absence of traditional fossils. In this regard, the sterane 24-isopropylcholestane has been proposed as a molecular fossil for sponges, and could represent the oldest evidence for animal life. The sterane is found in rocks ∼650-540 million y old, and its sterol precursor (24-isopropylcholesterol, or 24-ipc) is synthesized today by certain sea sponges. However, 24-ipc is also produced in trace amounts by distantly related pelagophyte algae, whereas only a few close relatives of sponges have been assayed for sterols. In this study, we analyzed the sterol and gene repertoires of four taxa (Salpingoeca rosetta, Capsaspora owczarzaki, Sphaeroforma arctica, and Creolimax fragrantissima), which collectively represent the major living animal outgroups. We discovered that all four taxa lack C30 sterols, including 24-ipc. By building phylogenetic trees for key enzymes in 24-ipc biosynthesis, we identified a candidate gene (carbon-24/28 sterol methyltransferase, or SMT) responsible for 24-ipc production. Our results suggest that pelagophytes and sponges independently evolved C30 sterol biosynthesis through clade-specific SMT duplications. Using a molecular clock approach, we demonstrate that the relevant sponge SMT duplication event overlapped with the appearance of 24-isopropylcholestanes in the Neoproterozoic, but that the algal SMT duplication event occurred later in the Phanerozoic. Subsequently, pelagophyte algae and their relatives are an unlikely alternative to sponges as a source of Neoproterozoic 24-isopropylcholestanes, consistent with growing evidence that sponges evolved long before the Cambrian explosion ∼542 million y ago.

  12. Genomic analyses confirm close relatedness between Rhodococcus defluvii and Rhodococcus equi (Rhodococcus hoagii)

    OpenAIRE

    Sangal, Vartul; Jones, Amanda; GOODFELLOW, Michael; Hoskisson, Paul; Kämpfer, Peter; Sutcliffe, Iain

    2015-01-01

    Rhodococcus defluvii strain Ca11T was isolated from a bioreactor involved in extensive phosphorus removal. We have sequenced the whole genome of this strain and our comparative genomic and phylogenetic analyses confirm its close relatedness with Rhodococcus equi (Rhodococcus hoagii) strains, which share >80% of the gene content. The R. equi virulence plasmid is absent though most of the chromosomal R. equi virulence-associated genes are present in R. defluvii Ca11T. These data suggest that al...

  13. In silico phylogenetic and virulence gene profile analyses of avian pathogenic Escherichia coli genome sequences

    Directory of Open Access Journals (Sweden)

    Thaís C.G. Rojas

    2014-02-01

    Full Text Available Avian pathogenic Escherichia coli (APEC infections are responsible for significant losses in the poultry industry worldwide. A zoonotic risk has been attributed to APEC strains because they present similarities to extraintestinal pathogenic E. coli (ExPEC associated with illness in humans, mainly urinary tract infections and neonatal meningitis. Here, we present in silico analyses with pathogenic E. coli genome sequences, including recently available APEC genomes. The phylogenetic tree, based on multi-locus sequence typing (MLST of seven housekeeping genes, revealed high diversity in the allelic composition. Nevertheless, despite this diversity, the phylogenetic tree was able to cluster the different pathotypes together. An in silico virulence gene profile was also determined for each of these strains, through the presence or absence of 83 well-known virulence genes/traits described in pathogenic E. coli strains. The MLST phylogeny and the virulence gene profiles demonstrated a certain genetic similarity between Brazilian APEC strains, APEC isolated in the United States, UPEC (uropathogenic E. coli and diarrheagenic strains isolated from humans. This correlation corroborates and reinforces the zoonotic potential hypothesis proposed to APEC.

  14. Extending pathways and processes using molecular interaction networks to analyse cancer genome data

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    Krasnogor Natalio

    2010-12-01

    Full Text Available Abstract Background Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways. Results We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes. Conclusions The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.

  15. DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs.

    Science.gov (United States)

    Ogata, Jun; Uchiyama, Nahoko; Kikura-Hanajiri, Ruri; Goda, Yukihiro

    2013-04-10

    In recent years, various herbal products adulterated with synthetic cannabinoids have been distributed worldwide via the Internet. These herbal products are mostly sold as incense, and advertised as not for human consumption. Although their labels indicate that they contain mixtures of several potentially psychoactive plants, and numerous studies have reported that they contain a variety of synthetic cannabinoids, their exact botanical contents are not always clear. In this study, we investigated the origins of botanical materials in 62 Spice-like herbal products distributed on the illegal drug market in Japan, by DNA sequence analyses and BLAST searches. The nucleotide sequences of four regions were analyzed to identify the origins of each plant species in the herbal mixtures. The sequences of "Damiana" (Turnera diffusa) and Lamiaceae herbs (Mellissa, Mentha and Thymus) were frequently detected in a number of products. However, the sequences of other plant species indicated on the packaging labels were not detected. In a few products, DNA fragments of potent psychotropic plants were found, including marijuana (Cannabis sativa), "Diviner's Sage" (Salvia divinorum) and "Kratom" (Mitragyna speciosa). Their active constituents were also confirmed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), although these plant names were never indicated on the labels. Most plant species identified in the products were different from the plants indicated on the labels. The plant materials would be used mainly as diluents for the psychoactive synthetic compounds, because no reliable psychoactive effects have been reported for most of the identified plants, with the exception of the psychotropic plants named above.

  16. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits

    Science.gov (United States)

    Castillo, Daniel; Alvise, Paul D.; Xu, Ruiqi; Zhang, Faxing; Middelboe, Mathias

    2017-01-01

    ABSTRACT Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood. Here, we analyzed whole-genome sequences of a collection of V. anguillarum strains and compared them to virulence of the strains as determined in larval challenge assays. Previously identified virulence factors were globally distributed among the strains, with some genetic diversity. However, the pan-genome revealed that six out of nine high-virulence strains possessed a unique accessory genome that was attributed to pathogenic genomic islands, prophage-like elements, virulence factors, and a new set of gene clusters involved in biosynthesis, modification, and transport of polysaccharides. In contrast, V. anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest a link between genotype and virulence characteristics of Vibrio anguillarum, which can be used to unravel the molecular evolution of V. anguillarum and can also be important from survey and diagnostic perspectives. IMPORTANCE Comparative genome analysis of strains of a pathogenic bacterial species can be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast, V. anguillarum strains that were medium to nonvirulent had low genomic diversity. Integration of genomic and phenotypic features provides

  17. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits.

    Science.gov (United States)

    Castillo, Daniel; Alvise, Paul D; Xu, Ruiqi; Zhang, Faxing; Middelboe, Mathias; Gram, Lone

    2017-01-01

    Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood. Here, we analyzed whole-genome sequences of a collection of V. anguillarum strains and compared them to virulence of the strains as determined in larval challenge assays. Previously identified virulence factors were globally distributed among the strains, with some genetic diversity. However, the pan-genome revealed that six out of nine high-virulence strains possessed a unique accessory genome that was attributed to pathogenic genomic islands, prophage-like elements, virulence factors, and a new set of gene clusters involved in biosynthesis, modification, and transport of polysaccharides. In contrast, V. anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest a link between genotype and virulence characteristics of Vibrio anguillarum, which can be used to unravel the molecular evolution of V. anguillarum and can also be important from survey and diagnostic perspectives. IMPORTANCE Comparative genome analysis of strains of a pathogenic bacterial species can be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast, V. anguillarum strains that were medium to nonvirulent had low genomic diversity. Integration of genomic and phenotypic features provides insights

  18. Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions.

    Directory of Open Access Journals (Sweden)

    Mohamed B F Hawash

    Full Text Available The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates.We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related.Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates.

  19. Genomics and Comparative Genomic Analyses Provide Insight into the Taxonomy and Pathogenic Potential of Novel Emmonsia Pathogens

    Science.gov (United States)

    Yang, Ying; Ye, Qiang; Li, Kang; Li, Zongwei; Bo, Xiaochen; Li, Zhen; Xu, Yingchun; Wang, Shengqi; Wang, Peng; Chen, Huipeng; Wang, Junzhi

    2017-01-01

    Over the last 50 years, newly described species of Emmonsia-like fungi have been implicated globally as sources of systemic human mycosis (emmonsiosis). Their ability to convert into yeast-like cells capable of replication and extra-pulmonary dissemination during the course of infection differentiates them from classical Emmonsia species. Immunocompromised patients are at highest risk of emmonsiosis and exhibit high mortality rates. In order to investigate the molecular basis for pathogenicity of the newly described Emmonsia species, genomic sequencing and comparative genomic analyses of Emmonsia sp. 5z489, which was isolated from a non-deliberately immunosuppressed diabetic patient in China and represents a novel seventh isolate of Emmonsia-like fungi, was performed. The genome size of 5z489 was 35.5 Mbp in length, which is ~5 Mbp larger than other Emmonsia strains. Further, 9,188 protein genes were predicted in the 5z489 genome and 16% of the assembly was identified as repetitive elements, which is the largest abundance in Emmonsia species. Phylogenetic analyses based on whole genome data classified 5z489 and CAC-2015a, another novel isolate, as members of the genus Emmonsia. Our analyses showed that divergences among Emmonsia occurred much earlier than other genera within the family Ajellomycetaceae, suggesting relatively distant evolutionary relationships among the genus. Through comparisons of Emmonsia species, we discovered significant pathogenicity characteristics within the genus as well as putative virulence factors that may play a role in the infection and pathogenicity of the novel Emmonsia strains. Moreover, our analyses revealed a novel distribution mode of DNA methylation patterns across the genome of 5z489, with >50% of methylated bases located in intergenic regions. These methylation patterns differ considerably from other reported fungi, where most methylation occurs in repetitive loci. It is unclear if this difference is related to physiological

  20. DCJ path formulation for genome transformations which include insertions, deletions, and duplications.

    Science.gov (United States)

    Yancopoulos, Sophia; Friedberg, Richard

    2009-10-01

    We extend the double cut and join operation (DCJ) paradigm to perform genome rearrangements on pairs of genomes having unequal gene content and/or multiple copies by permitting genes in one genome which are completely or partially unmatched in the other. The existence of unmatched gene ends introduces new kinds of paths in the adjacency graph, since some paths can now terminate internal to a chromosome and not on telomeres. We introduce "ghost adjacencies" to supply the missing gene ends in the genome not containing them. Ghosts enable us to close paths that were due to incomplete matching, just as null points enable us to close even paths terminating in telomeres. We define generalized DCJ operations on the generalized adjacency graph, and give a prescription for calculating the DCJ distance for the expanded repertoire of operations, which includes insertions, deletions, and duplications. For the case of insertions and deletions, with linear as well as circular chromosomes, we suggest permitting a "nugh" (half ghost, half null), which can shorten the distance. We give algorithms for the optimal closure, with and without nughs, and give the resulting distance formula in terms of paths. For certain simplest cases, we calculate the number of optimal ways to close the graph.

  1. Bootstrap, Bayesian probability and maximum likelihood mapping: exploring new tools for comparative genome analyses

    Directory of Open Access Journals (Sweden)

    Gogarten J Peter

    2002-02-01

    Full Text Available Abstract Background Horizontal gene transfer (HGT played an important role in shaping microbial genomes. In addition to genes under sporadic selection, HGT also affects housekeeping genes and those involved in information processing, even ribosomal RNA encoding genes. Here we describe tools that provide an assessment and graphic illustration of the mosaic nature of microbial genomes. Results We adapted the Maximum Likelihood (ML mapping to the analyses of all detected quartets of orthologous genes found in four genomes. We have automated the assembly and analyses of these quartets of orthologs given the selection of four genomes. We compared the ML-mapping approach to more rigorous Bayesian probability and Bootstrap mapping techniques. The latter two approaches appear to be more conservative than the ML-mapping approach, but qualitatively all three approaches give equivalent results. All three tools were tested on mitochondrial genomes, which presumably were inherited as a single linkage group. Conclusions In some instances of interphylum relationships we find nearly equal numbers of quartets strongly supporting the three possible topologies. In contrast, our analyses of genome quartets containing the cyanobacterium Synechocystis sp. indicate that a large part of the cyanobacterial genome is related to that of low GC Gram positives. Other groups that had been suggested as sister groups to the cyanobacteria contain many fewer genes that group with the Synechocystis orthologs. Interdomain comparisons of genome quartets containing the archaeon Halobacterium sp. revealed that Halobacterium sp. shares more genes with Bacteria that live in the same environment than with Bacteria that are more closely related based on rRNA phylogeny . Many of these genes encode proteins involved in substrate transport and metabolism and in information storage and processing. The performed analyses demonstrate that relationships among prokaryotes cannot be accurately

  2. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits

    DEFF Research Database (Denmark)

    Castillo, Daniel; D'Alvise, Paul; Xu, Ruiqi

    2017-01-01

    Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood....... anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest...... be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast...

  3. Whole-genome analyses of Korean native and Holstein cattle breeds by massively parallel sequencing.

    Directory of Open Access Journals (Sweden)

    Jung-Woo Choi

    Full Text Available A main goal of cattle genomics is to identify DNA differences that account for variations in economically important traits. In this study, we performed whole-genome analyses of three important cattle breeds in Korea--Hanwoo, Jeju Heugu, and Korean Holstein--using the Illumina HiSeq 2000 sequencing platform. We achieved 25.5-, 29.6-, and 29.5-fold coverage of the Hanwoo, Jeju Heugu, and Korean Holstein genomes, respectively, and identified a total of 10.4 million single nucleotide polymorphisms (SNPs, of which 54.12% were found to be novel. We also detected 1,063,267 insertions-deletions (InDels across the genomes (78.92% novel. Annotations of the datasets identified a total of 31,503 nonsynonymous SNPs and 859 frameshift InDels that could affect phenotypic variations in traits of interest. Furthermore, genome-wide copy number variation regions (CNVRs were detected by comparing the Hanwoo, Jeju Heugu, and previously published Chikso genomes against that of Korean Holstein. A total of 992, 284, and 1881 CNVRs, respectively, were detected throughout the genome. Moreover, 53, 65, 45, and 82 putative regions of homozygosity (ROH were identified in Hanwoo, Jeju Heugu, Chikso, and Korean Holstein respectively. The results of this study provide a valuable foundation for further investigations to dissect the molecular mechanisms underlying variation in economically important traits in cattle and to develop genetic markers for use in cattle breeding.

  4. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Simon, Ronald; Feuerbach, Lars;

    2013-01-01

    comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS......Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued...... gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity...

  5. Comparative genomic and morphological analyses of Listeria phages isolated from farm environments.

    Science.gov (United States)

    Denes, Thomas; Vongkamjan, Kitiya; Ackermann, Hans-Wolfgang; Moreno Switt, Andrea I; Wiedmann, Martin; den Bakker, Henk C

    2014-08-01

    The genus Listeria is ubiquitous in the environment and includes the globally important food-borne pathogen Listeria monocytogenes. While the genomic diversity of Listeria has been well studied, considerably less is known about the genomic and morphological diversity of Listeria bacteriophages. In this study, we sequenced and analyzed the genomes of 14 Listeria phages isolated mostly from New York dairy farm environments as well as one related Enterococcus faecalis phage to obtain information on genome characteristics and diversity. We also examined 12 of the phages by electron microscopy to characterize their morphology. These Listeria phages, based on gene orthology and morphology, together with previously sequenced Listeria phages could be classified into five orthoclusters, including one novel orthocluster. One orthocluster (orthocluster I) consists of large genome (~135-kb) myoviruses belonging to the genus “Twort-like viruses,” three orthoclusters (orthoclusters II to IV) contain small-genome (36- to 43-kb) siphoviruses with icosahedral heads, and the novel orthocluster V contains medium-sized-genome (~66-kb) siphoviruses with elongated heads. A novel orthocluster (orthocluster VI) of E. faecalis phages, with medium-sized genomes (~56 kb), was identified, which grouped together and shares morphological features with the novel Listeria phage orthocluster V. This new group of phages (i.e., orthoclusters V and VI) is composed of putative lytic phages that may prove to be useful in phage-based applications for biocontrol, detection, and therapeutic purposes.

  6. RSIADB, a collective resource for genome and transcriptome analyses in Rhizoctonia solani AG1 IA.

    Science.gov (United States)

    Chen, Lei; Ai, Peng; Zhang, Jinfeng; Deng, Qiming; Wang, Shiquan; Li, Shuangcheng; Zhu, Jun; Li, Ping; Zheng, Aiping

    2016-01-01

    Rice [Oryza sativa (L.)] feeds more than half of the world's population. Rhizoctonia solaniis a major fungal pathogen of rice causing extreme crop losses in all rice-growing regions of the world. R. solani AG1 IA is a major cause of sheath blight in rice. In this study, we constructed a comprehensive and user-friendly web-based database, RSIADB, to analyse its draft genome and transcriptome. The database was built using the genome sequence (10,489 genes) and annotation information for R. solani AG1 IA. A total of six RNAseq samples of R. solani AG1 IA were also analysed, corresponding to 10, 18, 24, 32, 48 and 72 h after infection of rice leaves. The RSIADB database enables users to search, browse, and download gene sequences for R. solani AG1 IA, and mine the data using BLAST, Sequence Extractor, Browse and Construction Diagram tools that were integrated into the database. RSIADB is an important genomic resource for scientists working with R. solani AG1 IA and will assist researchers in analysing the annotated genome and transcriptome of this pathogen. This resource will facilitate studies on gene function, pathogenesis factors and secreted proteins, as well as provide an avenue for comparative analyses of genes expressed during different stages of infection. Database URL:http://genedenovoweb.ticp.net:81/rsia/index.php.

  7. Comparative transcriptome analyses and genome assembly of Fusarium oxysporum f. sp. cubense

    NARCIS (Netherlands)

    Dita, M.A.; Herai, R.; Waalwijk, C.; Yamagishi, M.; Giachetto, P.; Ferreira, G.; Souza, de M.; Kema, G.H.J.

    2013-01-01

    Fusarium oxysporum f. sp. cubense (Foc), the causal agent of Fusarium wilt of banana, is a highly destructive and genetically diverse pathogen. Despite its economic importance, genomic information about Foc is limited and no transcriptomic analyses have been reported so far. By using 454 sequencing

  8. Genome-wide meta-analyses identify multiple loci associated with smoking behavior

    NARCIS (Netherlands)

    H. Furberg (Helena); Y. Kim (Yunjung); J. Dackor (Jennifer); E.A. Boerwinkle (Eric); N. Franceschini (Nora); D. Ardissino (Diego); L. Bernardinelli (Luisa); P.M. Mannucci (Pier); F. Mauri (Francesco); P.A. Merlini (Piera); D. Absher (Devin); T.L. Assimes (Themistocles); S.P. Fortmann (Stephen); C. Iribarren (Carlos); J.W. Knowles (Joshua); T. Quertermous (Thomas); L. Ferrucci (Luigi); T. Tanaka (Toshiko); J.C. Bis (Joshua); T. Haritunians (Talin); B. McKnight (Barbara); B.M. Psaty (Bruce); K.D. Taylor (Kent); E.L. Thacker (Evan); P. Almgren (Peter); L. Groop (Leif); C. Ladenvall (Claes); M. Boehnke (Michael); A.U. Jackson (Anne); K.L. Mohlke (Karen); H.M. Stringham (Heather); J. Tuomilehto (Jaakko); E.J. Benjamin (Emelia); S.J. Hwang; D. Levy (Daniel); S.R. Preis; R.S. Vasan (Ramachandran Srini); J. Duan (Jubao); P.V. Gejman (Pablo); D.F. Levinson (Douglas); A.R. Sanders (Alan); J. Shi (Jianxin); E.H. Lips (Esther); J.D. McKay (James); A. Agudo (Antonio); L. Barzan (Luigi); V. Bencko (Vladimir); S. Benhamou (Simone); X. Castellsagué (Xavier); C. Canova (Cristina); D.I. Conway (David); E. Fabianova (Eleonora); L. Foretova (Lenka); V. Janout (Vladimir); C.M. Healy (Claire); I. Holcátová (Ivana); K. Kjaerheim (Kristina); P. Lagiou; J. Lissowska (Jolanta); R. Lowry (Ray); T.V. MacFarlane (Tatiana); D. Mates (Dana); L. Richiardi (Lorenzo); P. Rudnai (Peter); N. Szeszenia-Dabrowska (Neonilia); D. Zaridze; A. Znaor (Ariana); M. Lathrop (Mark); P. Brennan (Paul); S. Bandinelli (Stefania); T.M. Frayling (Timothy); J.M. Guralnik (Jack); Y. Milaneschi (Yuri); J.R.B. Perry (John); D. Altshuler (David); R. Elosua (Roberto); S. Kathiresan (Sekar); G. Lucas (Gavin); O. Melander (Olle); V. Salomaa (Veikko); S.M. Schwartz (Stephen); B.F. Voight (Benjamin); B.W.J.H. Penninx (Brenda); J.H. Smit (Johannes); N. Vogelzangs (Nicole); D.I. Boomsma (Dorret); E.J.C. de Geus (Eco); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); S.J. Chanock (Stephen); F. Gu (Fangyi); S.E. Hankinson (Susan); D. Hunter (David); A. Hofman (Albert); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); S. Walter (Stefan); D.I. Chasman (Daniel); B.M. Everett (Brendan); G. Pare (Guillaume); P.M. Ridker (Paul); M.D. Li (Ming); H.H. Maes (Hermine); J. Audrain-Mcgovern (Janet); D. Posthuma (Danielle); L.M. Thornton (Laura); C. Lerman (Caryn); J. Kaprio (Jaakko); J.E. Rose (Jed); J.P.A. Ioannidis (John); P. Kraft (Peter); D.Y. Lin (Dan); P.F. Sullivan (Patrick); C.J. O'Donnell (Christopher)

    2010-01-01

    textabstractConsistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (

  9. The complete mitochondrial genomes of four cockroaches (Insecta: Blattodea) and phylogenetic analyses within cockroaches.

    Science.gov (United States)

    Cheng, Xue-Fang; Zhang, Le-Ping; Yu, Dan-Na; Storey, Kenneth B; Zhang, Jia-Yong

    2016-07-15

    Three complete mitochondrial genomes of Blaberidae (Insecta: Blattodea) (Gromphadorhina portentosa, Panchlora nivea, Blaptica dubia) and one complete mt genome of Blattidae (Insecta: Blattodea) (Shelfordella lateralis) were sequenced to further understand the characteristics of cockroach mitogenomes and reconstruct the phylogenetic relationship of Blattodea. The gene order and orientation of these four cockroach genomes were similar to known cockroach mt genomes, and contained 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. The mt genomes of Blattodea exhibited a characteristics of a high A+T composition (70.7%-74.3%) and dominant usage of the TAA stop codon. The AT content of the whole mt genome, PCGs and total tRNAs in G. portentosa was the lowest in known cockroaches. The presence of a 71-bp intergenic spacer region between trnQ and trnM was a unique feature in B. dubia, but absent in other cockroaches, which can be explained by the duplication/random loss model. Based on the nucleotide and amino acid datasets of the 13 PCGs genes, neighbor-joining (NJ), maximum parsimony (MP), maximum likelihood (ML) and bayesian inference (BI) analyses were used to rebuild the phylogenetic relationship of cockroaches. All phylogenetic analyses consistently placed Isoptera as the sister cluster to Cryptocercidae of Blattodea. Ectobiidae and Blaberidae (Blaberoidea) formed a sister clade to Blattidae. Corydiidae is a sister clade of all the remaining cockroach species with a high value in NJ and MP analyses of nucleotide and amino acid datasets, and ML and BI analyses of the amino acid dataset.

  10. Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube.

    Science.gov (United States)

    Eckert, Mark A; Pan, Shawn; Hernandez, Kyle M; Loth, Rachel M; Andrade, Jorge; Volchenboum, Samuel L; Faber, Pieter; Montag, Anthony; Lastra, Ricardo; Peter, Marcus E; Yamada, S Diane; Lengyel, Ernst

    2016-12-01

    Accumulating evidence has supported the fallopian tube rather than the ovary as the origin for high-grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole-exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy-number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC. Phylogenetic analyses supported STIC as precursor lesions in half of our patient cohort, but also identified STIC as metastases in 2 patients. Ex vivo assays revealed that HGSOC spheroids can implant in the fallopian tube epithelium and mimic STIC lesions. That STIC may represent metastases calls into question the assumption that STIC are always indicative of primary fallopian tube cancers. We find that the putative precursor lesions for HGSOC, STIC, possess most of the genomic aberrations present in advanced cancers. In addition, a proportion of STIC represent intraepithelial metastases to the fallopian tube rather than the origin of HGSOC. Cancer Discov; 6(12); 1342-51. ©2016 AACR.See related commentary by Swisher et al., p. 1309This article is highlighted in the In This Issue feature, p. 1293. ©2016 American Association for Cancer Research.

  11. Genomic analyses confirm close relatedness between Rhodococcus defluvii and Rhodococcus equi (Rhodococcus hoagii).

    Science.gov (United States)

    Sangal, Vartul; Jones, Amanda L; Goodfellow, Michael; Hoskisson, Paul A; Kämpfer, Peter; Sutcliffe, Iain C

    2015-01-01

    Rhodococcus defluvii strain Ca11(T) was isolated from a bioreactor involved in extensive phosphorus removal. We have sequenced the whole genome of this strain, and our comparative genomic and phylogenetic analyses confirm its close relatedness with Rhodococcus equi (Rhodococcus hoagii) strains, which share >80 % of the gene content. The R. equi virulence plasmid is absent though most of the chromosomal R. equi virulence-associated genes are present in R. defluvii Ca11(T). These data suggest that although R. defluvii is an environmental organism, it has the potential to colonize animal hosts.

  12. Genetic Basis for Spontaneous Hybrid Genome Doubling during Allopolyploid Speciation of Common Wheat Shown by Natural Variation Analyses of the Paternal Species

    Science.gov (United States)

    Matsuoka, Yoshihiro; Nasuda, Shuhei; Ashida, Yasuyo; Nitta, Miyuki; Tsujimoto, Hisashi; Takumi, Shigeo; Kawahara, Taihachi

    2013-01-01

    The complex process of allopolyploid speciation includes various mechanisms ranging from species crosses and hybrid genome doubling to genome alterations and the establishment of new allopolyploids as persisting natural entities. Currently, little is known about the genetic mechanisms that underlie hybrid genome doubling, despite the fact that natural allopolyploid formation is highly dependent on this phenomenon. We examined the genetic basis for the spontaneous genome doubling of triploid F1 hybrids between the direct ancestors of allohexaploid common wheat (Triticum aestivum L., AABBDD genome), namely Triticumturgidum L. (AABB genome) and Aegilopstauschii Coss. (DD genome). An Ae. tauschii intraspecific lineage that is closely related to the D genome of common wheat was identified by population-based analysis. Two representative accessions, one that produces a high-genome-doubling-frequency hybrid when crossed with a T. turgidum cultivar and the other that produces a low-genome-doubling-frequency hybrid with the same cultivar, were chosen from that lineage for further analyses. A series of investigations including fertility analysis, immunostaining, and quantitative trait locus (QTL) analysis showed that (1) production of functional unreduced gametes through nonreductional meiosis is an early step key to successful hybrid genome doubling, (2) first division restitution is one of the cytological mechanisms that cause meiotic nonreduction during the production of functional male unreduced gametes, and (3) six QTLs in the Ae. tauschii genome, most of which likely regulate nonreductional meiosis and its subsequent gamete production processes, are involved in hybrid genome doubling. Interlineage comparisons of Ae. tauschii’s ability to cause hybrid genome doubling suggested an evolutionary model for the natural variation pattern of the trait in which non-deleterious mutations in six QTLs may have important roles. The findings of this study demonstrated that the

  13. Genetic basis for spontaneous hybrid genome doubling during allopolyploid speciation of common wheat shown by natural variation analyses of the paternal species.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Matsuoka

    Full Text Available The complex process of allopolyploid speciation includes various mechanisms ranging from species crosses and hybrid genome doubling to genome alterations and the establishment of new allopolyploids as persisting natural entities. Currently, little is known about the genetic mechanisms that underlie hybrid genome doubling, despite the fact that natural allopolyploid formation is highly dependent on this phenomenon. We examined the genetic basis for the spontaneous genome doubling of triploid F1 hybrids between the direct ancestors of allohexaploid common wheat (Triticum aestivum L., AABBDD genome, namely Triticumturgidum L. (AABB genome and Aegilopstauschii Coss. (DD genome. An Ae. tauschii intraspecific lineage that is closely related to the D genome of common wheat was identified by population-based analysis. Two representative accessions, one that produces a high-genome-doubling-frequency hybrid when crossed with a T. turgidum cultivar and the other that produces a low-genome-doubling-frequency hybrid with the same cultivar, were chosen from that lineage for further analyses. A series of investigations including fertility analysis, immunostaining, and quantitative trait locus (QTL analysis showed that (1 production of functional unreduced gametes through nonreductional meiosis is an early step key to successful hybrid genome doubling, (2 first division restitution is one of the cytological mechanisms that cause meiotic nonreduction during the production of functional male unreduced gametes, and (3 six QTLs in the Ae. tauschii genome, most of which likely regulate nonreductional meiosis and its subsequent gamete production processes, are involved in hybrid genome doubling. Interlineage comparisons of Ae. tauschii's ability to cause hybrid genome doubling suggested an evolutionary model for the natural variation pattern of the trait in which non-deleterious mutations in six QTLs may have important roles. The findings of this study demonstrated

  14. Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease

    Energy Technology Data Exchange (ETDEWEB)

    Hugot, J.P.; Laurent-Puig, P.; Gower-Rousseau, C.; Caillat-Zueman, S.; Beaugerie, L.; Dupas, J.L.; Van Gossum, A.; Bonaiti-Pellie, C.; Cortot, A.

    1994-08-15

    Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lod score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than -2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. 37 refs., 2 figs., 2 tabs.

  15. From reptilian phylogenomics to reptilian genomes: analyses of c-Jun and DJ-1 proto-oncogenes.

    Science.gov (United States)

    Katsu, Y; Braun, E L; Guillette, L J; Iguchi, T

    2009-01-01

    Genome projects have revolutionized our understanding of both molecular biology and evolution, but there has been a limited collection of genomic data from reptiles. This is surprising given the pivotal position of reptiles in vertebrate phylogeny and the potential utility of information from reptiles for understanding a number of biological phenomena, such as sex determination. Although there are many potential uses for genomic data, one important and useful approach is phylogenomics. Here we report cDNA sequences for the c-Jun(JUN) and DJ-1(PARK7) proto-oncogenes from 3 reptiles (the American alligator, Nile crocodile, and Florida red-belly turtle), show that both genes are expressed in the alligator, and integrate them into analyses of their homologs from other organisms. With these taxa it was possible to conduct analyses that include all major vertebrate lineages. Analyses of c-Jun revealed an unexpected but well-supported frog-turtle clade while analyses of DJ-1 revealed a topology largely congruent with expectation based upon other data. The conflict between the c-Jun topology and expectation appears to reflect the overlap between c-Jun and a CpG island in most taxa, including crocodilians. This CpG island is absent in the frog and turtle, and convergence in base composition appears to be at least partially responsible for the signal uniting these taxa. Noise reduction approaches can eliminate the unexpected frog-turtle clade, demonstrating that multiple signals are present in the c-Jun alignment. We used phylogenetic methods to visualize these signals; we suggest that examining both historical and non-historical signals will prove important for phylogenomic analyses.

  16. Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses.

    Science.gov (United States)

    O'Connell, Richard J; Thon, Michael R; Hacquard, Stéphane; Amyotte, Stefan G; Kleemann, Jochen; Torres, Maria F; Damm, Ulrike; Buiate, Ester A; Epstein, Lynn; Alkan, Noam; Altmüller, Janine; Alvarado-Balderrama, Lucia; Bauser, Christopher A; Becker, Christian; Birren, Bruce W; Chen, Zehua; Choi, Jaeyoung; Crouch, Jo Anne; Duvick, Jonathan P; Farman, Mark A; Gan, Pamela; Heiman, David; Henrissat, Bernard; Howard, Richard J; Kabbage, Mehdi; Koch, Christian; Kracher, Barbara; Kubo, Yasuyuki; Law, Audrey D; Lebrun, Marc-Henri; Lee, Yong-Hwan; Miyara, Itay; Moore, Neil; Neumann, Ulla; Nordström, Karl; Panaccione, Daniel G; Panstruga, Ralph; Place, Michael; Proctor, Robert H; Prusky, Dov; Rech, Gabriel; Reinhardt, Richard; Rollins, Jeffrey A; Rounsley, Steve; Schardl, Christopher L; Schwartz, David C; Shenoy, Narmada; Shirasu, Ken; Sikhakolli, Usha R; Stüber, Kurt; Sukno, Serenella A; Sweigard, James A; Takano, Yoshitaka; Takahara, Hiroyuki; Trail, Frances; van der Does, H Charlotte; Voll, Lars M; Will, Isa; Young, Sarah; Zeng, Qiandong; Zhang, Jingze; Zhou, Shiguo; Dickman, Martin B; Schulze-Lefert, Paul; Ver Loren van Themaat, Emiel; Ma, Li-Jun; Vaillancourt, Lisa J

    2012-09-01

    Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and transcriptome analyses of Colletotrichum higginsianum infecting Arabidopsis thaliana and Colletotrichum graminicola infecting maize. Comparative genomics showed that both fungi have large sets of pathogenicity-related genes, but families of genes encoding secreted effectors, pectin-degrading enzymes, secondary metabolism enzymes, transporters and peptidases are expanded in C. higginsianum. Genome-wide expression profiling revealed that these genes are transcribed in successive waves that are linked to pathogenic transitions: effectors and secondary metabolism enzymes are induced before penetration and during biotrophy, whereas most hydrolases and transporters are upregulated later, at the switch to necrotrophy. Our findings show that preinvasion perception of plant-derived signals substantially reprograms fungal gene expression and indicate previously unknown functions for particular fungal cell types.

  17. Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Brevik, Erlend J; van Donkelaar, Marjolein M J; Weber, Heike; Sánchez-Mora, Cristina; Jacob, Christian; Rivero, Olga; Kittel-Schneider, Sarah; Garcia-Martínez, Iris; Aebi, Marcel; van Hulzen, Kimm; Cormand, Bru; Ramos-Quiroga, Josep A; Lesch, Klaus-Peter; Reif, Andreas; Ribasés, Marta; Franke, Barbara; Posserud, Maj-Britt; Johansson, Stefan; Lundervold, Astri J; Haavik, Jan; Zayats, Tetyana

    2016-07-01

    Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  18. The Plant Ontology as a Tool for Comparative Plant Anatomy and Genomic Analyses

    Science.gov (United States)

    Cooper, Laurel; Walls, Ramona L.; Elser, Justin; Gandolfo, Maria A.; Stevenson, Dennis W.; Smith, Barry; Preece, Justin; Athreya, Balaji; Mungall, Christopher J.; Rensing, Stefan; Hiss, Manuel; Lang, Daniel; Reski, Ralf; Berardini, Tanya Z.; Li, Donghui; Huala, Eva; Schaeffer, Mary; Menda, Naama; Arnaud, Elizabeth; Shrestha, Rosemary; Yamazaki, Yukiko; Jaiswal, Pankaj

    2013-01-01

    The Plant Ontology (PO; http://www.plantontology.org/) is a publicly available, collaborative effort to develop and maintain a controlled, structured vocabulary (‘ontology’) of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO has been expanded to include all green plants. The PO was the first multispecies anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. As of Release #18 (July 2012), there are about 2.2 million annotations linking PO terms to >110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and quantitative trait loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs. PMID:23220694

  19. The plant ontology as a tool for comparative plant anatomy and genomic analyses.

    Science.gov (United States)

    Cooper, Laurel; Walls, Ramona L; Elser, Justin; Gandolfo, Maria A; Stevenson, Dennis W; Smith, Barry; Preece, Justin; Athreya, Balaji; Mungall, Christopher J; Rensing, Stefan; Hiss, Manuel; Lang, Daniel; Reski, Ralf; Berardini, Tanya Z; Li, Donghui; Huala, Eva; Schaeffer, Mary; Menda, Naama; Arnaud, Elizabeth; Shrestha, Rosemary; Yamazaki, Yukiko; Jaiswal, Pankaj

    2013-02-01

    The Plant Ontology (PO; http://www.plantontology.org/) is a publicly available, collaborative effort to develop and maintain a controlled, structured vocabulary ('ontology') of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO has been expanded to include all green plants. The PO was the first multispecies anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. As of Release #18 (July 2012), there are about 2.2 million annotations linking PO terms to >110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and quantitative trait loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs.

  20. Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris.

    Science.gov (United States)

    Qian, Wei; Jia, Yantao; Ren, Shuang-Xi; He, Yong-Qiang; Feng, Jia-Xun; Lu, Ling-Feng; Sun, Qihong; Ying, Ge; Tang, Dong-Jie; Tang, Hua; Wu, Wei; Hao, Pei; Wang, Lifeng; Jiang, Bo-Le; Zeng, Shenyan; Gu, Wen-Yi; Lu, Gang; Rong, Li; Tian, Yingchuan; Yao, Zhijian; Fu, Gang; Chen, Baoshan; Fang, Rongxiang; Qiang, Boqin; Chen, Zhu; Zhao, Guo-Ping; Tang, Ji-Liang; He, Chaozu

    2005-06-01

    Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.

  1. Phylogenetic analyses of cyanobacterial genomes: Quantification of horizontal gene transfer events

    OpenAIRE

    Zhaxybayeva, Olga; Gogarten, J. Peter; Charlebois, Robert L.; Doolittle, W Ford; Papke, R Thane

    2006-01-01

    Using 1128 protein-coding gene families from 11 completely sequenced cyanobacterial genomes, we attempt to quantify horizontal gene transfer events within cyanobacteria, as well as between cyanobacteria and other phyla. A novel method of detecting and enumerating potential horizontal gene transfer events within a group of organisms based on analyses of “embedded quartets” allows us to identify phylogenetic signal consistent with a plurality of gene families, as well as to delineate cases of c...

  2. Seismic hazard analyses for Taipei city including deaggregation, design spectra, and time history with excel applications

    Science.gov (United States)

    Wang, Jui-Pin; Huang, Duruo; Cheng, Chin-Tung; Shao, Kuo-Shin; Wu, Yuan-Chieh; Chang, Chih-Wei

    2013-03-01

    Given the difficulty of earthquake forecast, Probabilistic Seismic Hazard Analysis (PSHA) has been a method to best estimate site-specific ground motion or response spectra in earthquake engineering and engineering seismology. In this paper, the first in-depth PSHA study for Taipei, the economic center of Taiwan with a six-million population, was carried out. Unlike the very recent PSHA study for Taiwan, this study includes the follow-up hazard deaggregation, response spectra, and the earthquake motion recommendations. Hazard deaggregation results show that moderate-size and near-source earthquakes are the most probable scenario for this city. Moreover, similar to the findings in a few recent studies, the earthquake risk for Taipei should be relatively high and considering this city's importance, the high risk should not be overlooked and a potential revision of the local technical reference would be needed. In addition to the case study, some innovative Excel applications to PSHA are introduced in this paper. Such spreadsheet applications are applicable to geosciences research as those developed for data reduction or quantitative analysis with Excel's user-friendly nature and wide accessibility.

  3. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    Directory of Open Access Journals (Sweden)

    Lisette J. A. Kogelman

    2014-07-01

    Full Text Available Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH and differentially wired (DW networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g. NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways

  4. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses.

    Science.gov (United States)

    Kogelman, Lisette J A; Pant, Sameer D; Fredholm, Merete; Kadarmideen, Haja N

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie

  5. Genomic and peptidomic analyses of the neuropeptides from the emerging pest, Drosophila suzukii.

    Science.gov (United States)

    Audsley, Neil; Down, Rachel E; Isaac, R Elwyn

    2015-06-01

    Drosophila suzukii is a highly polyphagous invasive pest which has been recently introduced into Europe and North America, where it is causing severe economic losses through larval infestations of stone and berry fruits. The peptidome of the selected nervous tissues of adult D. suzukii was investigated as a first step in identifying potential targets for the development of novel insecticides. Through in silico analyses of the D. suzukii genome databases 28 neuropeptide families, comprising more than 70 predicted peptides were identified. Using a combination of liquid chromatography and mass spectrometry of tissue extracts, 33 predicted peptides, representing 15 different peptide families were identified by their molecular masses and a total of 17 peptide sequences were confirmed by ion fragmentation. A comparison between the peptides and precursors of D. suzukii and D. melanogaster shows they are highly conserved, with differences only identified in the amino acid sequences of the peptides encoded in the FMRFamide, hugin and ecydysis triggering hormone precursors. All other peptides predicted and identified from D. suzukii appear to be identical to those previously characterized from D. melanogaster. Adipokinetic hormone was only identified in the corpus cardiacum, other peptides present included short neuropeptide F, a pyrokinin and myosuppressin, the latter of which was the only peptide identified from the crop nerve bundle. Peptides present in extracts of the brain and/or thoracico-abdominal ganglion included allatostatins, cardioacceleratory peptide 2b, corazonin, extended FMRFamides, pyrokinins, myoinihibitory peptides, neuropeptide-like precursor 1, SIFamide, short neuropeptide F, kinin, sulfakinins and tachykinin related peptides. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  6. Comparative analyses of the complete mitochondrial genomes of Ascaris lumbricoides and Ascaris suum from humans and pigs.

    Science.gov (United States)

    Liu, Guo-Hua; Wu, Chang-Yi; Song, Hui-Qun; Wei, Shu-Jun; Xu, Min-Jun; Lin, Rui-Qing; Zhao, Guang-Hui; Huang, Si-Yang; Zhu, Xing-Quan

    2012-01-15

    Ascaris lumbricoides and Ascaris suum are parasitic nematodes living in the small intestine of humans and pigs, and can cause the disease ascariasis. For long, there has been controversy as to whether the two ascaridoid taxa represent the same species due to their significant resemblances in morphology. However, the complete mitochondrial (mt) genome data have been lacking for A. lumbricoides in spite of human and animal health significance and socio-economic impact globally of these parasites. In the present study, we sequenced the complete mt genomes of A. lumbricoides and A. suum (China isolate), which was 14,303 bp and 14,311 bp in size, respectively. The identity of the mt genomes was 98.1% between A. lumbricoides and A. suum (China isolate), and 98.5% between A. suum (China isolate) and A. suum (USA isolate). Both genomes are circular, and consist of 36 genes, including 12 genes for proteins, 2 genes for rRNA and 22 genes for tRNA, which are consistent with that of all other species of ascaridoid studied to date. All genes are transcribed in the same direction and have a nucleotide composition high in A and T (71.7% for A. lumbricoides and 71.8% for A. suum). The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. Phylogenetic analyses of A. lumbricoides and A. suum using concatenated amino acid sequences of 12 protein-coding genes, with three different computational algorithms (Bayesian analysis, maximum likelihood and maximum parsimony) all clustered in a clade with high statistical support, indicating that A. lumbricoides and A. suum was very closely related. These mt genome data and the results provide some additional genetic evidence that A. lumbricoides and A. suum may represent the same species. The mt genome data presented in this study are also useful novel markers for studying the molecular epidemiology and population genetics of Ascaris.

  7. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    DEFF Research Database (Denmark)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted...... genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated...... with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us...

  8. The mitochondrial genome of Atrijuglans hetaohei Yang (Lepidoptera: Gelechioidea) and related phylogenetic analyses.

    Science.gov (United States)

    Wang, Qiqi; Zhang, Zhengqing; Tang, Guanghui

    2016-04-25

    Complete mitochondrial genome sequences are of great importance for better understanding the genome-level characteristics and phylogenetic relationships among related species. In this study, the complete mitochondrial genome of Atrijuglans hetaohei Yang is sequenced and analyzed, which is 15,379bp in length (GenBank: KT581634) and contains a typical set of 13 protein-coding genes, 22 tRNA genes, two rRNA genes and a non-coding region (control region). Except for cox1 gene that is initiated by CGA codon, all protein-coding genes start with ATN codons and end with the stop codon T, TA or TAA. All tRNAs have a typical clover-leaf secondary structure, except for trnS1, of which the DHU arm could not form a stable stem-loop structure. The secondary structure of rrnL and rrnS consists of 49 helices and 33 helices, respectively. Phylogenetic analyses of the complete mitochondrial genome sequences and of the amino acid sequences for 13 mitochondrial protein-coding genes among related species support the view that A. hetaohei is more closely related to the Gelechioidea than Yponomeutoidea. This result is consistent with a previous classification based on morphology.

  9. Matching of array CGH and gene expression microarray features for the purpose of integrative genomic analyses

    Directory of Open Access Journals (Sweden)

    van Wieringen Wessel N

    2012-05-01

    Full Text Available Abstract Background An increasing number of genomic studies interrogating more than one molecular level is published. Bioinformatics follows biological practice, and recent years have seen a surge in methodology for the integrative analysis of genomic data. Often such analyses require knowledge of which elements of one platform link to those of another. Although important, many integrative analyses do not or insufficiently detail the matching of the platforms. Results We describe, illustrate and discuss six matching procedures. They are implemented in the R-package sigaR (available from Bioconductor. The principles underlying the presented matching procedures are generic, and can be combined to form new matching approaches or be applied to the matching of other platforms. Illustration of the matching procedures on a variety of data sets reveals how the procedures differ in the use of the available data, and may even lead to different results for individual genes. Conclusions Matching of data from multiple genomics platforms is an important preprocessing step for many integrative bioinformatic analysis, for which we present six generic procedures, both old and new. They have been implemented in the R-package sigaR, available from Bioconductor.

  10. Genome-wide analyses for dissecting gene regulatory networks in the shoot apical meristem.

    Science.gov (United States)

    Bustamante, Mariana; Matus, José Tomás; Riechmann, José Luis

    2016-03-01

    Shoot apical meristem activity is controlled by complex regulatory networks in which components such as transcription factors, miRNAs, small peptides, hormones, enzymes and epigenetic marks all participate. Many key genes that determine the inherent characteristics of the shoot apical meristem have been identified through genetic approaches. Recent advances in genome-wide studies generating extensive transcriptomic and DNA-binding datasets have increased our understanding of the interactions within the regulatory networks that control the activity of the meristem, identifying new regulators and uncovering connections between previously unlinked network components. In this review, we focus on recent studies that illustrate the contribution of whole genome analyses to understand meristem function. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. The complete mitochondrial genome of Trabala vishnou guttata (Lepidoptera: Lasiocampidae) and the related phylogenetic analyses.

    Science.gov (United States)

    Wu, Liuyu; Xiong, Xiao; Wang, Xuming; Xin, Tianrong; Wang, Jing; Zou, Zhiwen; Xia, Bin

    2016-12-01

    The bluish yellow lappet moth, Trabala vishnou guttata is an extraordinarily important pest in China. The complete mitochondrial genome is sequenced and determined firstly, which is based on traditional PCR amplification and primer walking methods with a length of 15,281 bp, including 13 protein-coding (PCG) genes, 22 transfer RNA (rRNA) genes, two ribosomal RNA (tRNA) genes, and an A + T-rich region. The gene order and orientation of the T. vishnou guttata mitogenome were identical to the other sequenced Lasiocampidae species. The overall nucleotide composition of T. vishnou guttata is A (40.27 %), T (40.59 %), C (11.58 %) and G (7.56 %), respectively. All the PCGs initiate with the three orthodox start codons ATN except for coxI with CGA start codon. Three PCGs (coxI, coxII and nad4) used incomplete stop codon T, while the other 10 PCGs terminate with complete stop codon TAA. All tRNA genes have a typical clover-leaf structure except for the absence of a dihydrouridine arm in trnS (AGN). The length of A + T-rich region is 383 bp. Phylogeny is established to reveal the genetic relationship between T. vishnou guttata and other lepidopteran species based on 13 PCGs nucleotide sequences of the sequenced species (32 taxa) by Maximum likelihood and Bayesian methods. Phylogenetic analyses presents that T. vishnou guttata and its closely related species (Dendrolimus taxa) are clustered on Lasiocampidae group. It is a sister clade relationship between Lasiocampidae and other families in Bombycoidea with a bootstrap value of 83 % and a posterior probability of 0.75. This study supports that Lasiocampidae may be independent from Bombycoidea.

  12. Genomic analyses of the microsporidian Nosema ceranae, an emergent pathogen of honey bees.

    Directory of Open Access Journals (Sweden)

    R Scott Cornman

    2009-06-01

    Full Text Available Recent steep declines in honey bee health have severely impacted the beekeeping industry, presenting new risks for agricultural commodities that depend on insect pollination. Honey bee declines could reflect increased pressures from parasites and pathogens. The incidence of the microsporidian pathogen Nosema ceranae has increased significantly in the past decade. Here we present a draft assembly (7.86 MB of the N. ceranae genome derived from pyrosequence data, including initial gene models and genomic comparisons with other members of this highly derived fungal lineage. N. ceranae has a strongly AT-biased genome (74% A+T and a diversity of repetitive elements, complicating the assembly. Of 2,614 predicted protein-coding sequences, we conservatively estimate that 1,366 have homologs in the microsporidian Encephalitozoon cuniculi, the most closely related published genome sequence. We identify genes conserved among microsporidia that lack clear homology outside this group, which are of special interest as potential virulence factors in this group of obligate parasites. A substantial fraction of the diminutive N. ceranae proteome consists of novel and transposable-element proteins. For a majority of well-supported gene models, a conserved sense-strand motif can be found within 15 bases upstream of the start codon; a previously uncharacterized version of this motif is also present in E. cuniculi. These comparisons provide insight into the architecture, regulation, and evolution of microsporidian genomes, and will drive investigations into honey bee-Nosema interactions.

  13. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations

    Science.gov (United States)

    Keane, Michael; Craig, Thomas; Alföldi, Jessica; Berlin, Aaron M.; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M.; de Magalhães, João Pedro

    2014-01-01

    Motivation: The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. Results: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat’s extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource (http://www.naked-mole-rat.org), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species. Availability and implementation: The Naked Mole Rat Genome Resource is freely available online at http://www.naked-mole-rat.org. This resource is open source and the source code is available at https://github.com/maglab/naked-mole-rat-portal. Contact: jp@senescence.info PMID:25172923

  14. [Pathological Diagnoses and Whole-genome Sequence Analyses of the Jaagsiekte Sheep Retrovirus in Xinjiang, China].

    Science.gov (United States)

    Yang, Sufang; Liang, Tian; Zhao, Qingliang; Zhang, Dianqing; Si Junqiang; Zhang, Jing; Yang, Xia; Sheng, Jinliang

    2015-05-01

    To carry out pathologic diagnoses and whole-genome sequence analyses of the Jaagsiekte sheep retrovirus (JSRV) in Xinjiang, China, we first observed sheep suspected to have the JSRV. Then, the extracted virus suspension was observed by transmission electron microscopy (TEM). Total RNAs from lungs of JSRV-infected sheep were extracted and reverse-transcribed using a cDNA synthesis kit. Six pairs of primers were designed according to the exogenous reference virus strain (AF105220). Reverse transcription-polymerase chain reaction was carried out from JSRV-infected tissue, and the whole genome of the JSRV sequenced. Our results showed: flow of nasal fluid ("wheelbarrow test"); different sizes of adenoma lesions in the lungs; papillary hyperplasia of alveolar epithelial cells; alveolar cavity filled with macrophages; dissolute nuclei in central lesions. TEM revealed JSRV particles with a diameter of 88 nm to 125. 4 nm. The full-length of the viral genome sequence was 7456 bp. BLAST analyses showed nucleotide homology of 96% and 95% compared with that of the representative strain from the USA (AF105220) and UK (AF357971). Nucleotide homology was 89.8% and 89.9% compared with the endogenous Jaagsiekte sheep retrovirus, Inner Mongolia strain (DQ838493) and USA strain (EF680300). The specific pathogenic amino-acid sequence "YXXM" was found in the TM district, similar to the exogenous JSRV: this gene has been reported to be oncogenic. This is the first report of the complete genomic sequence of the exogenous JSRV from Xinjiang, and could lay the foundation for study of the biological characteristics and pathogenic mechanisms of the pulmonary adenomatosis virus in sheep.

  15. Genomic sequencing and analyses of HearMNPV—a new Multinucleocapsid nucleopolyhedrovirus isolated from Helicoverpa armigera

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    Tang Ping

    2012-08-01

    Full Text Available Abstract Background HearMNPV, a nucleopolyhedrovirus (NPV, which infects the cotton bollworm, Helicoverpa armigera, comprises multiple rod-shaped nucleocapsids in virion(as detected by electron microscopy. HearMNPV shows a different host range compared with H. armigera single-nucleocapsid NPV (HearSNPV. To better understand HearMNPV, the HearMNPV genome was sequenced and analyzed. Methods The morphology of HearMNPV was observed by electron microscope. The qPCR was used to determine the replication kinetics of HearMNPV infectious for H. armigera in vivo. A random genomic library of HearMNPV was constructed according to the “partial filling-in” method, the sequence and organization of the HearMNPV genome was analyzed and compared with sequence data from other baculoviruses. Results Real time qPCR showed that HearMNPV DNA replication included a decreasing phase, latent phase, exponential phase, and a stationary phase during infection of H. armigera. The HearMNPV genome consists of 154,196 base pairs, with a G + C content of 40.07%. 162 putative ORFs were detected in the HearMNPV genome, which represented 90.16% of the genome. The remaining 9.84% constitute four homologous regions and other non-coding regions. The gene content and gene arrangement in HearMNPV were most similar to those of Mamestra configurata NPV-B (MacoNPV-B, but was different to HearSNPV. Comparison of the genome of HearMNPV and MacoNPV-B suggested that HearMNPV has a deletion of a 5.4-kb fragment containing five ORFs. In addition, HearMNPV orf66, bro genes, and hrs are different to the corresponding parts of the MacoNPV-B genome. Conclusions HearMNPV can replicate in vivo in H. armigera and in vitro, and is a new NPV isolate distinguished from HearSNPV. HearMNPV is most closely related to MacoNPV-B, but has a distinct genomic structure, content, and organization.

  16. Genomic Characterization of Two Novel SAR11 Isolates From the Red Sea, Including the First Strain of the SAR11 Ib clade

    KAUST Repository

    Jimenez Infante, Francy M.

    2017-06-22

    The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea, one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain-specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter.

  17. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency

    Science.gov (United States)

    Frankowiack, Marcel; Kierczak, Marcin; Bergvall, Kerstin; Axelsson, Erik; Tintle, Linda; Marti, Eliane; Roosje, Petra; Leeb, Tosso; Hedhammar, Åke; Hammarström, Lennart; Lindblad-Toh, Kerstin

    2015-01-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development. PMID:26225558

  18. Familial and genomic analyses of postural changes in systolic and diastolic blood pressure.

    Science.gov (United States)

    Harrap, Stephen B; Cui, Jisheng S; Wong, Zilla Y H; Hopper, John L

    2004-03-01

    The physiological adaptation to the erect posture involves integrated neural and cardiovascular responses that might be determined by genetic factors. We examined the familial- and individual-specific components of variance for postural changes in systolic and diastolic blood pressure in 767 volunteer nuclear adult families from the Victorian Family Heart Study. In 274 adult sibling pairs, we made a genome-wide scan using 400 markers for quantitative trait loci linked with the postural changes in systolic and diastolic pressures. Overall, systolic pressure did not change on standing, but there was considerable variation in this phenotype (SD=8.1 mm Hg). Familial analyses revealed that 25% of the variance of change in systolic pressure was attributable to genetic factors. In contrast, diastolic pressure increased by 6.3 mm Hg (SD=7.0 mm Hg) on standing and there was no evidence of contributory genetic factors. Multipoint quantitative genome linkage mapping suggested evidence (Z=3.2) of linkage of the postural change in systolic pressure to chromosome 12 but found no genome-wide evidence of linkage for the change in diastolic pressure. These findings suggest that genetic factors determine whether systolic pressure decreases or increases when one stands, possibly as the result of unidentified alleles on chromosome 12. The genetics of postural changes in systolic blood pressure might reflect the general buffering function of the baroreflex; thereby, the predisposition to sudden decreases or increases in systolic pressure might cause postural hypotension or vessel wall disruption, respectively.

  19. Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper

    Science.gov (United States)

    Yin, Wei; Wang, Zong-ji; Li, Qi-ye; Lian, Jin-ming; Zhou, Yang; Lu, Bing-zheng; Jin, Li-jun; Qiu, Peng-xin; Zhang, Pei; Zhu, Wen-bo; Wen, Bo; Huang, Yi-jun; Lin, Zhi-long; Qiu, Bi-tao; Su, Xing-wen; Yang, Huan-ming; Zhang, Guo-jie; Yan, Guang-mei; Zhou, Qi

    2016-01-01

    Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution. PMID:27708285

  20. Aye-aye population genomic analyses highlight an important center of endemism in northern Madagascar.

    Science.gov (United States)

    Perry, George H; Louis, Edward E; Ratan, Aakrosh; Bedoya-Reina, Oscar C; Burhans, Richard C; Lei, Runhua; Johnson, Steig E; Schuster, Stephan C; Miller, Webb

    2013-04-09

    We performed a population genomics study of the aye-aye, a highly specialized nocturnal lemur from Madagascar. Aye-ayes have low population densities and extensive range requirements that could make this flagship species particularly susceptible to extinction. Therefore, knowledge of genetic diversity and differentiation among aye-aye populations is critical for conservation planning. Such information may also advance our general understanding of Malagasy biogeography, as aye-ayes have the largest species distribution of any lemur. We generated and analyzed whole-genome sequence data for 12 aye-ayes from three regions of Madagascar (North, West, and East). We found that the North population is genetically distinct, with strong differentiation from other aye-ayes over relatively short geographic distances. For comparison, the average FST value between the North and East aye-aye populations--separated by only 248 km--is over 2.1-times greater than that observed between human Africans and Europeans. This finding is consistent with prior watershed- and climate-based hypotheses of a center of endemism in northern Madagascar. Taken together, these results suggest a strong and long-term biogeographical barrier to gene flow. Thus, the specific attention that should be directed toward preserving large, contiguous aye-aye habitats in northern Madagascar may also benefit the conservation of other distinct taxonomic units. To help facilitate future ecological- and conservation-motivated population genomic analyses by noncomputational biologists, the analytical toolkit used in this study is available on the Galaxy Web site.

  1. A new database (GCD) on genome composition for eukaryote and prokaryote genome sequences and their initial analyses.

    Science.gov (United States)

    Kryukov, Kirill; Sumiyama, Kenta; Ikeo, Kazuho; Gojobori, Takashi; Saitou, Naruya

    2012-01-01

    Eukaryote genomes contain many noncoding regions, and they are quite complex. To understand these complexities, we constructed a database, Genome Composition Database, for the whole genome composition statistics for 101 eukaryote genome data, as well as more than 1,000 prokaryote genomes. Frequencies of all possible one to ten oligonucleotides were counted for each genome, and these observed values were compared with expected values computed under observed oligonucleotide frequencies of length 1-4. Deviations from expected values were much larger for eukaryotes than prokaryotes, except for fungal genomes. Mammalian genomes showed the largest deviation among animals. The results of comparison are available online at http://esper.lab.nig.ac.jp/genome-composition-database/.

  2. Deciphering heterogeneity in pig genome assembly Sscrofa9 by isochore and isochore-like region analyses.

    Directory of Open Access Journals (Sweden)

    Wenqian Zhang

    Full Text Available BACKGROUND: The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes. Although the isochore has been widely studied in humans and other species, little is known about its distribution in pigs. PRINCIPAL FINDINGS: In this paper, we construct a map of long homogeneous genome regions (LHGRs, i.e., isochores and isochore-like regions, in pigs to provide an intuitive version of GC heterogeneity in each chromosome. The LHGR pattern study not only quantifies heterogeneities, but also reveals some primary characteristics of the chromatin organization, including the followings: (1 the majority of LHGRs belong to GC-poor families and are in long length; (2 a high gene density tends to occur with the appearance of GC-rich LHGRs; and (3 the density of LINE repeats decreases with an increase in the GC content of LHGRs. Furthermore, a portion of LHGRs with particular GC ranges (50%-51% and 54%-55% tend to have abnormally high gene densities, suggesting that biased gene conversion (BGC, as well as time- and energy-saving principles, could be of importance to the formation of genome organization. CONCLUSION: This study significantly improves our knowledge of chromatin organization in the pig genome. Correlations between the different biological features (e.g., gene density and repeat density and GC content of LHGRs provide a unique glimpse of in silico gene and repeats prediction.

  3. Genome-wide association and linkage analyses localize a progressive retinal atrophy locus in Persian cats.

    Science.gov (United States)

    Alhaddad, Hasan; Gandolfi, Barbara; Grahn, Robert A; Rah, Hyung-Chul; Peterson, Carlyn B; Maggs, David J; Good, Kathryn L; Pedersen, Niels C; Lyons, Leslie A

    2014-08-01

    Hereditary eye diseases of animals serve as excellent models of human ocular disorders and assist in the development of gene and drug therapies for inherited forms of blindness. Several primary hereditary eye conditions affecting various ocular tissues and having different rates of progression have been documented in domestic cats. Gene therapy for canine retinopathies has been successful, thus the cat could be a gene therapy candidate for other forms of retinal degenerations. The current study investigates a hereditary, autosomal recessive, retinal degeneration specific to Persian cats. A multi-generational pedigree segregating for this progressive retinal atrophy was genotyped using a 63 K SNP array and analyzed via genome-wide linkage and association methods. A multi-point parametric linkage analysis localized the blindness phenotype to a ~1.75 Mb region with significant LOD scores (Z ≈ 14, θ = 0.00) on cat chromosome E1. Genome-wide TDT, sib-TDT, and case-control analyses also consistently supported significant association within the same region on chromosome E1, which is homologous to human chromosome 17. Using haplotype analysis, a ~1.3 Mb region was identified as highly associated for progressive retinal atrophy in Persian cats. Several candidate genes within the region are reasonable candidates as a potential causative gene and should be considered for molecular analyses.

  4. Emergence and evolutionary analysis of the human DDR network: implications in comparative genomics and downstream analyses.

    Science.gov (United States)

    Arcas, Aida; Fernández-Capetillo, Oscar; Cases, Ildefonso; Rojas, Ana M

    2014-04-01

    The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies.

  5. Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent Anomalurus

    Directory of Open Access Journals (Sweden)

    Gissi Carmela

    2007-02-01

    Full Text Available Abstract Background Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious. Results We have sequenced and performed extensive evolutionary analyses on the mitochondrial genome of the scaly-tailed flying squirrel Anomalurus sp., an enigmatic rodent whose phylogenetic affinities have been obscure and extensively debated. Our phylogenetic analyses of the coding regions of available complete mitochondrial genome sequences from Euarchontoglires suggest that Anomalurus is a sister taxon to the Hystricognathi, and that this clade represents the most basal divergence among sampled Rodentia. Bayesian dating methods incorporating a relaxed molecular clock provide divergence-time estimates which are consistently in agreement with the fossil record and which indicate a rapid radiation within Glires around 60 million years ago. Conclusion Taken together, the data presented provide a working hypothesis as to the phylogenetic placement of Anomalurus, underline the utility of mitochondrial sequences in the resolution of even relatively deep divergences and go some way to explaining the difficulty of conclusively resolving higher-level relationships within Glires with available data and methodologies.

  6. Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation.

    Directory of Open Access Journals (Sweden)

    Jinkui Yang

    2011-09-01

    Full Text Available Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927 was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.

  7. Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

  8. Widespread occurrence of organelle genome-encoded 5S rRNAs including permuted molecules.

    Science.gov (United States)

    Valach, Matus; Burger, Gertraud; Gray, Michael W; Lang, B Franz

    2014-12-16

    5S Ribosomal RNA (5S rRNA) is a universal component of ribosomes, and the corresponding gene is easily identified in archaeal, bacterial and nuclear genome sequences. However, organelle gene homologs (rrn5) appear to be absent from most mitochondrial and several chloroplast genomes. Here, we re-examine the distribution of organelle rrn5 by building mitochondrion- and plastid-specific covariance models (CMs) with which we screened organelle genome sequences. We not only recover all organelle rrn5 genes annotated in GenBank records, but also identify more than 50 previously unrecognized homologs in mitochondrial genomes of various stramenopiles, red algae, cryptomonads, malawimonads and apusozoans, and surprisingly, in the apicoplast (highly derived plastid) genomes of the coccidian pathogens Toxoplasma gondii and Eimeria tenella. Comparative modeling of RNA secondary structure reveals that mitochondrial 5S rRNAs from brown algae adopt a permuted triskelion shape that has not been seen elsewhere. Expression of the newly predicted rrn5 genes is confirmed experimentally in 10 instances, based on our own and published RNA-Seq data. This study establishes that particularly mitochondrial 5S rRNA has a much broader taxonomic distribution and a much larger structural variability than previously thought. The newly developed CMs will be made available via the Rfam database and the MFannot organelle genome annotator. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Genome-wide meta-analyses of smoking behaviors in African Americans.

    Science.gov (United States)

    David, S P; Hamidovic, A; Chen, G K; Bergen, A W; Wessel, J; Kasberger, J L; Brown, W M; Petruzella, S; Thacker, E L; Kim, Y; Nalls, M A; Tranah, G J; Sung, Y J; Ambrosone, C B; Arnett, D; Bandera, E V; Becker, D M; Becker, L; Berndt, S I; Bernstein, L; Blot, W J; Broeckel, U; Buxbaum, S G; Caporaso, N; Casey, G; Chanock, S J; Deming, S L; Diver, W R; Eaton, C B; Evans, D S; Evans, M K; Fornage, M; Franceschini, N; Harris, T B; Henderson, B E; Hernandez, D G; Hitsman, B; Hu, J J; Hunt, S C; Ingles, S A; John, E M; Kittles, R; Kolb, S; Kolonel, L N; Le Marchand, L; Liu, Y; Lohman, K K; McKnight, B; Millikan, R C; Murphy, A; Neslund-Dudas, C; Nyante, S; Press, M; Psaty, B M; Rao, D C; Redline, S; Rodriguez-Gil, J L; Rybicki, B A; Signorello, L B; Singleton, A B; Smoller, J; Snively, B; Spring, B; Stanford, J L; Strom, S S; Swan, G E; Taylor, K D; Thun, M J; Wilson, A F; Witte, J S; Yamamura, Y; Yanek, L R; Yu, K; Zheng, W; Ziegler, R G; Zonderman, A B; Jorgenson, E; Haiman, C A; Furberg, H

    2012-05-22

    The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

  10. Endophytic life strategies decoded by genome and transcriptome analyses of the mutualistic root symbiont Piriformospora indica.

    Directory of Open Access Journals (Sweden)

    Alga Zuccaro

    2011-10-01

    Full Text Available Recent sequencing projects have provided deep insight into fungal lifestyle-associated genomic adaptations. Here we report on the 25 Mb genome of the mutualistic root symbiont Piriformospora indica (Sebacinales, Basidiomycota and provide a global characterization of fungal transcriptional responses associated with the colonization of living and dead barley roots. Extensive comparative analysis of the P. indica genome with other Basidiomycota and Ascomycota fungi that have diverse lifestyle strategies identified features typically associated with both, biotrophism and saprotrophism. The tightly controlled expression of the lifestyle-associated gene sets during the onset of the symbiosis, revealed by microarray analysis, argues for a biphasic root colonization strategy of P. indica. This is supported by a cytological study that shows an early biotrophic growth followed by a cell death-associated phase. About 10% of the fungal genes induced during the biotrophic colonization encoded putative small secreted proteins (SSP, including several lectin-like proteins and members of a P. indica-specific gene family (DELD with a conserved novel seven-amino acids motif at the C-terminus. Similar to effectors found in other filamentous organisms, the occurrence of the DELDs correlated with the presence of transposable elements in gene-poor repeat-rich regions of the genome. This is the first in depth genomic study describing a mutualistic symbiont with a biphasic lifestyle. Our findings provide a significant advance in understanding development of biotrophic plant symbionts and suggest a series of incremental shifts along the continuum from saprotrophy towards biotrophy in the evolution of mycorrhizal association from decomposer fungi.

  11. The Drosophila genome nexus: a population genomic resource of 623 Drosophila melanogaster genomes, including 197 from a single ancestral range population.

    Science.gov (United States)

    Lack, Justin B; Cardeno, Charis M; Crepeau, Marc W; Taylor, William; Corbett-Detig, Russell B; Stevens, Kristian A; Langley, Charles H; Pool, John E

    2015-04-01

    Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets. Copyright © 2015 by the Genetics Society of America.

  12. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution.

    Science.gov (United States)

    Palmenberg, Ann C; Spiro, David; Kuzmickas, Ryan; Wang, Shiliang; Djikeng, Appolinaire; Rathe, Jennifer A; Fraser-Liggett, Claire M; Liggett, Stephen B

    2009-04-03

    Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5' untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.

  13. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.

    Science.gov (United States)

    Hancock, Dana B; Eijgelsheim, Mark; Wilk, Jemma B; Gharib, Sina A; Loehr, Laura R; Marciante, Kristin D; Franceschini, Nora; van Durme, Yannick M T A; Chen, Ting-Hsu; Barr, R Graham; Schabath, Matthew B; Couper, David J; Brusselle, Guy G; Psaty, Bruce M; van Duijn, Cornelia M; Rotter, Jerome I; Uitterlinden, André G; Hofman, Albert; Punjabi, Naresh M; Rivadeneira, Fernando; Morrison, Alanna C; Enright, Paul L; North, Kari E; Heckbert, Susan R; Lumley, Thomas; Stricker, Bruno H C; O'Connor, George T; London, Stephanie J

    2010-01-01

    Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV(1)) and its ratio to forced vital capacity (FEV(1)/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV(1)/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV(1) (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.

  14. Natural killer cells: from CD3(-)NKp46(+) to post-genomics meta-analyses.

    Science.gov (United States)

    Walzer, Thierry; Jaeger, Sébastien; Chaix, Julie; Vivier, Eric

    2007-06-01

    The original definition of NK cells was based on their 'natural' cytolytic response against tumor cells and virus-infected cells in the absence of specific immunization. However, the term 'natural killer' reflects neither the education/maturation requirements before NK cells can kill nor the entirety of their biological functions. In light of new functional assays, genetic models and genomics analysis, we propose a more accurate definition of NK cells. This definition includes the phenotypical identification of NK cells as CD3(-)NKp46(+) cells across mammalian species. In general, this attempt to redefine NK cells also highlights the need to update the operational definition of cell types in the post-genomic area.

  15. Complete mitochondrial genome sequences of three bats species and whole genome mitochondrial analyses reveal patterns of codon bias and lend support to a basal split in Chiroptera.

    Science.gov (United States)

    Meganathan, P R; Pagan, Heidi J T; McCulloch, Eve S; Stevens, Richard D; Ray, David A

    2012-01-15

    Order Chiroptera is a unique group of mammals whose members have attained self-powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes.

  16. Analyses of the complete genome and gene expression of chloroplast of sweet potato [Ipomoea batata].

    Science.gov (United States)

    Yan, Lang; Lai, Xianjun; Li, Xuedan; Wei, Changhe; Tan, Xuemei; Zhang, Yizheng

    2015-01-01

    Sweet potato [Ipomoea batatas (L.) Lam] ranks among the top seven most important food crops cultivated worldwide and is hexaploid plant (2n=6x=90) in the Convolvulaceae family with a genome size between 2,200 to 3,000 Mb. The genomic resources for this crop are deficient due to its complicated genetic structure. Here, we report the complete nucleotide sequence of the chloroplast (cp) genome of sweet potato, which is a circular molecule of 161,303 bp in the typical quadripartite structure with large (LSC) and small (SSC) single-copy regions separated by a pair of inverted repeats (IRs). The chloroplast DNA contains a total of 145 genes, including 94 protein-encoding genes of which there are 72 single-copy and 11 double-copy genes. The organization and structure of the chloroplast genome (gene content and order, IR expansion/contraction, random repeating sequences, structural rearrangement) of sweet potato were compared with those of Ipomoea (L.) species and some basal important angiosperms, respectively. Some boundary gene-flow and gene gain-and-loss events were identified at intra- and inter-species levels. In addition, by comparing with the transcriptome sequences of sweet potato, the RNA editing events and differential expressions of the chloroplast functional-genes were detected. Moreover, phylogenetic analysis was conducted based on 77 protein-coding genes from 33 taxa and the result may contribute to a better understanding of the evolution progress of the genus Ipomoea (L.), including phylogenetic relationships, intraspecific differentiation and interspecific introgression.

  17. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Science.gov (United States)

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  18. Comparative Chloroplast Genome Analyses of Streptophyte Green Algae Uncover Major Structural Alterations in the Klebsormidiophyceae, Coleochaetophyceae and Zygnematophyceae.

    Science.gov (United States)

    Lemieux, Claude; Otis, Christian; Turmel, Monique

    2016-01-01

    The Streptophyta comprises all land plants and six main lineages of freshwater green algae: Mesostigmatophyceae, Chlorokybophyceae, Klebsormidiophyceae, Charophyceae, Coleochaetophyceae and Zygnematophyceae. Previous comparisons of the chloroplast genome from nine streptophyte algae (including four zygnematophyceans) revealed that, although land plant chloroplast DNAs (cpDNAs) inherited most of their highly conserved structural features from green algal ancestors, considerable cpDNA changes took place during the evolution of the Zygnematophyceae, the sister group of land plants. To gain deeper insights into the evolutionary dynamics of the chloroplast genome in streptophyte algae, we sequenced the cpDNAs of nine additional taxa: two klebsormidiophyceans (Entransia fimbriata and Klebsormidium sp. SAG 51.86), one coleocheatophycean (Coleochaete scutata) and six zygnematophyceans (Cylindrocystis brebissonii, Netrium digitus, Roya obtusa, Spirogyra maxima, Cosmarium botrytis and Closterium baillyanum). Our comparative analyses of these genomes with their streptophyte algal counterparts indicate that the large inverted repeat (IR) encoding the rDNA operon experienced loss or expansion/contraction in all three sampled classes and that genes were extensively shuffled in both the Klebsormidiophyceae and Zygnematophyceae. The klebsormidiophycean genomes boast greatly expanded IRs, with the Entransia 60,590-bp IR being the largest known among green algae. The 206,025-bp Entransia cpDNA, which is one of the largest genome among streptophytes, encodes 118 standard genes, i.e., four additional genes compared to its Klebsormidium flaccidum homolog. We inferred that seven of the 21 group II introns usually found in land plants were already present in the common ancestor of the Klebsormidiophyceae and its sister lineages. At 107,236 bp and with 117 standard genes, the Coleochaete IR-less genome is both the smallest and most compact among the streptophyte algal cpDNAs analyzed thus

  19. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    LENUS (Irish Health Repository)

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  20. Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

    Science.gov (United States)

    Jaratlerdsiri, Weerachai; Deakin, Janine; Godinez, Ricardo M; Shan, Xueyan; Peterson, Daniel G; Marthey, Sylvain; Lyons, Eric; McCarthy, Fiona M; Isberg, Sally R; Higgins, Damien P; Chong, Amanda Y; John, John St; Glenn, Travis C; Ray, David A; Gongora, Jaime

    2014-01-01

    The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer) than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity) with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

  1. Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

    Directory of Open Access Journals (Sweden)

    Weerachai Jaratlerdsiri

    Full Text Available The major histocompatibility complex (MHC is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

  2. Genome-Wide Identification, Evolutionary, and Expression Analyses of Histone H3 Variants in Plants

    Directory of Open Access Journals (Sweden)

    Jinteng Cui

    2015-01-01

    Full Text Available Histone variants alter the nucleosome structure and play important roles in chromosome segregation, transcription, DNA repair, and sperm compaction. Histone H3 is encoded by many genes in most eukaryotic species and is the histone that contains the largest variety of posttranslational modifications. Compared with the metazoan H3 variants, little is known about the complex evolutionary history of H3 variants proteins in plants. Here, we study the identification, evolutionary, and expression analyses of histone H3 variants from genomes in major branches in the plant tree of life. Firstly we identified all the histone three related (HTR genes from the examined genomes, then we classified the four groups variants: centromeric H3, H3.1, H3.3 and H3-like, by phylogenetic analysis, intron information, and alignment. We further demonstrated that the H3 variants have evolved under strong purifying selection, indicating the conservation of HTR proteins. Expression analysis revealed that the HTR has a wide expression profile in maize and rice development and plays important roles in development.

  3. Molecular analyses of mitochondrial pseudogenes within the nuclear genome of arvicoline rodents.

    Science.gov (United States)

    Triant, Deborah A; DeWoody, J Andrew

    2008-01-01

    Nuclear sequences of mitochondrial origin (numts) are common among animals and plants. The mechanism(s) by which numts transfer from the mitochondrion to the nucleus is uncertain, but their insertions may be mediated in part by chromosomal repair mechanisms. If so, then lineages where chromosomal rearrangements are common should be good models for the study of numt evolution. Arvicoline rodents are known for their karyotypic plasticity and numt pseudogenes have been discovered in this group. Here, we characterize a 4 kb numt pseudogene in the arvicoline vole Microtus rossiaemeridionalis. This sequence is among the largest numts described for a mammal lacking a completely sequenced genome. It encompasses three protein-coding and six tRNA pseudogenes that span approximately 25% of the entire mammalian mitochondrial genome. It is bordered by a dinucleotide microsatellite repeat and contains four transposable elements within its sequence and flanking regions. To determine the phylogenetic distribution of this numt among the arvicolines, we characterized one of the mitochondrial pseudogenes (cytochrome b) in 21 additional arvicoline species. Average rates of nucleotide substitution in this arvicoline pseudogene are estimated as 2.3 x 10(-8) substitutions/per site/per year. Furthermore, we performed comparative analyses among all species to estimate the age of this mitochondrial transfer at nearly 4 MYA, predating the origin of most arvicolines.

  4. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    Science.gov (United States)

    Liu, Guodong; Zhang, Lei; Wei, Xiaomin; Zou, Gen; Qin, Yuqi; Ma, Liang; Li, Jie; Zheng, Huajun; Wang, Shengyue; Wang, Chengshu; Xun, Luying; Zhao, Guo-Ping; Zhou, Zhihua; Qu, Yinbo

    2013-01-01

    Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.

  5. The mitochondrial genome of Dastarcus helophoroides (Coleoptera: Bothrideridae) and related phylogenetic analyses.

    Science.gov (United States)

    Zhang, Zhengqing; Wang, Xiaoji; Li, Rongzhou; Guo, Ruijian; Zhang, Wei; Song, Wang; Hao, Chunfeng; Wang, Huapeng; Li, Menglou

    2015-04-10

    The complete mitochondrial genome of Dastarcus helophoroides (Coleoptera: Bothrideridae) which consists of 13 PCGs, 22 tRNA genes, two rRNA genes and a non-coding region (D-loop), is sequenced for its nucleotide sequence of 15,878 bp (GenBank: KF811054.1). The genome has a typical gene order which is identical to other Coleoptera species. Except for COI gene generally starts with non-canonical initial codon, all protein-coding genes start with ATN codon and terminate with the stop codon TA(A) or TAG. The secondary structure of rrnL and rrnS consists of 48 helices (contains four newly proposed helices) and 35 helices (contains two newly proposed helices) respectively. All 22 tRNAs in D. helophoroides are predicted to fold into typical cloverleaf secondary structure, except trnS1 (AGN), in which the dihydrouracil arm (DHU arm) could not form stable stem-loop structure. Thirteen protein-coding genes (nucleotide dataset and nucleic acid dataset) of the available species (29 taxa) have been used to infer the phylogenetic relationships among these orders. Tenebrionoidea and Cucujoidea form a sister group, and D. helophoroides is classified into Cucujoidea (Bothrideridae). The study first research on the phylogenetic analyses involving to the D. helophoroides mitogenome, and the results strongly bolster the current morphology-based hypothesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Phylogenetic analyses of endoparasitic Acanthocephala based on mitochondrial genomes suggest secondary loss of sensory organs.

    Science.gov (United States)

    Weber, Mathias; Wey-Fabrizius, Alexandra R; Podsiadlowski, Lars; Witek, Alexander; Schill, Ralph O; Sugár, László; Herlyn, Holger; Hankeln, Thomas

    2013-01-01

    The metazoan taxon Syndermata (Monogononta, Bdelloidea, Seisonidea, Acanthocephala) comprises species with vastly different lifestyles. The focus of this study is on the phylogeny within the syndermatan subtaxon Acanthocephala (thorny-headed worms, obligate endoparasites). In order to investigate the controversially discussed phylogenetic relationships of acanthocephalan subtaxa we have sequenced the mitochondrial (mt) genomes of Echinorhynchus truttae (Palaeacanthocephala), Paratenuisentis ambiguus (Eoacanthocephala), Macracanthorhynchus hirudinaceus (Archiacanthocephala), and Philodina citrina (Bdelloidea). In doing so, we present the largest molecular phylogenetic dataset so far for this question comprising all major subgroups of Acanthocephala. Alongside with publicly available mt genome data of four additional syndermatans as well as 18 other lophotrochozoan (spiralian) taxa and one outgroup representative, the derived protein-coding sequences were used for Maximum Likelihood as well as Bayesian phylogenetic analyses. We achieved entirely congruent results, whereupon monophyletic Archiacanthocephala represent the sister taxon of a clade comprising Eoacanthocephala and monophyletic Palaeacanthocephala (Echinorhynchida). This topology suggests the secondary loss of lateral sensory organs (sensory pores) within Palaeacanthocephala and is further in line with the emergence of apical sensory organs in the stem lineage of Archiacanthocephala.

  7. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    Directory of Open Access Journals (Sweden)

    Guodong Liu

    Full Text Available Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.

  8. Estimation of main diversification time-points of hantaviruses using phylogenetic analyses of complete genomes.

    Science.gov (United States)

    Castel, Guillaume; Tordo, Noël; Plyusnin, Alexander

    2017-04-02

    Because of the great variability of their reservoir hosts, hantaviruses are excellent models to evaluate the dynamics of virus-host co-evolution. Intriguing questions remain about the timescale of the diversification events that influenced this evolution. In this paper we attempted to estimate the first ever timing of hantavirus diversification based on thirty five available complete genomes representing five major groups of hantaviruses and the assumption of co-speciation of hantaviruses with their respective mammal hosts. Phylogenetic analyses were used to estimate the main diversification points during hantavirus evolution in mammals while host diversification was mostly estimated from independent calibrators taken from fossil records. Our results support an earlier developed hypothesis of co-speciation of known hantaviruses with their respective mammal hosts and hence a common ancestor for all hantaviruses carried by placental mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Crowdsourcing genomic analyses of ash and ash dieback – power to the people

    Directory of Open Access Journals (Sweden)

    MacLean Dan

    2013-02-01

    Full Text Available Abstract Ash dieback is a devastating fungal disease of ash trees that has swept across Europe and recently reached the UK. This emergent pathogen has received little study in the past and its effect threatens to overwhelm the ash population. In response to this we have produced some initial genomics datasets and taken the unusual step of releasing them to the scientific community for analysis without first performing our own. In this manner we hope to ‘crowdsource’ analyses and bring the expertise of the community to bear on this problem as quickly as possible. Our data has been released through our website at oadb.tsl.ac.uk and a public GitHub repository.

  10. Comparative genomic analyses of the cyanobacterium, Lyngbya aestuarii BL J, a powerful hydrogen producer.

    Directory of Open Access Journals (Sweden)

    Ankita eKothari

    2013-12-01

    Full Text Available The filamentous, non-heterocystous cyanobacterium Lyngbya aestuarii is an important contributor to marine intertidal microbial mats system worldwide. The recent isolate L. aestuarii BL J, is an unusually powerful hydrogen producer. Here we report a morphological, ultrastructural and genomic characterization of this strain to set the basis for future systems studies and applications of this organism. The filaments contain circa 17 μm wide trichomes, composed of stacked disk-like short cells (2 μm long, encased in a prominent, laminated exopolysaccharide sheath. Cellular division occurs by transversal centripetal growth of cross-walls, where several rounds of division proceed simultaneously. Filament division occurs by cell self-immolation of one or groups of cells (necridial cells at the breakage point. Short, sheath-less, motile filaments (hormogonia are also formed. Morphologically and phylogenetically L. aestuarii belongs to a clade of important cyanobacteria that include members of the marine Trichodesmiun and Hydrocoleum genera, as well as terrestrial Microcoleus vaginatus strains, and alkalyphilic strains of Arthrospira. A draft genome of strain BL J was compared to those of other cyanobacteria in order to ascertain some of its ecological constraints and biotechnological potential. The genome had an average GC content of 41.1 %. Of the 6.87 Mb sequenced, 6.44 Mb was present as large contigs (>10,000 bp. It contained 6515 putative protein-encoding genes, of which, 43 % encode proteins of known functional role, 26 % corresponded to proteins with domain or family assignments, 19.6 % encode conserved hypothetical proteins, and 11.3 % encode apparently unique hypothetical proteins. The strain’s genome reveals its adaptations to a life of exposure to intense solar radiation and desiccation. It likely employs the storage compounds, glycogen and cyanophycin but no polyhydroxyalkanoates, and can produce the osmolytes, trehalose and glycine

  11. Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing.

    Science.gov (United States)

    Wiszniewska, Joanna; Bi, Weimin; Shaw, Chad; Stankiewicz, Pawel; Kang, Sung-Hae L; Pursley, Amber N; Lalani, Seema; Hixson, Patricia; Gambin, Tomasz; Tsai, Chun-hui; Bock, Hans-Georg; Descartes, Maria; Probst, Frank J; Scaglia, Fernando; Beaudet, Arthur L; Lupski, James R; Eng, Christine; Cheung, Sau Wai; Bacino, Carlos; Patel, Ankita

    2014-01-01

    In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60,000 SNP probes, referred to as Chromosomal Microarray Analysis - Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner.

  12. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

    Directory of Open Access Journals (Sweden)

    Ryan Joseph F

    2011-01-01

    Full Text Available Abstract Background Mutations in the Otopetrin 1 gene (Otop1 in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH subtype 1G (Ush1g, both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF, a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq data in mouse and human embryonic stem (ES cells combined with detection of CTCF-binding motifs. Conclusions The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s of Ush1g and Otop in developmental pathways.

  13. Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

    Science.gov (United States)

    Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

  14. Genome Sequence of Azospirillum brasilense CBG497 and Comparative Analyses of Azospirillum Core and Accessory Genomes provide Insight into Niche Adaptation

    Directory of Open Access Journals (Sweden)

    Victor González

    2012-09-01

    Full Text Available Bacteria of the genus Azospirillum colonize roots of important cereals and grasses, and promote plant growth by several mechanisms, notably phytohormone synthesis. The genomes of several Azospirillum strains belonging to different species, isolated from various host plants and locations, were recently sequenced and published. In this study, an additional genome of an A. brasilense strain, isolated from maize grown on an alkaline soil in the northeast of Mexico, strain CBG497, was obtained. Comparative genomic analyses were performed on this new genome and three other genomes (A. brasilense Sp245, A. lipoferum 4B and Azospirillum sp. B510. The Azospirillum core genome was established and consists of 2,328 proteins, representing between 30% to 38% of the total encoded proteins within a genome. It is mainly chromosomally-encoded and contains 74% of genes of ancestral origin shared with some aquatic relatives. The non-ancestral part of the core genome is enriched in genes involved in signal transduction, in transport and in metabolism of carbohydrates and amino-acids, and in surface properties features linked to adaptation in fluctuating environments, such as soil and rhizosphere. Many genes involved in colonization of plant roots, plant-growth promotion (such as those involved in phytohormone biosynthesis, and properties involved in rhizosphere adaptation (such as catabolism of phenolic compounds, uptake of iron are restricted to a particular strain and/or species, strongly suggesting niche-specific adaptation.

  15. Genome Sequence of Azospirillum brasilense CBG497 and Comparative Analyses of Azospirillum Core and Accessory Genomes provide Insight into Niche Adaptation

    Science.gov (United States)

    Wisniewski-Dyé, Florence; Lozano, Luis; Acosta-Cruz, Erika; Borland, Stéphanie; Drogue, Benoît; Prigent-Combaret, Claire; Rouy, Zoé; Barbe, Valérie; Mendoza Herrera, Alberto; González, Victor; Mavingui, Patrick

    2012-01-01

    Bacteria of the genus Azospirillum colonize roots of important cereals and grasses, and promote plant growth by several mechanisms, notably phytohormone synthesis. The genomes of several Azospirillum strains belonging to different species, isolated from various host plants and locations, were recently sequenced and published. In this study, an additional genome of an A. brasilense strain, isolated from maize grown on an alkaline soil in the northeast of Mexico, strain CBG497, was obtained. Comparative genomic analyses were performed on this new genome and three other genomes (A. brasilense Sp245, A. lipoferum 4B and Azospirillum sp. B510). The Azospirillum core genome was established and consists of 2,328 proteins, representing between 30% to 38% of the total encoded proteins within a genome. It is mainly chromosomally-encoded and contains 74% of genes of ancestral origin shared with some aquatic relatives. The non-ancestral part of the core genome is enriched in genes involved in signal transduction, in transport and in metabolism of carbohydrates and amino-acids, and in surface properties features linked to adaptation in fluctuating environments, such as soil and rhizosphere. Many genes involved in colonization of plant roots, plant-growth promotion (such as those involved in phytohormone biosynthesis), and properties involved in rhizosphere adaptation (such as catabolism of phenolic compounds, uptake of iron) are restricted to a particular strain and/or species, strongly suggesting niche-specific adaptation. PMID:24705077

  16. Pan-genome analyses identify lineage- and niche-specific markers of evolution and adaptation in Epsilonproteobacteria

    Directory of Open Access Journals (Sweden)

    Ying eZhang

    2014-03-01

    Full Text Available The rapidly increasing availability of complete bacterial genomes has created new opportunities for reconstructing bacterial evolution, but it has also highlighted the difficulty to fully understand the genomic and functional variations occurring among different lineages. Using the class Epsilonproteobacteria as a case study, we investigated the composition, flexibility, and function of its pan-genomes. Models were constructed to extrapolate the expansion of pan-genomes at three different taxonomic levels. The results show that, for Epsilonproteobacteria the seemingly large genome variations among strains of the same species are less noticeable when compared with groups at higher taxonomic ranks, indicating that genome stability is imposed by the potential existence of taxonomic boundaries. The analyses of pan-genomes has also defined a set of universally conserved core genes, based on which a phylogenetic tree was constructed to confirm that thermophilic species from deep-sea hydrothermal vents represent the most ancient lineages of Epsilonproteobacteria. Moreover, by comparing the flexible genome of a chemoautotrophic deep-sea vent species to 1 genomes of species belonging to the same genus, but inhabiting different environments, and 2 genomes of other vent species, but belonging to different genera, we were able to delineate the relative importance of lineage-specific versus niche-specific genes. This result not only emphasizes the overall importance of phylogenetic proximity in shaping the variable part of the genome, but also highlights the adaptive functions of niche-specific genes. Overall, by modeling the expansion of pan-genomes and analyzing core and flexible genes, this study provides snapshots on how the complex processes of gene acquisition, conservation, and removal affect the evolution of different species, and contribute to the metabolic diversity and versatility of Epsilonproteobacteria.

  17. No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

    Directory of Open Access Journals (Sweden)

    Jens Baumert

    Full Text Available Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI. Genome-wide association studies (GWAS have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

  18. Genome analyses of an aggressive and invasive lineage of the Irish potato famine pathogen.

    Directory of Open Access Journals (Sweden)

    David E L Cooke

    Full Text Available Pest and pathogen losses jeopardise global food security and ever since the 19(th century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemics.

  19. Genome Analyses of an Aggressive and Invasive Lineage of the Irish Potato Famine Pathogen

    Science.gov (United States)

    Raffaele, Sylvain; Bain, Ruairidh A.; Cooke, Louise R.; Etherington, Graham J.; Deahl, Kenneth L.; Farrer, Rhys A.; Gilroy, Eleanor M.; Goss, Erica M.; Grünwald, Niklaus J.; Hein, Ingo; MacLean, Daniel; McNicol, James W.; Randall, Eva; Oliva, Ricardo F.; Pel, Mathieu A.; Shaw, David S.; Squires, Julie N.; Taylor, Moray C.; Vleeshouwers, Vivianne G. A. A.; Birch, Paul R. J.; Lees, Alison K.; Kamoun, Sophien

    2012-01-01

    Pest and pathogen losses jeopardise global food security and ever since the 19th century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemics. PMID:23055926

  20. Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments.

    Science.gov (United States)

    Noto, Jennifer M; Chopra, Abha; Loh, John T; Romero-Gallo, Judith; Piazuelo, M Blanca; Watson, Mark; Leary, Shay; Beckett, Amber C; Wilson, Keith T; Cover, Timothy L; Mallal, Simon; Israel, Dawn A; Peek, Richard M

    2017-09-18

    Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease. Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed. A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034). These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Comparison of analyses of the XVth QTLMAS common dataset III: Genomic Estimations of Breeding Values

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    Demeure Olivier

    2012-05-01

    Full Text Available Abstract Background The QTLMAS XVth dataset consisted of pedigree, marker genotypes and quantitative trait performances of animals with a sib family structure. Pedigree and genotypes concerned 3,000 progenies among those 2,000 were phenotyped. The trait was regulated by 8 QTLs which displayed additive, imprinting or epistatic effects. The 1,000 unphenotyped progenies were considered as candidates to selection and their Genomic Estimated Breeding Values (GEBV were evaluated by participants of the XVth QTLMAS workshop. This paper aims at comparing the GEBV estimation results obtained by seven participants to the workshop. Methods From the known QTL genotypes of each candidate, two "true" genomic values (TV were estimated by organizers: the genotypic value of the candidate (TGV and the expectation of its progeny genotypic values (TBV. GEBV were computed by the participants following different statistical methods: random linear models (including BLUP and Ridge Regression, selection variable techniques (LASSO, Elastic Net and Bayesian methods. Accuracy was evaluated by the correlation between TV (TGV or TBV and GEBV presented by participants. Rank correlation of the best 10% of individuals and error in predictions were also evaluated. Bias was tested by regression of TV on GEBV. Results Large differences between methods were found for all criteria and type of genetic values (TGV, TBV. In general, the criteria ranked consistently methods belonging to the same family. Conclusions Bayesian methods - A

  2. Genetic Diversity of Marine Anaerobic Ammonium-Oxidizing Bacteria as Revealed by Genomic and Proteomic Analyses of 'Candidatus Scalindua japonica'.

    Science.gov (United States)

    Oshiki, Mamoru; Mizuto, Keisuke; Kimura, Zenichiro; Kindaichi, Tomonori; Satoh, Hisashi; Okabe, Satoshi

    2017-09-11

    Anaerobic ammonium-oxidizing (anammox) bacteria affiliated with the genus 'Candidatus Scalindua' are responsible for significant nitrogen loss in oceans, and thus their ecophysiology is of great interest. Here, we enriched a marine anammox bacterium, 'Ca. S. japonica' from a Hiroshima bay sediment in Japan, and comparative genomic and proteomic analyses of 'Ca. S. japonica' were conducted. Sequence of the 4.81-Mb genome containing 4,019 coding regions of genes (CDSs) composed of 47 contigs was determined. In the proteome, 1,762 out of 4,019 CDSs in the 'Ca. S. japonica' genome were detected. Based on the genomic and proteomic data, the core anammox process and carbon fixation of 'Ca. S. japonica' were further investigated. Additionally, the present study provides the first detailed insights into the genetic background responsible for iron acquisition and menaquinone biosynthesis in anammox bacterial cells. Comparative analysis of the 'Ca. Scalindua' genomes revealed that the 1,502 genes found in the 'Ca. S. japonica' genome were not present in the 'Ca. S. profunda' and 'Ca. S. rubra' genomes, showing a high genomic diversity. This result may reflect a high phylogenetic diversity of the genus 'Ca. Scalindua'. This article is protected by copyright. All rights reserved. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

    NARCIS (Netherlands)

    Direk, Nese; Williams, Stephanie; Smith, Jennifer A.; Ripke, Stephan; Air, Tracy; Amare, Azmeraw T.; Amin, Najaf; Baune, Bernhard T.; Bennett, David A.; Blackwood, Douglas H. R.; Boomsma, Dorret; Breen, Gerome; Buttenschon, Henriette N.; Byrne, Enda M.; Borglum, Anders D.; Castelao, Enrique; Cichon, Sven; Clarke, Toni-Kim; Cornelis, Marilyn C.; Dannlowski, Udo; De Jager, Philip L.; Demirkan, Ayse; Domenici, Enrico; van Duijn, Cornelia M.; Dunn, Erin C.; Eriksson, Johan G.; Esko, Tonu; Faul, Jessica D.; Ferrucci, Luigi; Fornage, Myriam; de Geus, Eco; Gill, Michael; Gordon, Scott D.; Grabe, Hans Joergen; van Grootheest, Gerard; Hamilton, Steven P.; Hartman, Catharina A.; Heath, Andrew C.; Hek, Karin; Hofman, Albert; Homuth, Georg; Horn, Carsten; Hottenga, Jouke Jan; Kardia, Sharon L. R.; Kloiber, Stefan; Koenen, Karestan; Kutalik, Zoltan; Ladwig, Karl-Heinz; Lahti, Jari; Levinson, Douglas F.; Lewis, Cathryn M.; Lewis, Glyn; Li, Qingqin S.; Llewellyn, David J.; Lucae, Susanne; Lunetta, Kathryn L.; MacIntyre, Donald J.; Madden, Pamela; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Milaneschi, Yuri; Montgomery, Grant W.; Mors, Ole; Mosley, Thomas H.; Murabito, Joanne M.; Mueller-Myhsok, Bertram; Nothen, Markus M.; Nyholt, Dale R.; O'Donovan, Michael C.; Penninx, Brenda W.; Pergadia, Michele L.; Perlis, Roy; Potash, James B.; Preisig, Martin; Purcell, Shaun M.; Quiroz, Jorge A.; Raikkonen, Katri; Rice, John P.; Rietschel, Marcella; Rivera, Margarita; Schulze, Thomas G.; Shi, Jianxin; Shyn, Stanley; Sinnamon, Grant C.; Smit, Johannes H.; Smoller, Jordan W.; Snieder, Harold; Tanaka, Toshiko; Tansey, Katherine E.; Teumer, Alexander; Uher, Rudolf; Umbricht, Daniel; Van der Auwera, Sandra; Ware, Erin B.; Weir, David R.; Weissman, Myrna M.; Willemsen, Gonneke; Yang, Jingyun; Zhao, Wei; Tiemeier, Henning; Sullivan, Patrick F.

    2017-01-01

    BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide

  4. Analyses of genome architecture and gene expression reveal novel candidate virulence factors in the secretome of Phytophthora infestans

    Directory of Open Access Journals (Sweden)

    Cano Liliana M

    2010-11-01

    Full Text Available Abstract Background Phytophthora infestans is the most devastating pathogen of potato and a model organism for the oomycetes. It exhibits high evolutionary potential and rapidly adapts to host plants. The P. infestans genome experienced a repeat-driven expansion relative to the genomes of Phytophthora sojae and Phytophthora ramorum and shows a discontinuous distribution of gene density. Effector genes, such as members of the RXLR and Crinkler (CRN families, localize to expanded, repeat-rich and gene-sparse regions of the genome. This distinct genomic environment is thought to contribute to genome plasticity and host adaptation. Results We used in silico approaches to predict and describe the repertoire of P. infestans secreted proteins (the secretome. We defined the "plastic secretome" as a subset of the genome that (i encodes predicted secreted proteins, (ii is excluded from genome segments orthologous to the P. sojae and P. ramorum genomes and (iii is encoded by genes residing in gene sparse regions of P. infestans genome. Although including only ~3% of P. infestans genes, the plastic secretome contains ~62% of known effector genes and shows >2 fold enrichment in genes induced in planta. We highlight 19 plastic secretome genes induced in planta but distinct from previously described effectors. This list includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine-rich proteins and repeat containing proteins that we propose to be novel candidate virulence factors. Conclusions This work revealed a remarkably diverse plastic secretome. It illustrates the value of combining genome architecture with comparative genomics to identify novel candidate virulence factors from pathogen genomes.

  5. The complete chloroplast genome sequences of five Epimedium species: lights into phylogenetic and taxonomic analyses

    Directory of Open Access Journals (Sweden)

    Yanjun eZhang

    2016-03-01

    Full Text Available Epimedium L. is a phylogenetically and economically important genus in the family Berberidaceae. We here sequenced the complete chloroplast (cp genomes of four Epimedium species using Illumina sequencing technology via a combination of de novo and reference-guided assembly, which was also the first comprehensive cp genome analysis on Epimedium combining the cp genome sequence of E. koreanum previously reported. The five Epimedium cp genomes exhibited typical quadripartite and circular structure that was rather conserved in genomic structure and the synteny of gene order. However, these cp genomes presented obvious variations at the boundaries of the four regions because of the expansion and contraction of the inverted repeat (IR region and the single-copy (SC boundary regions. The trnQ-UUG duplication occurred in the five Epimedium cp genomes, which was not found in the other basal eudicotyledons. The rapidly evolving cp genome regions were detected among the five cp genomes, as well as the difference of simple sequence repeats (SSR and repeat sequence were identified. Phylogenetic relationships among the five Epimedium species based on their cp genomes showed accordance with the updated system of the genus on the whole, but reminded that the evolutionary relationships and the divisions of the genus need further investigation applying more evidences. The availability of these cp genomes provided valuable genetic information for accurately identifying species, taxonomy and phylogenetic resolution and evolution of Epimedium, and assist in exploration and utilization of Epimedium plants.

  6. Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2009-02-01

    Full Text Available Abstract Background Nickel (Ni and cobalt (Co are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i transport systems, and (ii metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO is the most common prokaryotic Ni/Co transporter, while Ni-dependent urease and Ni-Fe hydrogenase, and B12-dependent methionine synthase (MetH, ribonucleotide reductase and methylmalonyl-CoA mutase are the most widespread metalloproteins for Ni and Co, respectively. Occurrence of other metalloenzymes showed a mosaic distribution and a new B12-dependent protein family was predicted. Deltaproteobacteria and Methanosarcina generally have larger Ni- and Co-dependent proteomes. On the other hand, utilization of these two metals is limited in eukaryotes, and very few of these organisms utilize both of them. The Ni-utilizing eukaryotes are mostly fungi (except saccharomycotina and plants, whereas most B12-utilizing organisms are animals. The NiCoT transporter family is the most widespread eukaryotic Ni transporter, and eukaryotic urease and MetH are the most common Ni- and B12-dependent enzymes, respectively. Finally, investigation of environmental and other conditions and identity of organisms that show dependence on Ni or Co revealed that host-associated organisms (particularly obligate intracellular parasites and endosymbionts have a tendency for loss of Ni/Co utilization. Conclusion Our data provide information on the evolutionary dynamics of Ni and Co utilization and highlight widespread use of these metals in the three

  7. Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population

    Science.gov (United States)

    Park, Hansoo; Lee, Seungbok; Kim, Hyun-Jin; Ju, Young Seok; Shin, Jong-Yeon; Hong, Dongwan; von Grotthuss, Marcin; Lee, Dong-Sung; Park, Changho; Kim, Jennifer Hayeon; Kim, Boram; Yoo, Yun Joo; Cho, Sung-Il; Sung, Joohon; Lee, Charles; Kim, Jong-Il; Seo, Jeong-Sun

    2012-01-01

    Background Musical abilities such as recognising music and singing performance serve as means for communication and are instruments in sexual selection. Specific regions of the brain have been found to be activated by musical stimuli, but these have rarely been extended to the discovery of genes and molecules associated with musical ability. Methods A total of 1008 individuals from 73 families were enrolled and a pitch-production accuracy test was applied to determine musical ability. To identify genetic loci and variants that contribute to musical ability, we conducted family-based linkage and association analyses, and incorporated the results with data from exome sequencing and array comparative genomic hybridisation analyses. Results We found significant evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose supporting interval overlaps a previous study in Finnish families, and identified an intergenic single nucleotide polymorphism (SNP) (rs1251078, p=8.4×10−17) near UGT8, a gene highly expressed in the central nervous system and known to act in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to be highly associated with musical ability (rs4148254, p=8.0×10−17), and a 6.2 kb copy number loss near UGT8 showed a plausible association with musical ability (p=2.9×10−6). Conclusions This study provides new insight into the genetics of musical ability, exemplifying a methodology to assign functional significance to synonymous and non-coding alleles by integrating multiple experimental methods. PMID:23118445

  8. Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization

    Science.gov (United States)

    Zhang, Yan; Rodionov, Dmitry A; Gelfand, Mikhail S; Gladyshev, Vadim N

    2009-01-01

    Background Nickel (Ni) and cobalt (Co) are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i) transport systems, and (ii) metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO is the most common prokaryotic Ni/Co transporter, while Ni-dependent urease and Ni-Fe hydrogenase, and B12-dependent methionine synthase (MetH), ribonucleotide reductase and methylmalonyl-CoA mutase are the most widespread metalloproteins for Ni and Co, respectively. Occurrence of other metalloenzymes showed a mosaic distribution and a new B12-dependent protein family was predicted. Deltaproteobacteria and Methanosarcina generally have larger Ni- and Co-dependent proteomes. On the other hand, utilization of these two metals is limited in eukaryotes, and very few of these organisms utilize both of them. The Ni-utilizing eukaryotes are mostly fungi (except saccharomycotina) and plants, whereas most B12-utilizing organisms are animals. The NiCoT transporter family is the most widespread eukaryotic Ni transporter, and eukaryotic urease and MetH are the most common Ni- and B12-dependent enzymes, respectively. Finally, investigation of environmental and other conditions and identity of organisms that show dependence on Ni or Co revealed that host-associated organisms (particularly obligate intracellular parasites and endosymbionts) have a tendency for loss of Ni/Co utilization. Conclusion Our data provide information on the evolutionary dynamics of Ni and Co utilization and highlight widespread use of these metals in the three domains of life, yet only a

  9. Genome based analyses of six hexacorallian species reject the “naked coral” hypothesis

    KAUST Repository

    Wang, Xin

    2017-09-23

    Scleractinian corals are the foundation species of the coral-reef ecosystem. Their calcium carbonate skeletons form extensive structures that are home to millions of species, making coral reefs one of the most diverse ecosystems of our planet. However, our understanding of how reef-building corals have evolved the ability to calcify and become the ecosystem builders they are today is hampered by uncertain relationships within their subclass Hexacorallia. Corallimorpharians have been proposed to originate from a complex scleractinian ancestor that lost the ability to calcify in response to increasing ocean acidification, suggesting the possibility for corals to lose and gain the ability to calcify in response to increasing ocean acidification. Here we employed a phylogenomic approach using whole-genome data from six hexacorallian species to resolve the evolutionary relationship between reef-building corals and their non-calcifying relatives. Phylogenetic analysis based on 1,421 single-copy orthologs, as well as gene presence/absence and synteny information, converged on the same topologies, showing strong support for scleractinian monophyly and a corallimorpharian sister clade. Our broad phylogenomic approach using sequence-based and sequence-independent analyses provides unambiguous evidence for the monophyly of scleractinian corals and the rejection of corallimorpharians as descendants of a complex coral ancestor.

  10. Genome-Wide Analyses of Individual Strongyloides stercoralis (Nematoda: Rhabditoidea) Provide Insights into Population Structure and Reproductive Life Cycles

    Science.gov (United States)

    Aung, Myo Pa Pa Thet Hnin Htwe; Afrin, Tanzila; Nagayasu, Eiji; Tanaka, Ryusei; Higashiarakawa, Miwa; Win, Kyu Kyu; Hirata, Tetsuo; Htike, Wah Win; Fujita, Jiro; Maruyama, Haruhiko

    2016-01-01

    The helminth Strongyloides stercoralis, which is transmitted through soil, infects 30–100 million people worldwide. S. stercoralis reproduces sexually outside the host as well as asexually within the host, which causes a life-long infection. To understand the population structure and transmission patterns of this parasite, we re-sequenced the genomes of 33 individual S. stercoralis nematodes collected in Myanmar (prevalent region) and Japan (non-prevalent region). We utilised a method combining whole genome amplification and next-generation sequencing techniques to detect 298,202 variant positions (0.6% of the genome) compared with the reference genome. Phylogenetic analyses of SNP data revealed an unambiguous geographical separation and sub-populations that correlated with the host geographical origin, particularly for the Myanmar samples. The relatively higher heterozygosity in the genomes of the Japanese samples can possibly be explained by the independent evolution of two haplotypes of diploid genomes through asexual reproduction during the auto-infection cycle, suggesting that analysing heterozygosity is useful and necessary to infer infection history and geographical prevalence. PMID:28033376

  11. Hybridization Capture Using RAD Probes (hyRAD, a New Tool for Performing Genomic Analyses on Collection Specimens.

    Directory of Open Access Journals (Sweden)

    Tomasz Suchan

    Full Text Available In the recent years, many protocols aimed at reproducibly sequencing reduced-genome subsets in non-model organisms have been published. Among them, RAD-sequencing is one of the most widely used. It relies on digesting DNA with specific restriction enzymes and performing size selection on the resulting fragments. Despite its acknowledged utility, this method is of limited use with degraded DNA samples, such as those isolated from museum specimens, as these samples are less likely to harbor fragments long enough to comprise two restriction sites making possible ligation of the adapter sequences (in the case of double-digest RAD or performing size selection of the resulting fragments (in the case of single-digest RAD. Here, we address these limitations by presenting a novel method called hybridization RAD (hyRAD. In this approach, biotinylated RAD fragments, covering a random fraction of the genome, are used as baits for capturing homologous fragments from genomic shotgun sequencing libraries. This simple and cost-effective approach allows sequencing of orthologous loci even from highly degraded DNA samples, opening new avenues of research in the field of museum genomics. Not relying on the restriction site presence, it improves among-sample loci coverage. In a trial study, hyRAD allowed us to obtain a large set of orthologous loci from fresh and museum samples from a non-model butterfly species, with a high proportion of single nucleotide polymorphisms present in all eight analyzed specimens, including 58-year-old museum samples. The utility of the method was further validated using 49 museum and fresh samples of a Palearctic grasshopper species for which the spatial genetic structure was previously assessed using mtDNA amplicons. The application of the method is eventually discussed in a wider context. As it does not rely on the restriction site presence, it is therefore not sensitive to among-sample loci polymorphisms in the restriction sites

  12. Genomic Resources for Water Yam (Dioscorea alata L.): Analyses of EST-Sequences, De Novo Sequencing and GBS Libraries.

    Science.gov (United States)

    Saski, Christopher A; Bhattacharjee, Ranjana; Scheffler, Brian E; Asiedu, Robert

    2015-01-01

    The reducing cost and rapid progress in next-generation sequencing techniques coupled with high performance computational approaches have resulted in large-scale discovery of advanced genomic resources in several model and non-model plant species. Yam (Dioscorea spp.) is a major food and cash crop in many countries but research efforts have been limited to understand the genetics and generate genomic information for the crop. The availability of a large number of genomic resources including genome-wide molecular markers will accelerate the breeding efforts and application of genomic selection in yams. In the present study, several methods including expressed sequence tags (EST)-sequencing, de novo sequencing, and genotyping-by-sequencing (GBS) profiles on two yam (Dioscorea alata L.) genotypes (TDa 95/00328 and TDa 95-310) was performed to generate genomic resources for use in its improvement programs. This includes a comprehensive set of EST-SSRs, genomic SSRs, whole genome SNPs, and reduced representation SNPs. A total of 1,152 EST-SSRs were developed from >40,000 EST-sequences generated from the two genotypes. A set of 388 EST-SSRs were validated as polymorphic showing a polymorphism rate of 34% when tested on two diverse parents targeted for anthracnose disease. In addition, approximately 40X de novo whole genome sequence coverage was generated for each of the two genotypes, and a total of 18,584 and 15,952 genomic SSRs were identified for TDa 95/00328 and TDa 95-310, respectively. A custom made pipeline resulted in the selection of 573 genomic SSRs common across the two genotypes, of which only eight failed, 478 being polymorphic and 62 monomorphic indicating a polymorphic rate of 83.5%. Additionally, 288,505 high quality SNPs were also identified between these two genotypes. Genotyping by sequencing reads on these two genotypes also revealed 36,790 overlapping SNP positions that are distributed throughout the genome. Our efforts in using different approaches

  13. Genomic Resources for Water Yam (Dioscorea alata L.: Analyses of EST-Sequences, De Novo Sequencing and GBS Libraries.

    Directory of Open Access Journals (Sweden)

    Christopher A Saski

    Full Text Available The reducing cost and rapid progress in next-generation sequencing techniques coupled with high performance computational approaches have resulted in large-scale discovery of advanced genomic resources in several model and non-model plant species. Yam (Dioscorea spp. is a major food and cash crop in many countries but research efforts have been limited to understand the genetics and generate genomic information for the crop. The availability of a large number of genomic resources including genome-wide molecular markers will accelerate the breeding efforts and application of genomic selection in yams. In the present study, several methods including expressed sequence tags (EST-sequencing, de novo sequencing, and genotyping-by-sequencing (GBS profiles on two yam (Dioscorea alata L. genotypes (TDa 95/00328 and TDa 95-310 was performed to generate genomic resources for use in its improvement programs. This includes a comprehensive set of EST-SSRs, genomic SSRs, whole genome SNPs, and reduced representation SNPs. A total of 1,152 EST-SSRs were developed from >40,000 EST-sequences generated from the two genotypes. A set of 388 EST-SSRs were validated as polymorphic showing a polymorphism rate of 34% when tested on two diverse parents targeted for anthracnose disease. In addition, approximately 40X de novo whole genome sequence coverage was generated for each of the two genotypes, and a total of 18,584 and 15,952 genomic SSRs were identified for TDa 95/00328 and TDa 95-310, respectively. A custom made pipeline resulted in the selection of 573 genomic SSRs common across the two genotypes, of which only eight failed, 478 being polymorphic and 62 monomorphic indicating a polymorphic rate of 83.5%. Additionally, 288,505 high quality SNPs were also identified between these two genotypes. Genotyping by sequencing reads on these two genotypes also revealed 36,790 overlapping SNP positions that are distributed throughout the genome. Our efforts in using

  14. Comparative Genomics Including the Early-Diverging Smut Fungus Ceraceosorus bombacis Reveals Signatures of Parallel Evolution within Plant and Animal Pathogens of Fungi and Oomycetes.

    Science.gov (United States)

    Sharma, Rahul; Xia, Xiaojuan; Riess, Kai; Bauer, Robert; Thines, Marco

    2015-08-27

    Ceraceosorus bombacis is an early-diverging lineage of smut fungi and a pathogen of cotton trees (Bombax ceiba). To study the evolutionary genomics of smut fungi in comparison with other fungal and oomycete pathogens, the genome of C. bombacis was sequenced and comparative genomic analyses were performed. The genome of 26.09 Mb encodes for 8,024 proteins, of which 576 are putative-secreted effector proteins (PSEPs). Orthology analysis revealed 30 ortholog PSEPs among six Ustilaginomycotina genomes, the largest groups of which are lytic enzymes, such as aspartic peptidase and glycoside hydrolase. Positive selection analyses revealed the highest percentage of positively selected PSEPs in C. bombacis compared with other Ustilaginomycotina genomes. Metabolic pathway analyses revealed the absence of genes encoding for nitrite and nitrate reductase in the genome of the human skin pathogen Malassezia globosa, but these enzymes are present in the sequenced plant pathogens in smut fungi. Interestingly, these genes are also absent in cultivable oomycete animal pathogens, while nitrate reductase has been lost in cultivable oomycete plant pathogens. Similar patterns were also observed for obligate biotrophic and hemi-biotrophic fungal and oomycete pathogens. Furthermore, it was found that both fungal and oomycete animal pathogen genomes are lacking cutinases and pectinesterases. Overall, these findings highlight the parallel evolution of certain genomic traits, revealing potential common evolutionary trajectories among fungal and oomycete pathogens, shaping the pathogen genomes according to their lifestyle.

  15. Weighted Statistical Binning: Enabling Statistically Consistent Genome-Scale Phylogenetic Analyses

    Science.gov (United States)

    Bayzid, Md Shamsuzzoha; Mirarab, Siavash; Boussau, Bastien; Warnow, Tandy

    2015-01-01

    Because biological processes can result in different loci having different evolutionary histories, species tree estimation requires multiple loci from across multiple genomes. While many processes can result in discord between gene trees and species trees, incomplete lineage sorting (ILS), modeled by the multi-species coalescent, is considered to be a dominant cause for gene tree heterogeneity. Coalescent-based methods have been developed to estimate species trees, many of which operate by combining estimated gene trees, and so are called "summary methods". Because summary methods are generally fast (and much faster than more complicated coalescent-based methods that co-estimate gene trees and species trees), they have become very popular techniques for estimating species trees from multiple loci. However, recent studies have established that summary methods can have reduced accuracy in the presence of gene tree estimation error, and also that many biological datasets have substantial gene tree estimation error, so that summary methods may not be highly accurate in biologically realistic conditions. Mirarab et al. (Science 2014) presented the "statistical binning" technique to improve gene tree estimation in multi-locus analyses, and showed that it improved the accuracy of MP-EST, one of the most popular coalescent-based summary methods. Statistical binning, which uses a simple heuristic to evaluate "combinability" and then uses the larger sets of genes to re-calculate gene trees, has good empirical performance, but using statistical binning within a phylogenomic pipeline does not have the desirable property of being statistically consistent. We show that weighting the re-calculated gene trees by the bin sizes makes statistical binning statistically consistent under the multispecies coalescent, and maintains the good empirical performance. Thus, "weighted statistical binning" enables highly accurate genome-scale species tree estimation, and is also statistically

  16. Weighted Statistical Binning: Enabling Statistically Consistent Genome-Scale Phylogenetic Analyses.

    Directory of Open Access Journals (Sweden)

    Md Shamsuzzoha Bayzid

    Full Text Available Because biological processes can result in different loci having different evolutionary histories, species tree estimation requires multiple loci from across multiple genomes. While many processes can result in discord between gene trees and species trees, incomplete lineage sorting (ILS, modeled by the multi-species coalescent, is considered to be a dominant cause for gene tree heterogeneity. Coalescent-based methods have been developed to estimate species trees, many of which operate by combining estimated gene trees, and so are called "summary methods". Because summary methods are generally fast (and much faster than more complicated coalescent-based methods that co-estimate gene trees and species trees, they have become very popular techniques for estimating species trees from multiple loci. However, recent studies have established that summary methods can have reduced accuracy in the presence of gene tree estimation error, and also that many biological datasets have substantial gene tree estimation error, so that summary methods may not be highly accurate in biologically realistic conditions. Mirarab et al. (Science 2014 presented the "statistical binning" technique to improve gene tree estimation in multi-locus analyses, and showed that it improved the accuracy of MP-EST, one of the most popular coalescent-based summary methods. Statistical binning, which uses a simple heuristic to evaluate "combinability" and then uses the larger sets of genes to re-calculate gene trees, has good empirical performance, but using statistical binning within a phylogenomic pipeline does not have the desirable property of being statistically consistent. We show that weighting the re-calculated gene trees by the bin sizes makes statistical binning statistically consistent under the multispecies coalescent, and maintains the good empirical performance. Thus, "weighted statistical binning" enables highly accurate genome-scale species tree estimation, and is also

  17. Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris

    OpenAIRE

    Qian, Wei; Jia, Yantao; Ren, Shuang-Xi; He, Yong-Qiang; Feng, Jia-Xun; Lu, Ling-Feng; Sun, Qihong; Ying, Ge; Tang, Dong-Jie; Tang, Hua; Wu, Wei; Hao, Pei; Wang, Lifeng; Jiang, Bo-Le; Zeng, Shenyan

    2005-01-01

    Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis bet...

  18. Genome-wide divergence and linkage disequilibrium analyses for Capsicum baccatum revealed by genome-anchored single nucleotide polymorphisms

    Science.gov (United States)

    Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to show the distribution of these 2 important incompatible cultivated pepper species. Estimated mean nucleotide...

  19. Hands-on workshops as an effective means of learning advanced technologies including genomics, proteomics and bioinformatics.

    Science.gov (United States)

    Reisdorph, Nichole; Stearman, Robert; Kechris, Katerina; Phang, Tzu Lip; Reisdorph, Richard; Prenni, Jessica; Erle, David J; Coldren, Christopher; Schey, Kevin; Nesvizhskii, Alexey; Geraci, Mark

    2013-12-01

    Genomics and proteomics have emerged as key technologies in biomedical research, resulting in a surge of interest in training by investigators keen to incorporate these technologies into their research. At least two types of training can be envisioned in order to produce meaningful results, quality publications and successful grant applications: (1) immediate short-term training workshops and (2) long-term graduate education or visiting scientist programs. We aimed to fill the former need by providing a comprehensive hands-on training course in genomics, proteomics and informatics in a coherent, experimentally-based framework. This was accomplished through a National Heart, Lung, and Blood Institute (NHLBI)-sponsored 10-day Genomics and Proteomics Hands-on Workshop held at National Jewish Health (NJH) and the University of Colorado School of Medicine (UCD). The course content included comprehensive lectures and laboratories in mass spectrometry and genomics technologies, extensive hands-on experience with instrumentation and software, video demonstrations, optional workshops, online sessions, invited keynote speakers, and local and national guest faculty. Here we describe the detailed curriculum and present the results of short- and long-term evaluations from course attendees. Our educational program consistently received positive reviews from participants and had a substantial impact on grant writing and review, manuscript submissions and publications.

  20. Genomic and transcriptomic analyses of the tangerine pathotype of Alternaria alternata in response to oxidative stress

    Science.gov (United States)

    Wang, Mingshuang; Sun, Xuepeng; Yu, Dongliang; Xu, Jianping; Chung, Kuangren; Li, Hongye

    2016-01-01

    The tangerine pathotype of Alternaria alternata produces the A. citri toxin (ACT) and is the causal agent of citrus brown spot that results in significant yield losses worldwide. Both the production of ACT and the ability to detoxify reactive oxygen species (ROS) are required for A. alternata pathogenicity in citrus. In this study, we report the 34.41 Mb genome sequence of strain Z7 of the tangerine pathotype of A. alternata. The host selective ACT gene cluster in strain Z7 was identified, which included 25 genes with 19 of them not reported previously. Of these, 10 genes were present only in the tangerine pathotype, representing the most likely candidate genes for this pathotype specialization. A transcriptome analysis of the global effects of H2O2 on gene expression revealed 1108 up-regulated and 498 down-regulated genes. Expressions of those genes encoding catalase, peroxiredoxin, thioredoxin and glutathione were highly induced. Genes encoding several protein families including kinases, transcription factors, transporters, cytochrome P450, ubiquitin and heat shock proteins were found associated with adaptation to oxidative stress. Our data not only revealed the molecular basis of ACT biosynthesis but also provided new insights into the potential pathways that the phytopathogen A. alternata copes with oxidative stress. PMID:27582273

  1. Phylogenomic analyses reveal the diversity of laccase-coding genes in Fonsecaea genomes

    Science.gov (United States)

    Feng, Peiying; Weiss, Vinicius Almir; Vicente, Vania Aparecida; Stielow, J. Benjamin; de Hoog, Sybren

    2017-01-01

    The genus Fonsecaea comprises black yeast-like fungi of clinical relevance, including etiologic agents of chromoblastomycosis and cerebral phaeohyphomycosis. Presence of melanin and assimilation of monoaromatic hydrocarbons and alkylbenzenes have been proposed as virulence factors. Multicopper oxidase (MCO) is a family of enzymes including laccases, ferroxidases and ascorbate oxidases which are able to catalyze the oxidation of various aromatic organic compounds with the reduction of molecular oxygen to water. Additionally, laccases are required for the production of fungal melanins, a cell-wall black pigment recognized as a key polymer for pathogenicity and extremotolerance in black yeast-like fungi. Although the activity of laccase enzymes has previously been reported in many wood-rotting fungi, the diversity of laccase genes in Fonsecaea has not yet been assessed. In this study, we identified and characterized laccase-coding genes and determined their genomic location in five clinical and environmental Fonsecaea species. The identification of laccases sensu stricto will provide insights into carbon acquisition strategies as well as melanin production in Fonsecaea. PMID:28187150

  2. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

    Science.gov (United States)

    Lesseur, Corina; Diergaarde, Brenda; Olshan, Andrew F; Wünsch-Filho, Victor; Ness, Andrew R; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, José; Franceschi, Silvia; Lagiou, Pagona; Macfarlane, Gary J; Richiardi, Lorenzo; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Kristina; Zaridze, David; Johansson, Mattias; Menezes, Ana M; Curado, Maria Paula; Robinson, Max; Ahrens, Wolfgang; Canova, Cristina; Znaor, Ariana; Castellsagué, Xavier; Conway, David I; Holcátová, Ivana; Mates, Dana; Vilensky, Marta; Healy, Claire M; Szeszenia-Dąbrowska, Neonila; Fabiánová, Eleonóra; Lissowska, Jolanta; Grandis, Jennifer R; Weissler, Mark C; Tajara, Eloiza H; Nunes, Fabio D; de Carvalho, Marcos B; Thomas, Steve; Hung, Rayjean J; Peters, Wilbert H M; Herrero, Rolando; Cadoni, Gabriella; Bueno-de-Mesquita, H Bas; Steffen, Annika; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valérie; Chabrier, Amélie; Anantharaman, Devasena; Boffetta, Paolo; Amos, Christopher I; McKay, James D; Brennan, Paul

    2016-12-01

    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

  3. Functional and comparative genomics analyses of pmp22 in medaka fish

    Directory of Open Access Journals (Sweden)

    Kawarabayasi Yutaka

    2009-06-01

    Full Text Available Abstract Background Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A. The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV. Several CMT1A model rodents have been established by overexpressing pmp22. Thus, it is thought that pmp22 expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between pmp22 transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for pmp22 regulation by comparative genomics analyses between jawed fishes and mammals. Results A transgenic pmp22 over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS was observed. We successfully confirmed that medaka fish pmp22 has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR. Conclusion Medaka fish undergo abnormalities in the PNS when pmp22 transcription increases. This result indicates that an adequate pmp22 transcription level is necessary for correct myelination of jawed vertebrates. Comparison of pmp22 orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of pmp22 expression.

  4. INNOVATIVE STRATEGIES TO IDENTIFY M. TUBERCULOSIS ANTIGENS AND EPITOPES USING GENOME-WIDE ANALYSES

    Directory of Open Access Journals (Sweden)

    Annemieke eGeluk

    2014-06-01

    Full Text Available In view of the fact that only a small part of the Mtb expressome has been explored for identification of antigens capable of activating human T-cell responses, which is critically required for the design of better TB vaccination strategies, more emphasis should be placed on innovative ways to discover new Mtb antigens and explore their function at the several stages of infection. Better protective antigens for TB vaccines are urgently needed, also in view of the disappointing results of the MVA85 vaccine which failed to induce additional protection in BCG vaccinated infants [54]. Moreover, immune responses to relevant antigens may be useful to identify TB-specific biomarker signatures. Here we describe the potency of novel tools and strategies to reveal such Mtb antigens. Using proteins specific for different Mtb infection phases, many new antigens of the latency-associated Mtb DosR regulon as well as Rpf proteins, associated with resuscitating TB, were discovered that were recognized by CD4+ and CD8+ T-cells. Furthermore, by employing MHC binding algorithms and bioinformatics combined with high throughput human T-cell screens and tetramers, HLA-class Ia restricted poly-functional CD8+ T-cells were identified in TB patients. Comparable methods, led to the identification of HLA-E-restricted Mtb epitopes recognized by CD8+ T-cells. A genome-wide unbiased antigen discovery approach was applied to analyse the in vivo Mtb gene expression profiles in the lungs of mice, resulting in the identification of IVE-TB antigens, which are expressed during infection in the lung, the main target organ of Mtb. IVE-TB antigens induce strong T cell responses in long-term latently Mtb infected individuals, and represent an interesting new group of TB antigens for vaccination. In summary, new tools have helped expand our view on the Mtb antigenome involved in human cellular immunity and provided new candidates for TB vaccination.

  5. Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses.

    Science.gov (United States)

    Demirkan, Ayşe; Henneman, Peter; Verhoeven, Aswin; Dharuri, Harish; Amin, Najaf; van Klinken, Jan Bert; Karssen, Lennart C; de Vries, Boukje; Meissner, Axel; Göraler, Sibel; van den Maagdenberg, Arn M J M; Deelder, André M; C 't Hoen, Peter A; van Duijn, Cornelia M; van Dijk, Ko Willems

    2015-01-01

    Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value  = 1.27×10-32), PRODH with proline (P-value  = 1.11×10-19), SLC16A9 with carnitine level (P-value  = 4.81×10-14) and uncovered a novel association between DMGDH and dimethyl-glycine (P-value  = 1.65×10-19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value  = 1.26×10-8), KCNJ16 with 3-hydroxybutyrate (P-value  = 1.65×10-8) and 2p12 locus with valine (P-value  = 3.49×10-8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the

  6. Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    2015-01-01

    Full Text Available Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS. Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value  = 1.27×10-32, PRODH with proline (P-value  = 1.11×10-19, SLC16A9 with carnitine level (P-value  = 4.81×10-14 and uncovered a novel association between DMGDH and dimethyl-glycine (P-value  = 1.65×10-19 level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value  = 1.26×10-8, KCNJ16 with 3-hydroxybutyrate (P-value  = 1.65×10-8 and 2p12 locus with valine (P-value  = 3.49×10-8. Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL, and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight

  7. The plant ontology as a tool for comparative plant anatomy and genomic analyses

    Science.gov (United States)

    Plant science is now a major player in the fields of genomics, gene expression analysis, phenomics and metabolomics. Recent advances in sequencing technologies have led to a windfall of data, with new species being added rapidly to the list of species whose genomes have been decoded. The Plant Ontol...

  8. Analyses of pig genomes provide insight to procine demography and evolution

    NARCIS (Netherlands)

    Groenen, M.A.M.; Megens, H.J.W.C.; Frantz, L.A.F.; Bosse, M.; Crooijmans, R.P.M.A.; Dibbits, B.W.; Madsen, O.; Paudel, Y.

    2012-01-01

    For 10,000¿years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparis

  9. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance

    Science.gov (United States)

    D’Ursi, Pasqualina; Milanesi, Luciano; Di Canito, Alessandra; Zampolli, Jessica; Collina, Elena; Decorosi, Francesca; Viti, Carlo; Fedi, Stefano; Presentato, Alessandro; Zannoni, Davide; Di Gennaro, Patrizia

    2015-01-01

    In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and environmental decontamination

  10. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance.

    Science.gov (United States)

    Orro, Alessandro; Cappelletti, Martina; D'Ursi, Pasqualina; Milanesi, Luciano; Di Canito, Alessandra; Zampolli, Jessica; Collina, Elena; Decorosi, Francesca; Viti, Carlo; Fedi, Stefano; Presentato, Alessandro; Zannoni, Davide; Di Gennaro, Patrizia

    2015-01-01

    In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and environmental decontamination

  11. Improvement of prediction ability for genomic selection of dairy cattle by including dominance effects.

    Directory of Open Access Journals (Sweden)

    Chuanyu Sun

    Full Text Available Dominance may be an important source of non-additive genetic variance for many traits of dairy cattle. However, nearly all prediction models for dairy cattle have included only additive effects because of the limited number of cows with both genotypes and phenotypes. The role of dominance in the Holstein and Jersey breeds was investigated for eight traits: milk, fat, and protein yields; productive life; daughter pregnancy rate; somatic cell score; fat percent and protein percent. Additive and dominance variance components were estimated and then used to estimate additive and dominance effects of single nucleotide polymorphisms (SNPs. The predictive abilities of three models with both additive and dominance effects and a model with additive effects only were assessed using ten-fold cross-validation. One procedure estimated dominance values, and another estimated dominance deviations; calculation of the dominance relationship matrix was different for the two methods. The third approach enlarged the dataset by including cows with genotype probabilities derived using genotyped ancestors. For yield traits, dominance variance accounted for 5 and 7% of total variance for Holsteins and Jerseys, respectively; using dominance deviations resulted in smaller dominance and larger additive variance estimates. For non-yield traits, dominance variances were very small for both breeds. For yield traits, including additive and dominance effects fit the data better than including only additive effects; average correlations between estimated genetic effects and phenotypes showed that prediction accuracy increased when both effects rather than just additive effects were included. No corresponding gains in prediction ability were found for non-yield traits. Including cows with derived genotype probabilities from genotyped ancestors did not improve prediction accuracy. The largest additive effects were located on chromosome 14 near DGAT1 for yield traits for both

  12. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

    Science.gov (United States)

    Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Cardona Silgado, Julio C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Walkup, John; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G.M.; Yao, Yin; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

    2014-01-01

    Obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS) are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. Here, we report a combined genome-wide association study (GWAS) of TS and OCD in 2723 cases (1310 with OCD, 834 with TS, 579 with OCD plus TS/chronic tics (CT)), 5667 ancestry-matched controls, and 290 OCD parent-child trios. Although no individual single nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels, i.e. expression quantitative loci (eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10−4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, TS had a smaller, non-significant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and TS/CT were included in the analysis (p=0.01). Previous work has shown that TS and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of TS and OCD. Furthermore, OCD with co-occurring TS/CT may have different underlying genetic susceptibility compared to OCD alone. PMID:25158072

  13. Genome-wide analyses of Epstein-Barr virus reveal conserved RNA structures and a novel stable intronic sequence RNA

    OpenAIRE

    2013-01-01

    Background Epstein-Barr virus (EBV) is a human herpesvirus implicated in cancer and autoimmune disorders. Little is known concerning the roles of RNA structure in this important human pathogen. This study provides the first comprehensive genome-wide survey of RNA and RNA structure in EBV. Results Novel EBV RNAs and RNA structures were identified by computational modeling and RNA-Seq analyses of EBV. Scans of the genomic sequences of four EBV strains (EBV-1, EBV-2, GD1, and GD2) and of the clo...

  14. Comparative genomic analyses of Streptococcus mutans provide insights into chromosomal shuffling and species-specific content

    Directory of Open Access Journals (Sweden)

    Nakai Kenta

    2009-08-01

    Full Text Available Abstract Background Streptococcus mutans is the major pathogen of dental caries, and it occasionally causes infective endocarditis. While the pathogenicity of this species is distinct from other human pathogenic streptococci, the species-specific evolution of the genus Streptococcus and its genomic diversity are poorly understood. Results We have sequenced the complete genome of S. mutans serotype c strain NN2025, and compared it with the genome of UA159. The NN2025 genome is composed of 2,013,587 bp, and the two strains show highly conserved core-genome. However, comparison of the two S. mutans strains showed a large genomic inversion across the replication axis producing an X-shaped symmetrical DNA dot plot. This phenomenon was also observed between other streptococcal species, indicating that streptococcal genetic rearrangements across the replication axis play an important role in Streptococcus genetic shuffling. We further confirmed the genomic diversity among 95 clinical isolates using long-PCR analysis. Genomic diversity in S. mutans appears to occur frequently between insertion sequence (IS elements and transposons, and these diversity regions consist of restriction/modification systems, antimicrobial peptide synthesis systems, and transporters. S. mutans may preferentially reject the phage infection by clustered regularly interspaced short palindromic repeats (CRISPRs. In particular, the CRISPR-2 region, which is highly divergent between strains, in NN2025 has long repeated spacer sequences corresponding to the streptococcal phage genome. Conclusion These observations suggest that S. mutans strains evolve through chromosomal shuffling and that phage infection is not needed for gene acquisition. In contrast, S. pyogenes tolerates phage infection for acquisition of virulence determinants for niche adaptation.

  15. Genome and metagenome analyses reveal adaptive evolution of the host and interaction with the gut microbiota in the goose

    Science.gov (United States)

    Gao, Guangliang; Zhao, Xianzhi; Li, Qin; He, Chuan; Zhao, Wenjing; Liu, Shuyun; Ding, Jinmei; Ye, Weixing; Wang, Jun; Chen, Ye; Wang, Haiwei; Li, Jing; Luo, Yi; Su, Jian; Huang, Yong; Liu, Zuohua; Dai, Ronghua; Shi, Yixiang; Meng, He; Wang, Qigui

    2016-01-01

    The goose is an economically important waterfowl that exhibits unique characteristics and abilities, such as liver fat deposition and fibre digestion. Here, we report de novo whole-genome assemblies for the goose and swan goose and describe the evolutionary relationships among 7 bird species, including domestic and wild geese, which diverged approximately 3.4~6.3 million years ago (Mya). In contrast to chickens as a proximal species, the expanded and rapidly evolving genes found in the goose genome are mainly involved in metabolism, including energy, amino acid and carbohydrate metabolism. Further integrated analysis of the host genome and gut metagenome indicated that the most widely shared functional enrichment of genes occurs for functions such as glycolysis/gluconeogenesis, starch and sucrose metabolism, propanoate metabolism and the citrate cycle. We speculate that the unique physiological abilities of geese benefit from the adaptive evolution of the host genome and symbiotic interactions with gut microbes. PMID:27608918

  16. Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses

    NARCIS (Netherlands)

    O'Connell, R.J.; Thon, M.R.; Hacquard, S.; Amyotte, S.G.; Kleemann, J.; Torres, M.F.; Damm, U.; Buiate, E.A.; Epstein, L.; Alkan, N.; Altmuller, J.; Alvarado-Balderrama, L.; Bauser, C.A.; Becker, C.; Birren, B.W.; Chen, Z.; Choi, J.; Crouch, J.A.; Duvick, J.P.; Farman, M.A.; Gan, P.; Heiman, D.; Henrissat, B.; Howard, R.J.; Kabbage, M.; Koch, C.; Kracher, B.; Kubo, Y.; Law, A.D.; Lebrun, M.-H.; Lee, Y.-H.; Miyara, I.; Moore, N.; Neumann, U.; Nordstrom, K.; Panaccione, D.G.; Panstruga, R.; Place, M.; Proctor, R.H.; Prusky, D.; Rech, G.; Reinhardt, R.; Rollins, J.A.; Rounsley, S.; Schardl, C.L.; Schwartz, D.C.; Shenoy, N.; Shirasu, K.; Sikhakolli, U.R.; Stuber, K.; Sukno, S.A.; Sweigard, J.A.; Takano, Y.; Takahara, H.; Trail, F.; Does, H.C.; Voll, L.M.; Will, I.; Young, S.; Zeng, Q.; Zhang, Jingze; Zhou, S.; Dickman, M.B.; Schulze-Lefert, P.; Verloren van Themaat, E.; Ma, L.-J.; Vaillancourt, L.J.

    2012-01-01

    Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and

  17. Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses

    NARCIS (Netherlands)

    O'Connell, R.J.; Thon, M.R.; Hacquard, S.; Amyotte, S.G.; Kleemann, J.; Torres, M.F.; Damm, U.; Buiate, E.A.; Epstein, L.; Alkan, N.; Altmuller, J.; Alvarado-Balderrama, L.; Bauser, C.A.; Becker, C.; Birren, B.W.; Chen, Z.; Choi, J.; Crouch, J.A.; Duvick, J.P.; Farman, M.A.; Gan, P.; Heiman, D.; Henrissat, B.; Howard, R.J.; Kabbage, M.; Koch, C.; Kracher, B.; Kubo, Y.; Law, A.D.; Lebrun, M.-H.; Lee, Y.-H.; Miyara, I.; Moore, N.; Neumann, U.; Nordstrom, K.; Panaccione, D.G.; Panstruga, R.; Place, M.; Proctor, R.H.; Prusky, D.; Rech, G.; Reinhardt, R.; Rollins, J.A.; Rounsley, S.; Schardl, C.L.; Schwartz, D.C.; Shenoy, N.; Shirasu, K.; Sikhakolli, U.R.; Stuber, K.; Sukno, S.A.; Sweigard, J.A.; Takano, Y.; Takahara, H.; Trail, F.; Does, H.C.; Voll, L.M.; Will, I.; Young, S.; Zeng, Q.; Zhang, Jingze; Zhou, S.; Dickman, M.B.; Schulze-Lefert, P.; Verloren van Themaat, E.; Ma, L.-J.; Vaillancourt, L.J.

    2012-01-01

    Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and tr

  18. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Science.gov (United States)

    Egan, Jan B; Barrett, Michael T; Champion, Mia D; Middha, Sumit; Lenkiewicz, Elizabeth; Evers, Lisa; Francis, Princy; Schmidt, Jessica; Shi, Chang-Xin; Van Wier, Scott; Badar, Sandra; Ahmann, Gregory; Kortuem, K Martin; Boczek, Nicole J; Fonseca, Rafael; Craig, David W; Carpten, John D; Borad, Mitesh J; Stewart, A Keith

    2014-01-01

    Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  19. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan B Egan

    Full Text Available Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  20. Whole-genome analyses resolve early branches in the tree of life of modern birds

    DEFF Research Database (Denmark)

    Sicheritz-Pontén, Thomas; Li, Cai; Li, Bo

    2014-01-01

    To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or ...... levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago....

  1. A complete sequence and transcriptomic analyses of date palm (Phoenix dactylifera L. mitochondrial genome.

    Directory of Open Access Journals (Sweden)

    Yongjun Fang

    Full Text Available Based on next-generation sequencing data, we assembled the mitochondrial (mt genome of date palm (Phoenix dactylifera L. into a circular molecule of 715,001 bp in length. The mt genome of P. dactylifera encodes 38 proteins, 30 tRNAs, and 3 ribosomal RNAs, which constitute a gene content of 6.5% (46,770 bp over the full length. The rest, 93.5% of the genome sequence, is comprised of cp (chloroplast-derived (10.3% with respect to the whole genome length and non-coding sequences. In the non-coding regions, there are 0.33% tandem and 2.3% long repeats. Our transcriptomic data from eight tissues (root, seed, bud, fruit, green leaf, yellow leaf, female flower, and male flower showed higher gene expression levels in male flower, root, bud, and female flower, as compared to four other tissues. We identified 120 potential SNPs among three date palm cultivars (Khalas, Fahal, and Sukry, and successfully found seven SNPs in the coding sequences. A phylogenetic analysis, based on 22 conserved genes of 15 representative plant mitochondria, showed that P. dactylifera positions at the root of all sequenced monocot mt genomes. In addition, consistent with previous discoveries, there are three co-transcribed gene clusters-18S-5S rRNA, rps3-rpl16 and nad3-rps12-in P. dactylifera, which are highly conserved among all known mitochondrial genomes of angiosperms.

  2. Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials.

    NARCIS (Netherlands)

    Keus, F.; Wetterslev, J.; Gluud, C.; Gooszen, H.G.; Laarhoven, C.J.H.M. van

    2009-01-01

    OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical metho

  3. Robustness Assessments Are Needed to Reduce Bias in Meta-Analyses That Include Zero-Event Randomized Trials

    NARCIS (Netherlands)

    Keus, F.; Wetterslev, J.; Gluud, C.; Gooszen, H. G.; van Laarhoven, C. J. H. M.

    2009-01-01

    OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical metho

  4. A novel application of ecological analyses to assess transposable element distributions in the genome of the domestic cow, Bos taurus.

    Science.gov (United States)

    Saylor, Brent; Elliott, Tyler A; Linquist, Stefan; Kremer, Stefan C; Gregory, T Ryan; Cottenie, Karl

    2013-09-01

    Transposable elements (TEs) are among the most abundant components of many eukaryotic genomes. Efforts to explain TE abundance, as well as TE diversity among genomes, have led some researchers to draw an analogy between genomic and ecological processes. Adopting this perspective, we conducted an analysis of the cow (Bos taurus) genome using techniques developed by community ecologists to determine whether environmental factors influence community composition. Specifically, each chromosome within the Bos taurus genome was treated as a "linear transect", and a multivariate redundancy analysis (RDA) was used to identify large-scale spatial patterns in TE communities associated with 10 TE families. The position of each TE community on the chromosome accounted for ∼50% of the variation along the chromosome "transect". Multivariate analysis further revealed an effect of gene density on TE communities that is influenced by several other factors in the (genomic) environment, including chromosome length and TE density. The results of this analysis demonstrate that ecological methods can be applied successfully to help answer genomic questions.

  5. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism.

    Science.gov (United States)

    Parikshak, Neelroop N; Luo, Rui; Zhang, Alice; Won, Hyejung; Lowe, Jennifer K; Chandran, Vijayendran; Horvath, Steve; Geschwind, Daniel H

    2013-11-21

    Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: (1) do these genetic loci converge on specific biological processes, and (2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto coexpression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortical laminae. ASD genes tightly coalesce in modules that implicate distinct biological functions during human cortical development, including early transcriptional regulation and synaptic development. Bioinformatic analyses suggest that translational regulation by FMRP and transcriptional coregulation by common transcription factors connect these processes. At a circuit level, ASD genes are enriched in superficial cortical layers and glutamatergic projection neurons. Furthermore, we show that the patterns of ASD and ID risk genes are distinct, providing a biological framework for further investigating the pathophysiology of ASD.

  6. Comparative and Transcriptome Analyses Uncover Key Aspects of Coding- and Long Noncoding RNAs in Flatworm Mitochondrial Genomes

    Directory of Open Access Journals (Sweden)

    Eric Ross

    2016-05-01

    Full Text Available Exploiting the conservation of various features of mitochondrial genomes has been instrumental in resolving phylogenetic relationships. Despite extensive sequence evidence, it has not previously been possible to conclusively resolve some key aspects of flatworm mitochondrial genomes, including generally conserved traits, such as start codons, noncoding regions, the full complement of tRNAs, and whether ATP8 is, or is not, encoded by this extranuclear genome. In an effort to address these difficulties, we sought to determine the mitochondrial transcriptomes and genomes of sexual and asexual taxa of freshwater triclads, a group previously poorly represented in flatworm mitogenomic studies. We have discovered evidence for an alternative start codon, an extended cox1 gene, a previously undescribed conserved open reading frame, long noncoding RNAs, and a highly conserved gene order across the large evolutionary distances represented within the triclads. Our findings contribute to the expansion and refinement of mitogenomics to address evolutionary issues in this diverse group of animals.

  7. Gene set analyses of genome-wide association studies on 49 quantitative traits measured in a single genetic epidemiology dataset.

    Science.gov (United States)

    Kim, Jihye; Kwon, Ji-Sun; Kim, Sangsoo

    2013-09-01

    Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP) genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO) terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr neuronal or nerve systems.

  8. Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY-1.

    Science.gov (United States)

    Yang, Yue; Liu, Bin; Du, Xinjun; Li, Ping; Liang, Bin; Cheng, Xiaozhen; Du, Liangcheng; Huang, Di; Wang, Lei; Wang, Shuo

    2015-02-09

    Monascus has been used to produce natural colorants and food supplements for more than one thousand years, and approximately more than one billion people eat Monascus-fermented products during their daily life. In this study, using next-generation sequencing and optical mapping approaches, a 24.1-Mb complete genome of an industrial strain, Monascus purpureus YY-1, was obtained. This genome consists of eight chromosomes and 7,491 genes. Phylogenetic analysis at the genome level provides convincing evidence for the evolutionary position of M. purpureus. We provide the first comprehensive prediction of the biosynthetic pathway for Monascus pigment. Comparative genomic analyses show that the genome of M. purpureus is 13.6-40% smaller than those of closely related filamentous fungi and has undergone significant gene losses, most of which likely occurred during its specialized adaptation to starch-based foods. Comparative transcriptome analysis reveals that carbon starvation stress, resulting from the use of relatively low-quality carbon sources, contributes to the high yield of pigments by repressing central carbon metabolism and augmenting the acetyl-CoA pool. Our work provides important insights into the evolution of this economically important fungus and lays a foundation for future genetic manipulation and engineering of this strain.

  9. CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening

    DEFF Research Database (Denmark)

    Wang, M.J.; Lamberth, K.; Harndahl, M.

    2007-01-01

    are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen......-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential....

  10. The complete mitochondrial genome of Gastrothylax crumenifer (Gastrothylacidae, Trematoda) and comparative analyses with selected trematodes.

    Science.gov (United States)

    Yang, Xin; Wang, Lixia; Chen, Hongmei; Feng, Hanli; Shen, Bang; Hu, Min; Fang, Rui

    2016-06-01

    In the present study, we sequenced and analyzed the mitochondrial (mt) genome of Gastrothylax crumenifer and compared it with other selected trematodes. The full mt genome of G. crumenifer was amplified, sequenced, assembled, analyzed and then subjected to phylogenetic analysis. The complete mt genome of G. crumenifer is 14,801 bp in length and contains two rRNA genes, two non-coding regions (LNR and SNR), 12 protein-coding genes, and 22 transfer RNA genes. The gene organization of the G. crumenifer mt genome is the same as that of other trematodes, except for Schistosoma haematobium and Schistosoma spindale. All the genes are transcribed in the same direction and rich in "A + T", which is in accordance with other trematodes, such as Fasciola hepatica, Paramphistomum cervi, and Fischoederius elongatus. Phylogenetic analysis using concatenated amino acid sequences of the 12 protein-coding genes showed that G. crumenifer is closely related to F. elongatus. The availability of mt genome sequence of G. crumenifer can provide useful DNA markers for studying the molecular epidemiology and population genetics of this parasite and other paramphistomes.

  11. Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

    OpenAIRE

    2014-01-01

    Aim Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. Methods We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal ti...

  12. Comparative transcriptome and chloroplast genome analyses of two related Dipteronia species

    Directory of Open Access Journals (Sweden)

    Tao Zhou

    2016-10-01

    Full Text Available Dipteronia (order Sapindales is an endangered genus endemic to China and has two living species, D. sinensis and D. dyeriana. The plants are closely related to the genus Acer, which is also classified in the order Sapindales. Evolutionary studies on Dipteronia have been hindered by the paucity of information on their genomes and plastids. Here, we used next generation sequencing to characterize the transcriptomes and complete chloroplast genomes of both Dipteronia species. A comparison of the transcriptomes of both species identified a total of 7,814 orthologs. Estimation of selection pressures using Ka/Ks ratios showed that only 30 of 5,435 orthologous pairs had a ratio significantly greater than 1, i.e., showing positive selection. However, 4,041 orthologs had a Ka/Ks < 0.5 (p < 0.05, suggesting that most genes had likely undergone purifying selection. Based on orthologous unigenes, 314 single copy nuclear genes were identified. Through a combination of de novo and reference guided assembly, plastid genomes were obtained; that of D. sinensis was 157,080 bp and that of D. dyeriana was 157,071 bp. Both plastid genomes encoded 87 protein coding genes, 40 tRNAs, and 8 rRNAs; no significant differences were detected in the size, gene content, and organization of the two plastomes. We used the whole chloroplast genomes to determine the phylogeny of D. sinensis and D. dyeriana and confirmed that the two species were highly divergent. Overall, our study provides comprehensive transcriptomic and chloroplast genomic resources, which will be valuable for future evolutionary studies of Dipteronia.

  13. Combinatory microarray and SuperSAGE analyses identify pairing-dependently transcribed genes in Schistosoma mansoni males, including follistatin.

    Directory of Open Access Journals (Sweden)

    Silke Leutner

    2013-11-01

    Full Text Available BACKGROUND: Schistosomiasis is a disease of world-wide importance and is caused by parasitic flatworms of the genus Schistosoma. These parasites exhibit a unique reproduction biology as the female's sexual maturation depends on a constant pairing-contact to the male. Pairing leads to gonad differentiation in the female, and even gene expression of some gonad-associated genes is controlled by pairing. In contrast, no morphological changes have been observed in males, although first data indicated an effect of pairing also on gene transcription in males. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the influence of pairing on males, we performed a combinatory approach applying SuperSAGE and microarray hybridization, generating the most comprehensive data-set on differential transcription available to date. Of 6,326 sense transcripts detected by both analyses, 29 were significantly differentially transcribed. Besides mutual confirmation, the two methods complemented each other as shown by data comparison and real-time PCR, which revealed a number of genes with consistent regulation across all methods. One of the candidate genes, follistatin of S. mansoni (SmFst was characterized in more detail by in situ hybridization and yeast two-hybrid (Y2H interaction analyses with potential binding partners. CONCLUSIONS/SIGNIFICANCE: Beyond confirming previously hypothesized differences in metabolic processes between pairing-experienced (EM and pairing-unexperienced males (UM, our data indicate that neuronal processes are involved in male-female interaction but also TGFβ-signaling. One candidate revealing significant down-regulation in EM was the TGFβ-pathway controlling molecule follistatin (SmFst. First functional analyses demonstrated SmFst interaction with the S. mansoni TGFβ-receptor agonists inhibin/activin (SmInAct and bone morphogenic protein (SmBMP, and all molecules colocalized in the testes. This indicates a yet unknown role of the TGF

  14. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  15. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove

  16. Genomic analyses of DNA transformation and penicillin resistance in Streptococcus pneumoniae clinical isolates.

    Science.gov (United States)

    Fani, Fereshteh; Leprohon, Philippe; Zhanel, George G; Bergeron, Michel G; Ouellette, Marc

    2014-01-01

    Alterations in penicillin-binding proteins, the target enzymes for β-lactam antibiotics, are recognized as primary penicillin resistance mechanisms in Streptococcus pneumoniae. Few studies have analyzed penicillin resistance at the genome scale, however, and we report the sequencing of S. pneumoniae R6 transformants generated while reconstructing the penicillin resistance phenotypes from three penicillin-resistant clinical isolates by serial genome transformation. The genome sequences of the three last-level transformants T2-18209, T5-1983, and T3-55938 revealed that 16.2 kb, 82.7 kb, and 137.2 kb of their genomes had been replaced with 5, 20, and 37 recombinant sequence segments derived from their respective parental clinical isolates, documenting the extent of DNA transformation between strains. A role in penicillin resistance was confirmed for some of the mutations identified in the transformants. Several multiple recombination events were also found to have happened at single loci coding for penicillin-binding proteins (PBPs) that increase resistance. Sequencing of the transformants with MICs for penicillin similar to those of the parent clinical strains confirmed the importance of mosaic PBP2x, -2b, and -1a as a driving force in penicillin resistance. A role in resistance for mosaic PBP2a was also observed for two of the resistant clinical isolates.

  17. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with se

  18. Genome-wide association analyses identify variants in developmental genes associated with hypospadias

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Carstensen, Lisbeth

    2014-01-01

    Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1...

  19. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  20. The chloroplast genome of the hexaploid Spartina maritima (Poaceae, Chloridoideae): Comparative analyses and molecular dating.

    Science.gov (United States)

    Rousseau-Gueutin, M; Bellot, S; Martin, G E; Boutte, J; Chelaifa, H; Lima, O; Michon-Coudouel, S; Naquin, D; Salmon, A; Ainouche, K; Ainouche, M

    2015-12-01

    The history of many plant lineages is complicated by reticulate evolution with cases of hybridization often followed by genome duplication (allopolyploidy). In such a context, the inference of phylogenetic relationships and biogeographic scenarios based on molecular data is easier using haploid markers like chloroplast genome sequences. Hybridization and polyploidization occurred recurrently in the genus Spartina (Poaceae, Chloridoideae), as illustrated by the recent formation of the invasive allododecaploid S. anglica during the 19th century in Europe. Until now, only a few plastid markers were available to explore the history of this genus and their low variability limited the resolution of species relationships. We sequenced the complete chloroplast genome (plastome) of S. maritima, the native European parent of S. anglica, and compared it to the plastomes of other Poaceae. Our analysis revealed the presence of fast-evolving regions of potential taxonomic, phylogeographic and phylogenetic utility at various levels within the Poaceae family. Using secondary calibrations, we show that the tetraploid and hexaploid lineages of Spartina diverged 6-10 my ago, and that the two parents of the invasive allopolyploid S. anglica separated 2-4 my ago via long distance dispersal of the ancestor of S. maritima over the Atlantic Ocean. Finally, we discuss the meaning of divergence times between chloroplast genomes in the context of reticulate evolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and it

  2. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  3. Analyses of pig genomes provide insight into porcine demography and evolution

    Science.gov (United States)

    Groenen, Martien A. M.; Archibald, Alan L.; Uenishi, Hirohide; Tuggle, Christopher K.; Takeuchi, Yasuhiro; Rothschild, Max F.; Rogel-Gaillard, Claire; Park, Chankyu; Milan, Denis; Megens, Hendrik-Jan; Li, Shengting; Larkin, Denis M.; Kim, Heebal; Frantz, Laurent A. F.; Caccamo, Mario; Ahn, Hyeonju; Aken, Bronwen L.; Anselmo, Anna; Anthon, Christian; Auvil, Loretta; Badaoui, Bouabid; Beattie, Craig W.; Bendixen, Christian; Berman, Daniel; Blecha, Frank; Blomberg, Jonas; Bolund, Lars; Bosse, Mirte; Botti, Sara; Bujie, Zhan; Bystrom, Megan; Capitanu, Boris; Silva, Denise Carvalho; Chardon, Patrick; Chen, Celine; Cheng, Ryan; Choi, Sang-Haeng; Chow, William; Clark, Richard C.; Clee, Christopher; Crooijmans, Richard P. M. A.; Dawson, Harry D.; Dehais, Patrice; De Sapio, Fioravante; Dibbits, Bert; Drou, Nizar; Du, Zhi-Qiang; Eversole, Kellye; Fadista, João; Fairley, Susan; Faraut, Thomas; Faulkner, Geoffrey J.; Fowler, Katie E.; Fredholm, Merete; Fritz, Eric; Gilbert, James G. R.; Giuffra, Elisabetta; Gorodkin, Jan; Griffin, Darren K.; Harrow, Jennifer L.; Hayward, Alexander; Howe, Kerstin; Hu, Zhi-Liang; Humphray, Sean J.; Hunt, Toby; Hornshøj, Henrik; Jeon, Jin-Tae; Jern, Patric; Jones, Matthew; Jurka, Jerzy; Kanamori, Hiroyuki; Kapetanovic, Ronan; Kim, Jaebum; Kim, Jae-Hwan; Kim, Kyu-Won; Kim, Tae-Hun; Larson, Greger; Lee, Kyooyeol; Lee, Kyung-Tai; Leggett, Richard; Lewin, Harris A.; Li, Yingrui; Liu, Wansheng; Loveland, Jane E.; Lu, Yao; Lunney, Joan K.; Ma, Jian; Madsen, Ole; Mann, Katherine; Matthews, Lucy; McLaren, Stuart; Morozumi, Takeya; Murtaugh, Michael P.; Narayan, Jitendra; Nguyen, Dinh Truong; Ni, Peixiang; Oh, Song-Jung; Onteru, Suneel; Panitz, Frank; Park, Eung-Woo; Park, Hong-Seog; Pascal, Geraldine; Paudel, Yogesh; Perez-Enciso, Miguel; Ramirez-Gonzalez, Ricardo; Reecy, James M.; Zas, Sandra Rodriguez; Rohrer, Gary A.; Rund, Lauretta; Sang, Yongming; Schachtschneider, Kyle; Schraiber, Joshua G.; Schwartz, John; Scobie, Linda; Scott, Carol; Searle, Stephen; Servin, Bertrand; Southey, Bruce R.; Sperber, Goran; Stadler, Peter; Sweedler, Jonathan V.; Tafer, Hakim; Thomsen, Bo; Wali, Rashmi; Wang, Jian; Wang, Jun; White, Simon; Xu, Xun; Yerle, Martine; Zhang, Guojie; Zhang, Jianguo; Zhang, Jie; Zhao, Shuhong; Rogers, Jane; Churcher, Carol; Schook, Lawrence B.

    2013-01-01

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model. PMID:23151582

  4. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove

  5. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analys

  6. MRSA transmission on a neonatal intensive care unit: epidemiological and genome-based phylogenetic analyses.

    Directory of Open Access Journals (Sweden)

    Ulrich Nübel

    Full Text Available BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs. While the specific factors favouring MRSA spread on neonatal wards are not well understood, colonized infants, their relatives, or health-care workers may all be sources for MRSA transmission. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale. METHODS AND FINDINGS: We applied whole-genome sequencing to trace MRSA spread in a NICU and performed a case-control study to identify risk factors for MRSA transmission. MRSA genomes had accumulated sequence variation sufficiently fast to reflect epidemiological linkage among individual patients, between infants and their mothers, and between infants and staff members, such that the relevance of individual nurses' nasal MRSA colonization for prolonged transmission could be evaluated. In addition to confirming previously reported risk factors, we identified an increased risk of transmission from infants with as yet unknown MRSA colonisation, in contrast to known MRSA-positive infants. CONCLUSIONS: The integration of epidemiological (temporal, spatial and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit. The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA.

  7. Genome constitution of Narcissus variety, 'Tete-a-Tete', analysed through GISH and NBS profiling

    NARCIS (Netherlands)

    Wu, H.; Ramanna, M.S.; Arens, P.; Tuyl, van J.M.

    2011-01-01

    The Narcissus variety, ‘Tête-à-Tête’, has been the most popular variety since 1949, and a well known allotriploid (2n = 3x = 24 + B) of spontaneous origin. Because the identity of one of the parents of this variety was uncertain, the genome constitution of ‘Tête-à-Tête’ was investigated by using gen

  8. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  9. Genome constitution of Narcissus variety, 'Tete-a-Tete', analysed through GISH and NBS profiling

    NARCIS (Netherlands)

    Wu, H.; Ramanna, M.S.; Arens, P.; Tuyl, van J.M.

    2011-01-01

    The Narcissus variety, ‘Tête-à-Tête’, has been the most popular variety since 1949, and a well known allotriploid (2n = 3x = 24 + B) of spontaneous origin. Because the identity of one of the parents of this variety was uncertain, the genome constitution of ‘Tête-à-Tête’ was investigated by using gen

  10. Metabolic model for the filamentous ‘Candidatus Microthrix parvicella’ based on genomic and metagenomic analyses

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Kristiansen, Rikke; Albertsen, Mads;

    2013-01-01

    acids as triacylglycerols. Utilisation of trehalose and/or polyphosphate stores or partial oxidation of long-chain fatty acids may supply the energy required for anaerobic lipid uptake and storage. Comparing the genome sequence of this isolate with metagenomes from two full-scale wastewater treatment...

  11. Genome sequencing and analyses of the postharvest fungus Penicillium expansum R21

    Science.gov (United States)

    Blue mold is the vernacular name of a common postharvest disease of stored apples, pears and quince that is caused by several common species of Penicillium. This study reports the draft genome sequence of Penicillium expansum strain R21, a strain isolated from a Red Delicious apple in 2011 in Pennsy...

  12. Pedigree and genomic analyses of feed consumption and residual feed intake in laying hens.

    Science.gov (United States)

    Wolc, Anna; Arango, Jesus; Jankowski, Tomasz; Settar, Petek; Fulton, Janet E; O'Sullivan, Neil P; Fernando, Rohan; Garrick, Dorian J; Dekkers, Jack C M

    2013-09-01

    Efficiency of production is increasingly important with the current escalation of feed costs and demands to minimize the environmental footprint. The objectives of this study were 1) to estimate heritabilities for daily feed consumption and residual feed intake and their genetic correlations with production and egg-quality traits; 2) to evaluate accuracies of estimated breeding values from pedigree- and marker-based prediction models; and 3) to localize genomic regions associated with feed efficiency in a brown egg layer line. Individual feed intake data collected over 2-wk trial periods were available for approximately 6,000 birds from 8 generations. Genetic parameters were estimated with a multitrait animal model; methods BayesB and BayesCπ were used to estimate marker effects and find genomic regions associated with feed efficiency. Using pedigree information, feed efficiency was found to be moderately heritable (h(2) = 0.46 for daily feed consumption and 0.47 for residual feed intake). Hens that consumed more feed and had greater residual feed intake (lower efficiency) had a genetic tendency to lay slightly more eggs with greater yolk weights and albumen heights. Regions on chromosomes 1, 2, 4, 7, 13, and Z were found to be associated with feed intake and efficiency. The accuracy from genomic prediction was higher and more persistent (better maintained across generations) than that from pedigree-based prediction. These results indicate that genomic selection can be used to improve feed efficiency in layers.

  13. Acinetobacter seifertii Isolated from China: Genomic Sequence and Molecular Epidemiology Analyses.

    Science.gov (United States)

    Yang, Yunxing; Wang, Jianfeng; Fu, Ying; Ruan, Zhi; Yu, Yunsong

    2016-03-01

    Clinical infections caused by Acinetobacter spp. have increasing public health concerns because of their global occurrence and ability to acquire multidrug resistance. Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex encompasses A. calcoaceticus, A. baumannii, A. pittii (formerly genomic species 3), and A nosocomial (formerly genomic species 13TU), which are predominantly responsible for clinical pathogenesis in the Acinetobacter genus. In our previous study, a putative novel species isolated from 385 non-A. baumannii spp. strains based on the rpoB gene phylogenetic tree was reported. Here, the putative novel species was identified as A. seifertii based on the whole-genome phylogenetic tree. A. seifertii was recognized as a novel member of the ACB complex and close to A. baumannii and A. nosocomials. Furthermore, we studied the characteristics of 10 A. seifertii isolates, which were distributed widely in 6 provinces in China and mainly caused infections in the elderly or children. To define the taxonomic status and characteristics, the biochemical reactions, antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and whole-genome sequence analysis were performed. The phenotypic characteristics failed to distinguish A. serfertii from other species in the ACB complex. Most of the A. seifertii isolates were susceptible to antibiotics commonly used for nosocomial Acinetobacter spp. infections, but one isolate (strain A362) was resistant to ampicillin/sulbactam, ceftazidime and amikacin. The different patterns of MLST and PFGE suggested that the 10 isolates were not identical and lacked clonal relatedness. Our study reported for the first time the molecular epidemiological and genomic features of widely disseminated A. seifertii in China. These observations could enrich the knowledge of infections caused by non-A. baumannii and may provide a scientific basis for future clinical treatment.

  14. A whole genome analyses of genetic variants in two Kelantan Malay individuals.

    Science.gov (United States)

    Wan Juhari, Wan Khairunnisa; Md Tamrin, Nur Aida; Mat Daud, Mohd Hanif Ridzuan; Isa, Hatin Wan; Mohd Nasir, Nurfazreen; Maran, Sathiya; Abdul Rajab, Nur Shafawati; Ahmad Amin Noordin, Khairul Bariah; Nik Hassan, Nik Norliza; Tearle, Rick; Razali, Rozaimi; Merican, Amir Feisal; Zilfalil, Bin Alwi

    2014-12-01

    The sequencing of two members of the Royal Kelantan Malay family genomes will provide insights on the Kelantan Malay whole genome sequences. The two Kelantan Malay genomes were analyzed for the SNP markers associated with thalassemia and Helicobacter pylori infection. Helicobacter pylori infection was reported to be low prevalence in the north-east as compared to the west coast of the Peninsular Malaysia and beta-thalassemia was known to be one of the most common inherited and genetic disorder in Malaysia. By combining SNP information from literatures, GWAS study and NCBI ClinVar, 18 unique SNPs were selected for further analysis. From these 18 SNPs, 10 SNPs came from previous study of Helicobacter pylori infection among Malay patients, 6 SNPs were from NCBI ClinVar and 2 SNPs from GWAS studies. The analysis reveals that both Royal Kelantan Malay genomes shared all the 10 SNPs identified by Maran (Single Nucleotide Polymorphims (SNPs) genotypic profiling of Malay patients with and without Helicobacter pylori infection in Kelantan, 2011) and one SNP from GWAS study. In addition, the analysis also reveals that both Royal Kelantan Malay genomes shared 3 SNP markers; HBG1 (rs1061234), HBB (rs1609812) and BCL11A (rs766432) where all three markers were associated with beta-thalassemia. Our findings suggest that the Royal Kelantan Malays carry the SNPs which are associated with protection to Helicobacter pylori infection. In addition they also carry SNPs which are associated with beta-thalassemia. These findings are in line with the findings by other researchers who conducted studies on thalassemia and Helicobacter pylori infection in the non-royal Malay population.

  15. Genome-wide and molecular evolution analyses of the phospholipase D gene family in Poplar and Grape.

    Science.gov (United States)

    Liu, Qi; Zhang, Chiyu; Yang, Yongping; Hu, Xiangyang

    2010-06-18

    The Phospholipase D (PLD) family plays an important role in the regulation of cellular processes in plants, including abscisic acid signaling, programmed cell death, root hair patterning, root growth, freezing tolerance and other stress responses. PLD genes constitute an important gene family in higher plants. However, until now our knowledge concerning the PLD gene family members and their evolutionary relationship in woody plants such as Poplar and Grape has been limited. In this study, we have provided a genome-wide analysis of the PLD gene family in Poplar and Grape. Eighteen and eleven members of the PLD gene family were identified in Poplar and Grape respectively. Phylogenetic and gene structure analyses showed that the PLD gene family can be divided into 6 subgroups: alpha, beta/gamma, delta, epsilon, zeta, and phi, and that the 6 PLD subgroups originated from 4 original ancestors through a series of gene duplications. Interestingly, the majority of the PLD genes from both Poplar (76.5%, 13/17) and Grape (90.9%, 10/11) clustered closely together in the phylogenetic tree to the extent that their evolutionary relationship appears more tightly linked to each other, at least in terms of the PLD gene family, than it does to either Arabidopsis or rice. Five pairs of duplicated PLD genes were identified in Poplar, more than those in Grape, suggesting that frequent gene duplications occurred after these species diverged, resulting in a rapid expansion of the PLD gene family in Poplar. The majority of the gene duplications in Poplar were caused by segmental duplication and were distinct from those in Arabidopsis, rice and Grape. Additionally, the gene duplications in Poplar were estimated to have occurred from 11.31 to 13.76 million years ago, which are later than those that occurred in the other three plant species. Adaptive evolution analysis showed that positive selection contributed to the evolution of the PXPH- and SP-PLDs, whereas purifying selection has driven

  16. Genome-wide and molecular evolution analyses of the phospholipase D gene family in Poplar and Grape

    Directory of Open Access Journals (Sweden)

    Yang Yongping

    2010-06-01

    Full Text Available Abstract Background The Phospholipase D (PLD family plays an important role in the regulation of cellular processes in plants, including abscisic acid signaling, programmed cell death, root hair patterning, root growth, freezing tolerance and other stress responses. PLD genes constitute an important gene family in higher plants. However, until now our knowledge concerning the PLD gene family members and their evolutionary relationship in woody plants such as Poplar and Grape has been limited. Results In this study, we have provided a genome-wide analysis of the PLD gene family in Poplar and Grape. Eighteen and eleven members of the PLD gene family were identified in Poplar and Grape respectively. Phylogenetic and gene structure analyses showed that the PLD gene family can be divided into 6 subgroups: α, β/γ, δ, ε, ζ, and φ, and that the 6 PLD subgroups originated from 4 original ancestors through a series of gene duplications. Interestingly, the majority of the PLD genes from both Poplar (76.5%, 13/17 and Grape (90.9%, 10/11 clustered closely together in the phylogenetic tree to the extent that their evolutionary relationship appears more tightly linked to each other, at least in terms of the PLD gene family, than it does to either Arabidopsis or rice. Five pairs of duplicated PLD genes were identified in Poplar, more than those in Grape, suggesting that frequent gene duplications occurred after these species diverged, resulting in a rapid expansion of the PLD gene family in Poplar. The majority of the gene duplications in Poplar were caused by segmental duplication and were distinct from those in Arabidopsis, rice and Grape. Additionally, the gene duplications in Poplar were estimated to have occurred from 11.31 to 13.76 million years ago, which are later than those that occurred in the other three plant species. Adaptive evolution analysis showed that positive selection contributed to the evolution of the PXPH- and SP-PLDs, whereas

  17. Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated topoisomerase I to promote genome stability.

    Directory of Open Access Journals (Sweden)

    Roland Steinacher

    Full Text Available The SUMO-dependent ubiquitin ligase Slx8 plays key roles in promoting genome stability, including the processing of trapped Topoisomerase I (Top1 cleavage complexes and removal of toxic SUMO conjugates. We show that it is the latter function that constitutes Slx8's primary role in fission yeast. The SUMO conjugates in question are formed by the SUMO ligase Pli1, which is necessary for limiting spontaneous homologous recombination when Top1 is present. Surprisingly there is no requirement for Pli1 to limit recombination in the vicinity of a replication fork blocked at the programmed barrier RTS1. Notably, once committed to Pli1-mediated SUMOylation Slx8 becomes essential for genotoxin resistance, limiting both spontaneous and RTS1 induced recombination, and promoting normal chromosome segregation. We show that Slx8 removes Pli1-dependent Top1-SUMO conjugates and in doing so helps to constrain recombination at RTS1. Overall our data highlight how SUMOylation and SUMO-dependent ubiquitylation by the Pli1-Slx8 axis contribute in different ways to maintain genome stability.

  18. Slx8 Removes Pli1-Dependent Protein-SUMO Conjugates Including SUMOylated Topoisomerase I to Promote Genome Stability

    Science.gov (United States)

    Steinacher, Roland; Osman, Fekret; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C.

    2013-01-01

    The SUMO-dependent ubiquitin ligase Slx8 plays key roles in promoting genome stability, including the processing of trapped Topoisomerase I (Top1) cleavage complexes and removal of toxic SUMO conjugates. We show that it is the latter function that constitutes Slx8's primary role in fission yeast. The SUMO conjugates in question are formed by the SUMO ligase Pli1, which is necessary for limiting spontaneous homologous recombination when Top1 is present. Surprisingly there is no requirement for Pli1 to limit recombination in the vicinity of a replication fork blocked at the programmed barrier RTS1. Notably, once committed to Pli1-mediated SUMOylation Slx8 becomes essential for genotoxin resistance, limiting both spontaneous and RTS1 induced recombination, and promoting normal chromosome segregation. We show that Slx8 removes Pli1-dependent Top1-SUMO conjugates and in doing so helps to constrain recombination at RTS1. Overall our data highlight how SUMOylation and SUMO-dependent ubiquitylation by the Pli1-Slx8 axis contribute in different ways to maintain genome stability. PMID:23936535

  19. GenoMatrix: A Software Package for Pedigree-Based and Genomic Prediction Analyses on Complex Traits.

    Science.gov (United States)

    Nazarian, Alireza; Gezan, Salvador Alejandro

    2016-07-01

    Genomic and pedigree-based best linear unbiased prediction methodologies (G-BLUP and P-BLUP) have proven themselves efficient for partitioning the phenotypic variance of complex traits into its components, estimating the individuals' genetic merits, and predicting unobserved (or yet-to-be observed) phenotypes in many species and fields of study. The GenoMatrix software, presented here, is a user-friendly package to facilitate the process of using genome-wide marker data and parentage information for G-BLUP and P-BLUP analyses on complex traits. It provides users with a collection of applications which help them on a set of tasks from performing quality control on data to constructing and manipulating the genomic and pedigree-based relationship matrices and obtaining their inverses. Such matrices will be then used in downstream analyses by other statistical packages. The package also enables users to obtain predicted values for unobserved individuals based on the genetic values of observed related individuals. GenoMatrix is available to the research community as a Windows 64bit executable and can be downloaded free of charge at: http://compbio.ufl.edu/software/genomatrix/. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Genomic analyses of primitive, wild and cultivated citrus provide insights into asexual reproduction.

    Science.gov (United States)

    Wang, Xia; Xu, Yuantao; Zhang, Siqi; Cao, Li; Huang, Yue; Cheng, Junfeng; Wu, Guizhi; Tian, Shilin; Chen, Chunli; Liu, Yan; Yu, Huiwen; Yang, Xiaoming; Lan, Hong; Wang, Nan; Wang, Lun; Xu, Jidi; Jiang, Xiaolin; Xie, Zongzhou; Tan, Meilian; Larkin, Robert M; Chen, Ling-Ling; Ma, Bin-Guang; Ruan, Yijun; Deng, Xiuxin; Xu, Qiang

    2017-05-01

    The emergence of apomixis-the transition from sexual to asexual reproduction-is a prominent feature of modern citrus. Here we de novo sequenced and comprehensively studied the genomes of four representative citrus species. Additionally, we sequenced 100 accessions of primitive, wild and cultivated citrus. Comparative population analysis suggested that genomic regions harboring energy- and reproduction-associated genes are probably under selection in cultivated citrus. We also narrowed the genetic locus responsible for citrus polyembryony, a form of apomixis, to an 80-kb region containing 11 candidate genes. One of these, CitRWP, is expressed at higher levels in ovules of polyembryonic cultivars. We found a miniature inverted-repeat transposable element insertion in the promoter region of CitRWP that cosegregated with polyembryony. This study provides new insights into citrus apomixis and constitutes a promising resource for the mining of agriculturally important genes.

  1. Genome-wide analyses of recombination suggest that Giardia intestinalis assemblages represent different species.

    Science.gov (United States)

    Xu, Feifei; Jerlström-Hultqvist, Jon; Andersson, Jan O

    2012-10-01

    Giardia intestinalis is a major cause of waterborne enteric disease in humans. The species is divided into eight assemblages suggested to represent separate Giardia species based on host specificities and the genetic divergence of marker genes. We have investigated whether genome-wide recombination occurs between assemblages using the three available G. intestinalis genomes. First, the relative nonsynonymous substitution rates of the homologs were compared for 4,009 positional homologs. The vast majority of these comparisons indicate genetic isolation without interassemblage recombinations. Only a region of 6 kbp suggests genetic exchange between assemblages A and E, followed by gene conversion events. Second, recombination-detecting software fails to identify within-gene recombination between the different assemblages for most of the homologs. Our results indicate very low frequency of recombination between the syntenic core genes, suggesting that G. intestinalis assemblages are genetically isolated lineages and thus should be viewed as separated Giardia species.

  2. Comprehensive Comparative Genomic and Transcriptomic Analyses of the Legume Genes Controlling the Nodulation Process.

    Science.gov (United States)

    Qiao, Zhenzhen; Pingault, Lise; Nourbakhsh-Rey, Mehrnoush; Libault, Marc

    2016-01-01

    Nitrogen is one of the most essential plant nutrients and one of the major factors limiting crop productivity. Having the goal to perform a more sustainable agriculture, there is a need to maximize biological nitrogen fixation, a feature of legumes. To enhance our understanding of the molecular mechanisms controlling the interaction between legumes and rhizobia, the symbiotic partner fixing and assimilating the atmospheric nitrogen for the plant, researchers took advantage of genetic and genomic resources developed across different legume models (e.g., Medicago truncatula, Lotus japonicus, Glycine max, and Phaseolus vulgaris) to identify key regulatory protein coding genes of the nodulation process. In this study, we are presenting the results of a comprehensive comparative genomic analysis to highlight orthologous and paralogous relationships between the legume genes controlling nodulation. Mining large transcriptomic datasets, we also identified several orthologous and paralogous genes characterized by the induction of their expression during nodulation across legume plant species. This comprehensive study prompts new insights into the evolution of the nodulation process in legume plant and will benefit the scientific community interested in the transfer of functional genomic information between species.

  3. Metabolic model for the filamentous ‘Candidatus Microthrix parvicella' based on genomic and metagenomic analyses

    Science.gov (United States)

    Jon McIlroy, Simon; Kristiansen, Rikke; Albertsen, Mads; Michael Karst, Søren; Rossetti, Simona; Lund Nielsen, Jeppe; Tandoi, Valter; James Seviour, Robert; Nielsen, Per Halkjær

    2013-01-01

    ‘Candidatus Microthrix parvicella' is a lipid-accumulating, filamentous bacterium so far found only in activated sludge wastewater treatment plants, where it is a common causative agent of sludge separation problems. Despite attracting considerable interest, its detailed physiology is still unclear. In this study, the genome of the RN1 strain was sequenced and annotated, which facilitated the construction of a theoretical metabolic model based on available in situ and axenic experimental data. This model proposes that under anaerobic conditions, this organism accumulates preferentially long-chain fatty acids as triacylglycerols. Utilisation of trehalose and/or polyphosphate stores or partial oxidation of long-chain fatty acids may supply the energy required for anaerobic lipid uptake and storage. Comparing the genome sequence of this isolate with metagenomes from two full-scale wastewater treatment plants with enhanced biological phosphorus removal reveals high similarity, with few metabolic differences between the axenic and the dominant community ‘Ca. M. parvicella' strains. Hence, the metabolic model presented in this paper could be considered generally applicable to strains in full-scale treatment systems. The genomic information obtained here will provide the basis for future research into in situ gene expression and regulation. Such information will give substantial insight into the ecophysiology of this unusual and biotechnologically important filamentous bacterium. PMID:23446830

  4. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

    Science.gov (United States)

    Hoffmann, Thomas J; Ehret, Georg B; Nandakumar, Priyanka; Ranatunga, Dilrini; Schaefer, Catherine; Kwok, Pui-Yan; Iribarren, Carlos; Chakravarti, Aravinda; Risch, Neil

    2017-01-01

    Longitudinal electronic health records on 99,785 Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort individuals provided 1,342,814 systolic and diastolic blood pressure measurements for a genome-wide association study on long-term average systolic, diastolic, and pulse pressure. We identified 39 new loci among 75 genome-wide significant loci (P ≤ 5 × 10(-8)), with most replicating in the combined International Consortium for Blood Pressure (ICBP; n = 69,396) and UK Biobank (UKB; n = 152,081) studies. Combining GERA with ICBP yielded 36 additional new loci, with most replicating in UKB. Combining all three studies (n = 321,262) yielded 241 additional genome-wide significant loci, although no replication sample was available for these. All associated loci explained 2.9%, 2.5%, and 3.1% of variation in systolic, diastolic, and pulse pressure, respectively, in GERA non-Hispanic whites. Using multiple blood pressure measurements in GERA doubled the variance explained. A normalized risk score was associated with time to onset of hypertension (hazards ratio = 1.18, P = 8.2 × 10(-45)). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery.

  5. UniPrimer: A Web-Based Primer Design Tool for Comparative Analyses of Primate Genomes

    Directory of Open Access Journals (Sweden)

    Nomin Batnyam

    2012-01-01

    Full Text Available Whole genome sequences of various primates have been released due to advanced DNA-sequencing technology. A combination of computational data mining and the polymerase chain reaction (PCR assay to validate the data is an excellent method for conducting comparative genomics. Thus, designing primers for PCR is an essential procedure for a comparative analysis of primate genomes. Here, we developed and introduced UniPrimer for use in those studies. UniPrimer is a web-based tool that designs PCR- and DNA-sequencing primers. It compares the sequences from six different primates (human, chimpanzee, gorilla, orangutan, gibbon, and rhesus macaque and designs primers on the conserved region across species. UniPrimer is linked to RepeatMasker, Primer3Plus, and OligoCalc softwares to produce primers with high accuracy and UCSC In-Silico PCR to confirm whether the designed primers work. To test the performance of UniPrimer, we designed primers on sample sequences using UniPrimer and manually designed primers for the same sequences. The comparison of the two processes showed that UniPrimer was more effective than manual work in terms of saving time and reducing errors.

  6. Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

  7. Genome, Transcriptome, and Functional Analyses of Penicillium expansum Provide New Insights Into Secondary Metabolism and Pathogenicity.

    Science.gov (United States)

    Ballester, Ana-Rosa; Marcet-Houben, Marina; Levin, Elena; Sela, Noa; Selma-Lázaro, Cristina; Carmona, Lourdes; Wisniewski, Michael; Droby, Samir; González-Candelas, Luis; Gabaldón, Toni

    2015-03-01

    The relationship between secondary metabolism and infection in pathogenic fungi has remained largely elusive. The genus Penicillium comprises a group of plant pathogens with varying host specificities and with the ability to produce a wide array of secondary metabolites. The genomes of three Penicillium expansum strains, the main postharvest pathogen of pome fruit, and one Pencillium italicum strain, a postharvest pathogen of citrus fruit, were sequenced and compared with 24 other fungal species. A genomic analysis of gene clusters responsible for the production of secondary metabolites was performed. Putative virulence factors in P. expansum were identified by means of a transcriptomic analysis of apple fruits during the course of infection. Despite a major genome contraction, P. expansum is the Penicillium species with the largest potential for the production of secondary metabolites. Results using knockout mutants clearly demonstrated that neither patulin nor citrinin are required by P. expansum to successfully infect apples. Li et al. ( MPMI-12-14-0398-FI ) reported similar results and conclusions in their recently accepted paper.

  8. Studies and analyses of the management of scientific research and development, including implementation and application at NASA centers

    Science.gov (United States)

    Rubenstein, A. H.

    1975-01-01

    Summary results obtained through the Program of Research on the Management of Research and Development (POMRAD) were presented. The nature of the overall program and the specific projects undertaken were described. Statistical data is also given concerning the papers, publications, people, and major program areas associated with the program. The actual list of papers, names of doctoral and masters theses, and other details of the program are included as appendices.

  9. The Mitochondrial Genomes of Aquila fasciata and Buteo lagopus (Aves, Accipitriformes: Sequence, Structure and Phylogenetic Analyses.

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    Lan Jiang

    Full Text Available The family Accipitridae is one of the largest groups of non-passerine birds, including 68 genera and 243 species globally distributed. In the present study, we determined the complete mitochondrial sequences of two species of accipitrid, namely Aquila fasciata and Buteo lagopus, and conducted a comparative mitogenome analysis across the family. The mitogenome length of A. fasciata and B. lagopus are 18,513 and 18,559 bp with an A + T content of 54.2% and 55.0%, respectively. For both the two accipitrid birds mtDNAs, obvious positive AT-skew and negative GC-skew biases were detected for all 12 PCGs encoded by the H strand, whereas the reverse was found in MT-ND6 encoded by the L strand. One extra nucleotide'C'is present at the position 174 of MT-ND3 gene of A. fasciata, which is not observed at that of B. lagopus. Six conserved sequence boxes in the Domain II, named boxes F, E, D, C, CSBa, and CSBb, respectively, were recognized in the CRs of A. fasciata and B. lagopus. Rates and patterns of mitochondrial gene evolution within Accipitridae were also estimated. The highest dN/dS was detected for the MT-ATP8 gene (0.32493 among Accipitridae, while the lowest for the MT-CO1 gene (0.01415. Mitophylogenetic analysis supported the robust monophyly of Accipitriformes, and Cathartidae was basal to the balance of the order. Moreover, we performed phylogenetic analyses using two other data sets (two mitochondrial loci, and combined nuclear and mitochondrial loci. Our results indicate that the subfamily Aquilinae and all currently polytypic genera of this subfamily are monophyletic. These two novel mtDNA data will be useful in refining the phylogenetic relationships and evolutionary processes of Accipitriformes.

  10. The Mitochondrial Genomes of Aquila fasciata and Buteo lagopus (Aves, Accipitriformes): Sequence, Structure and Phylogenetic Analyses.

    Science.gov (United States)

    Jiang, Lan; Chen, Juan; Wang, Ping; Ren, Qiongqiong; Yuan, Jian; Qian, Chaoju; Hua, Xinghong; Guo, Zhichun; Zhang, Lei; Yang, Jianke; Wang, Ying; Zhang, Qin; Ding, Hengwu; Bi, De; Zhang, Zongmeng; Wang, Qingqing; Chen, Dongsheng; Kan, Xianzhao

    2015-01-01

    The family Accipitridae is one of the largest groups of non-passerine birds, including 68 genera and 243 species globally distributed. In the present study, we determined the complete mitochondrial sequences of two species of accipitrid, namely Aquila fasciata and Buteo lagopus, and conducted a comparative mitogenome analysis across the family. The mitogenome length of A. fasciata and B. lagopus are 18,513 and 18,559 bp with an A + T content of 54.2% and 55.0%, respectively. For both the two accipitrid birds mtDNAs, obvious positive AT-skew and negative GC-skew biases were detected for all 12 PCGs encoded by the H strand, whereas the reverse was found in MT-ND6 encoded by the L strand. One extra nucleotide'C'is present at the position 174 of MT-ND3 gene of A. fasciata, which is not observed at that of B. lagopus. Six conserved sequence boxes in the Domain II, named boxes F, E, D, C, CSBa, and CSBb, respectively, were recognized in the CRs of A. fasciata and B. lagopus. Rates and patterns of mitochondrial gene evolution within Accipitridae were also estimated. The highest dN/dS was detected for the MT-ATP8 gene (0.32493) among Accipitridae, while the lowest for the MT-CO1 gene (0.01415). Mitophylogenetic analysis supported the robust monophyly of Accipitriformes, and Cathartidae was basal to the balance of the order. Moreover, we performed phylogenetic analyses using two other data sets (two mitochondrial loci, and combined nuclear and mitochondrial loci). Our results indicate that the subfamily Aquilinae and all currently polytypic genera of this subfamily are monophyletic. These two novel mtDNA data will be useful in refining the phylogenetic relationships and evolutionary processes of Accipitriformes.

  11. Classification and regression tree (CART analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria

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    Betsey Dexter Dyer

    2008-01-01

    Full Text Available Classification and regression tree (CART analysis was applied to genome-wide tetranucleotide frequencies (genomic signatures of 195 archaea and bacteria. Although genomic signatures have typically been used to classify evolutionary divergence, in this study, convergent evolution was the focus. Temperature optima for most of the organisms examined could be distinguished by CART analyses of tetranucleotide frequencies. This suggests that pervasive (nonlinear qualities of genomes may reflect certain environmental conditions (such as temperature in which those genomes evolved. The predominant use of GAGA and AGGA as the discriminating tetramers in CART models suggests that purine-loading and codon biases of thermophiles may explain some of the results.

  12. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

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    Xiao-Jin Hou

    Full Text Available MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB. Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  13. Initial Evidence for Adaptive Selection on the NADH Subunit Two of Freshwater Dolphins by Analyses of Mitochondrial Genomes

    Science.gov (United States)

    Caballero, Susana; Duchêne, Sebastian; Garavito, Manuel F.; Slikas, Beth; Baker, C. Scott

    2015-01-01

    A small number of cetaceans have adapted to an entirely freshwater environment, having colonized rivers in Asia and South America from an ancestral origin in the marine environment. This includes the ‘river dolphins’, early divergence from the odontocete lineage, and two species of true dolphins (Family Delphinidae). Successful adaptation to the freshwater environment may have required increased demands in energy involved in processes such as the mitochondrial osmotic balance. For this reason, riverine odontocetes provide a compelling natural experiment in adaptation of mammals from marine to freshwater habitats. Here we present initial evidence of positive selection in the NADH dehydrogenase subunit 2 of riverine odontocetes by analyses of full mitochondrial genomes, using tests of selection and protein structure modeling. The codon model with highest statistical support corresponds to three discrete categories for amino acid sites, those under positive, neutral, and purifying selection. With this model we found positive selection at site 297 of the NADH dehydrogenase subunit 2 (dN/dS>1.0,) leading to a substitution of an Ala or Val from the ancestral state of Thr. A phylogenetic reconstruction of 27 cetacean mitogenomes showed that an Ala substitution has evolved at least four times in cetaceans, once or more in the three ‘river dolphins’ (Families Pontoporidae, Lipotidae and Inidae), once in the riverine Sotalia fluviatilis (but not in its marine sister taxa), once in the riverine Orcaella brevirostris from the Mekong River (but not in its marine sister taxa) and once in two other related marine dolphins. We located the position of this amino acid substitution in an alpha-helix channel in the trans-membrane domain in both the E. coli structure and Sotalia fluviatilis model. In E. coli this position is located in a helix implicated in a proton translocation channel of respiratory complex 1 and may have a similar role in the NADH dehydrogenases of

  14. Initial Evidence for Adaptive Selection on the NADH Subunit Two of Freshwater Dolphins by Analyses of Mitochondrial Genomes.

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    Susana Caballero

    Full Text Available A small number of cetaceans have adapted to an entirely freshwater environment, having colonized rivers in Asia and South America from an ancestral origin in the marine environment. This includes the 'river dolphins', early divergence from the odontocete lineage, and two species of true dolphins (Family Delphinidae. Successful adaptation to the freshwater environment may have required increased demands in energy involved in processes such as the mitochondrial osmotic balance. For this reason, riverine odontocetes provide a compelling natural experiment in adaptation of mammals from marine to freshwater habitats. Here we present initial evidence of positive selection in the NADH dehydrogenase subunit 2 of riverine odontocetes by analyses of full mitochondrial genomes, using tests of selection and protein structure modeling. The codon model with highest statistical support corresponds to three discrete categories for amino acid sites, those under positive, neutral, and purifying selection. With this model we found positive selection at site 297 of the NADH dehydrogenase subunit 2 (dN/dS>1.0, leading to a substitution of an Ala or Val from the ancestral state of Thr. A phylogenetic reconstruction of 27 cetacean mitogenomes showed that an Ala substitution has evolved at least four times in cetaceans, once or more in the three 'river dolphins' (Families Pontoporidae, Lipotidae and Inidae, once in the riverine Sotalia fluviatilis (but not in its marine sister taxa, once in the riverine Orcaella brevirostris from the Mekong River (but not in its marine sister taxa and once in two other related marine dolphins. We located the position of this amino acid substitution in an alpha-helix channel in the trans-membrane domain in both the E. coli structure and Sotalia fluviatilis model. In E. coli this position is located in a helix implicated in a proton translocation channel of respiratory complex 1 and may have a similar role in the NADH dehydrogenases of

  15. Integrative genomics analyses reveal molecularly distinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion.

    Science.gov (United States)

    Mosca, Laura; Fabris, Sonia; Lionetti, Marta; Todoerti, Katia; Agnelli, Luca; Morabito, Fortunato; Cutrona, Giovanna; Andronache, Adrian; Matis, Serena; Ferrari, Francesco; Gentile, Massimo; Spriano, Mauro; Callea, Vincenzo; Festini, Gianluca; Molica, Stefano; Deliliers, Giorgio Lambertenghi; Bicciato, Silvio; Ferrarini, Manlio; Neri, Antonino

    2010-12-01

    Chromosome 13q14 deletion occurs in a substantial number of chronic lymphocytic leukemia (CLL) patients and it is believed to play a pathogenetic role. The exact mechanisms involved in this lesion have not yet been fully elucidated because of its heterogeneity and the imprecise knowledge of the implicated genes. This study was addressed to further contribute to the molecular definition of this lesion in CLL. We applied single-nucleotide polymorphism (SNP)-array technology and gene expression profiling data to investigate the 13q14 deletion occurring in a panel of 100 untreated, early-stage (Binet A) patients representative of the major genetics, molecular, and biological features of the disease. Concordantly with FISH analysis, SNP arrays identified 44 patients with del(13)(q14) including 11 cases with a biallelic deletion. The shorter monoallelic deletion was 635-kb long. The loss of the miR-15a/16-1 cluster occurred in all del(13)(q14) cases except in 2 patients with a monoallelic deletion, who retained both copies. MiR-15a/16 expression was significantly downregulated only in patients with the biallelic loss of the miRNA cluster compared to 13q normal cases. Finally, the natural grouping of SNP profiles by nonnegative matrix factorization algorithm showed that patients could be classified into 2 separate clusters, mainly characterized by short/biallelic versus wide/monoallelic 13q14 deletions. Supervised analyses of expression data showed that specific transcriptional profiles are correlated with these 2 genomic subgroups. Overall, our data highlight the presence of 2 distinct molecular types of 13q14 deletions, which may be of clinical relevance in CLL. ©2010 AACR.

  16. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Science.gov (United States)

    Hou, Xiao-Jin; Li, Si-Bei; Liu, Sheng-Rui; Hu, Chun-Gen; Zhang, Jin-Zhi

    2014-01-01

    MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB) family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB). Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  17. Genome-wide gene expression profile analyses identify CTTN as a potential prognostic marker in esophageal cancer.

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    Pei Lu

    Full Text Available AIM: Esophageal squamous cell carcinoma (ESCC is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. METHODS: We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR, tissue microarrays (TMAs and immunohistochemistry (IHC staining. RESULTS: Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤-1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26 and two underexpressed (HMGCS2 and SORBS2 were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN was observed in 126/198 (63.6% of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000, pathologic stage (P = 0.000 and poor survival (P<0.001 of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05. CONCLUSION: Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets.

  18. Combined genomic and structural analyses of a cultured magnetotactic bacterium reveals its niche adaptation to a dynamic environment

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    Ana Carolina Vieira Araujo

    2016-10-01

    Full Text Available Abstract Background Magnetotactic bacteria (MTB are a unique group of prokaryotes that have a potentially high impact on global geochemical cycling of significant primary elements because of their metabolic plasticity and the ability to biomineralize iron-rich magnetic particles called magnetosomes. Understanding the genetic composition of the few cultivated MTB along with the unique morphological features of this group of bacteria may provide an important framework for discerning their potential biogeochemical roles in natural environments. Results Genomic and ultrastructural analyses were combined to characterize the cultivated magnetotactic coccus Magnetofaba australis strain IT-1. Cells of this species synthesize a single chain of elongated, cuboctahedral magnetite (Fe3O4 magnetosomes that cause them to align along magnetic field lines while they swim being propelled by two bundles of flagella at velocities up to 300 μm s−1. High-speed microscopy imaging showed the cells move in a straight line rather than in the helical trajectory described for other magnetotactic cocci. Specific genes within the genome of Mf. australis strain IT-1 suggest the strain is capable of nitrogen fixation, sulfur reduction and oxidation, synthesis of intracellular polyphosphate granules and transporting iron with low and high affinity. Mf. australis strain IT-1 and Magnetococcus marinus strain MC-1 are closely related phylogenetically although similarity values between their homologous proteins are not very high. Conclusion Mf. australis strain IT-1 inhabits a constantly changing environment and its complete genome sequence reveals a great metabolic plasticity to deal with these changes. Aside from its chemoautotrophic and chemoheterotrophic metabolism, genomic data indicate the cells are capable of nitrogen fixation, possess high and low affinity iron transporters, and might be capable of reducing and oxidizing a number of sulfur compounds. The relatively

  19. Genome-wide association analyses for fatty acid composition in porcine muscle and abdominal fat tissues.

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    Bin Yang

    Full Text Available Fatty acid composition is an important phenotypic trait in pigs as it affects nutritional, technical and sensory quality of pork. Here, we reported a genome-wide association study (GWAS for fatty acid composition in the longissimus muscle and abdominal fat tissues of 591 White Duroc×Erhualian F2 animals and in muscle samples of 282 Chinese Sutai pigs. A total of 46 loci surpassing the suggestive significance level were identified on 15 pig chromosomes (SSC for 12 fatty acids, revealing the complex genetic architecture of fatty acid composition in pigs. Of the 46 loci, 15 on SSC5, 7, 14 and 16 reached the genome-wide significance level. The two most significant SNPs were ss131535508 (P = 2.48×10(-25 at 41.39 Mb on SSC16 for C20∶0 in abdominal fat and ss478935891 (P = 3.29×10(-13 at 121.31 Mb on SSC14 for muscle C18∶0. A meta-analysis of GWAS identified 4 novel loci and enhanced the association strength at 6 loci compared to those evidenced in a single population, suggesting the presence of common underlying variants. The longissimus muscle and abdominal fat showed consistent association profiles at most of the identified loci and distinct association signals at several loci. All loci have specific effects on fatty acid composition, except for two loci on SSC4 and SSC7 affecting multiple fatness traits. Several promising candidate genes were found in the neighboring regions of the lead SNPs at the genome-wide significant loci, such as SCD for C18∶0 and C16∶1 on SSC14 and ELOVL7 for C20∶0 on SSC16. The findings provide insights into the molecular basis of fatty acid composition in pigs, and would benefit the final identification of the underlying mutations.

  20. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

    Science.gov (United States)

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Xu, Chun; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana; Lee, Annette T; Mason, Andrew L; Myers, Robert P; Peltekian, Kevork M; Ghent, Cameron N; Bernuzzi, Francesca; Zuin, Massimo; Rosina, Floriano; Borghesio, Elisabetta; Floreani, Annarosa; Lazzari, Roberta; Niro, Grazia; Andriulli, Angelo; Muratori, Luigi; Muratori, Paolo; Almasio, Piero L; Andreone, Pietro; Margotti, Marzia; Brunetto, Maurizia; Coco, Barbara; Alvaro, Domenico; Bragazzi, Maria C; Marra, Fabio; Pisano, Alessandro; Rigamonti, Cristina; Colombo, Massimo; Marzioni, Marco; Benedetti, Antonio; Fabris, Luca; Strazzabosco, Mario; Portincasa, Piero; Palmieri, Vincenzo O; Tiribelli, Claudio; Croce, Lory; Bruno, Savino; Rossi, Sonia; Vinci, Maria; Prisco, Cleofe; Mattalia, Alberto; Toniutto, Pierluigi; Picciotto, Antonio; Galli, Andrea; Ferrari, Carlo; Colombo, Silvia; Casella, Giovanni; Morini, Lorenzo; Caporaso, Nicola; Colli, Agostino; Spinzi, Giancarlo; Montanari, Renzo; Gregersen, Peter K; Heathcote, E Jenny; Hirschfield, Gideon M; Siminovitch, Katherine A; Amos, Christopher I; Gershwin, M Eric; Seldin, Michael F

    2011-01-01

    A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38). PMID:20639880

  1. Genome-wide transcriptome analyses of silicon metabolism in Phaeodactylum tricornutum reveal the multilevel regulation of silicic acid transporters.

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    Guillaume Sapriel

    Full Text Available BACKGROUND: Diatoms are largely responsible for production of biogenic silica in the global ocean. However, in surface seawater, Si(OH(4 can be a major limiting factor for diatom productivity. Analyzing at the global scale the genes networks involved in Si transport and metabolism is critical in order to elucidate Si biomineralization, and to understand diatoms contribution to biogeochemical cycles. METHODOLOGY/PRINCIPAL FINDINGS: Using whole genome expression analyses we evaluated the transcriptional response to Si availability for the model species Phaeodactylum tricornutum. Among the differentially regulated genes we found genes involved in glutamine-nitrogen pathways, encoding putative extracellular matrix components, or involved in iron regulation. Some of these compounds may be good candidates for intracellular intermediates involved in silicic acid storage and/or intracellular transport, which are very important processes that remain mysterious in diatoms. Expression analyses and localization studies gave the first picture of the spatial distribution of a silicic acid transporter in a diatom model species, and support the existence of transcriptional and post-transcriptional regulations. CONCLUSIONS/SIGNIFICANCE: Our global analyses revealed that about one fourth of the differentially expressed genes are organized in clusters, underlying a possible evolution of P. tricornutum genome, and perhaps other pennate diatoms, toward a better optimization of its response to variable environmental stimuli. High fitness and adaptation of diatoms to various Si levels in marine environments might arise in part by global regulations from gene (expression level to genomic (organization in clusters, dosage compensation by gene duplication, and by post-transcriptional regulation and spatial distribution of SIT proteins.

  2. Genome-wide methylome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Li, Yongsheng; Camarillo, Cynthia; Xu, Juan; Arana, Tania Bedard; Xiao, Yun; Zhao, Zheng; Chen, Hong; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael A; Armas, Regina; Mendoza, Ricardo; Ontiveros, Alfonso; Nicolini, Humberto; Magaña, Alvaro Antonio Jerez; Rubin, Lewis P; Li, Xia; Xu, Chun

    2015-01-01

    Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3'-UTRs and 5'-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1) promoter CGIs hypermethylation with gene repression and (2) CGI 3'-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.

  3. Genome-Wide Methylome Analyses Reveal Novel Epigenetic Regulation Patterns in Schizophrenia and Bipolar Disorder

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    Yongsheng Li

    2015-01-01

    Full Text Available Schizophrenia (SZ and bipolar disorder (BP are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3′-UTRs and 5′-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1 promoter CGIs hypermethylation with gene repression and (2 CGI 3′-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.

  4. Combined genomics and experimental analyses of respiratory characteristics of Shewanella putrefaciens W3-18-1.

    Science.gov (United States)

    Qiu, Dongru; Wei, Hehong; Tu, Qichao; Yang, Yunfeng; Xie, Ming; Chen, Jingrong; Pinkerton, Mark H; Liang, Yili; He, Zhili; Zhou, Jizhong

    2013-09-01

    It has previously been shown that the Shewanella putrefaciens W3-18-1 strain produces remarkably high current in microbial fuel cells (MFCs) and can form magnetite at 0°C. To explore the underlying mechanisms, we developed a genetic manipulation method by deleting the restriction-modification system genes of the SGI1 (Salmonella genome island 1)-like prophage and analyzed the key genes involved in bacterial respiration. W3-18-1 has less respiratory flexibility than the well-characterized S. oneidensis MR-1 strain, as it possesses fewer cytochrome c genes and lacks the ability to oxidize sulfite or reduce dimethyl sulfoxide (DMSO) and timethylamine oxide (TMAO). W3-18-1 lacks the hydrogen-producing Fe-only hydrogenase, and the hydrogen-oxidizing Ni-Fe hydrogenase genes were split into two separate clusters. Two periplasmic nitrate reductases (NapDAGHB and NapDABC) were functionally redundant in anaerobic growth of W3-18-1 with nitrate as the electron acceptor, though napDABC was not regulated by Crp. Moreover, nitrate respiration started earlier in W3-18-1 than in MR-1 (with NapDAGHB only) under microoxic conditions. These results indicate that Shewanella putrefaciens W3-18-1 is well adapted to habitats with higher oxygen levels. Taken together, the results of this study provide valuable insights into bacterial genome evolution.

  5. Genome-Wide Methylome Analyses Reveal Novel Epigenetic Regulation Patterns in Schizophrenia and Bipolar Disorder

    Science.gov (United States)

    Li, Yongsheng; Camarillo, Cynthia; Xu, Juan; Arana, Tania Bedard; Xiao, Yun; Zhao, Zheng; Chen, Hong; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael A.; Armas, Regina; Mendoza, Ricardo; Ontiveros, Alfonso; Nicolini, Humberto; Jerez Magaña, Alvaro Antonio; Rubin, Lewis P.; Li, Xia; Xu, Chun

    2015-01-01

    Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3′-UTRs and 5′-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1) promoter CGIs hypermethylation with gene repression and (2) CGI 3′-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders. PMID:25734057

  6. Intrinsic disorder in Viral Proteins Genome-Linked: experimental and predictive analyses

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    Van Dorsselaer Alain

    2009-02-01

    Full Text Available Abstract Background VPgs are viral proteins linked to the 5' end of some viral genomes. Interactions between several VPgs and eukaryotic translation initiation factors eIF4Es are critical for plant infection. However, VPgs are not restricted to phytoviruses, being also involved in genome replication and protein translation of several animal viruses. To date, structural data are still limited to small picornaviral VPgs. Recently three phytoviral VPgs were shown to be natively unfolded proteins. Results In this paper, we report the bacterial expression, purification and biochemical characterization of two phytoviral VPgs, namely the VPgs of Rice yellow mottle virus (RYMV, genus Sobemovirus and Lettuce mosaic virus (LMV, genus Potyvirus. Using far-UV circular dichroism and size exclusion chromatography, we show that RYMV and LMV VPgs are predominantly or partly unstructured in solution, respectively. Using several disorder predictors, we show that both proteins are predicted to possess disordered regions. We next extend theses results to 14 VPgs representative of the viral diversity. Disordered regions were predicted in all VPg sequences whatever the genus and the family. Conclusion Based on these results, we propose that intrinsic disorder is a common feature of VPgs. The functional role of intrinsic disorder is discussed in light of the biological roles of VPgs.

  7. Genomic translational research: Paving the way to individualized cardiac functional analyses and personalized cardiology.

    Science.gov (United States)

    Pasipoularides, Ares

    2017-03-01

    For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice. Now on the horizon is an individualized, diverse patient-centered, approach to medical practice that encompasses the development of new, gene-based diagnostics and preventive medicine tactics, and offers the broadest range of personalized therapies based on pharmacogenetics. Over time, translation of genomic and high-tech approaches unquestionably will transform clinical practice in cardiology and medicine as a whole, with the adoption of new personalized medicine approaches and procedures. Clearly, future prospects far outweigh present accomplishments, which are best viewed as a promising start. It is now essential for pluridisciplinary health care providers to examine the drivers and barriers to the clinical adoption of this emerging revolutionary paradigm, in order to expedite the realization of its potential. So, we are not there yet, but we are definitely on our way.

  8. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    Science.gov (United States)

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.

  9. Genomic analyses of RH alleles to improve transfusion therapy in patients with sickle cell disease.

    Science.gov (United States)

    Reid, Marion E; Halter Hipsky, Christine; Hue-Roye, Kim; Hoppe, Carolyn

    2014-04-01

    Red cell (RBC) blood group alloimmunization remains a major problem in transfusion medicine. Patients with sickle cell disease (SCD) are at particularly high risk for developing alloantibodies to RBC antigens compared to other multiply transfused patient populations. Hemagglutination is the classical method used to test for blood group antigens, but depending on the typing methods and reagents used may result in discrepancies that preclude interpretation based on serologic reactivity alone. Molecular methods, including customized DNA microarrays, are increasingly used to complement serologic methods in predicting blood type. The purpose of this study was to determine the diversity and frequency of RH alleles in African Americans and to assess the performance of a DNA microarray for RH allele determination. Two sets of samples were tested: (i) individuals with known variant Rh types and (ii) randomly selected African American donors and patients with SCD. Standard hemagglutination tests were used to establish the Rh phenotype, and cDNA- and gDNA-based analyses (sequencing, PCR-RFLP, and customized RHD and RHCE microarrays were used to predict the genotype). In a total of 829 samples (1658 alleles), 72 different alleles (40 RHD and 32 RHCE) were identified, 22 of which are novel. DNA microarrays detected all nucleotides probed, allowing for characterization of over 900 alleles. High-throughput DNA testing platforms provide a means to test a relatively large number of donors and potentially prevent immunization by changing the way antigen-negative blood is provided to patients. Because of the high RH allelic diversity found in the African American population, determination of an accurate Rh phenotype often requires DNA testing, in conjunction with serologic testing. Allele-specific microarrays offer a means to perform high-throughput donor Rh typing and serve as a valuable adjunct to serologic methods to predict Rh type. Because DNA microarrays test for only a fixed

  10. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance.

    Directory of Open Access Journals (Sweden)

    Alessandro Orro

    Full Text Available In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and

  11. Streptococcal taxonomy based on genome sequence analyses [v1; ref status: indexed, http://f1000r.es/o1

    Directory of Open Access Journals (Sweden)

    Cristiane C Thompson

    2013-03-01

    Full Text Available The identification of the clinically relevant viridans streptococci group, at species level, is still problematic. The aim of this study was to extract taxonomic information from the complete genome sequences of 67 streptococci, comprising 19 species, by means of genomic analyses, multilocus sequence analysis (MLSA, average amino acid identity (AAI, genomic signatures, genome-to-genome distances (GGD and codon usage bias. We then attempted to determine the usefulness of these genomic tools for species identification in streptococci. Our results showed that MLSA, AAI and GGD analyses are robust markers to identify streptococci at the species level, for instance, S. pneumoniae, S. mitis, and S. oralis. A Streptococcus species can be defined as a group of strains that share ≥ 95% DNA similarity in MLSA and AAI, and > 70% DNA identity in GGD. This approach allows an advanced understanding of bacterial diversity.

  12. Genome Analysis of a Zygomycete Fungus Choanephora cucurbitarum Elucidates Necrotrophic Features Including Bacterial Genes Related to Plant Colonization

    Science.gov (United States)

    Min, Byoungnam; Park, Ji-Hyun; Park, Hongjae; Shin, Hyeon-Dong; Choi, In-Geol

    2017-01-01

    A zygomycete fungus, Choanephora cucurbitarum is a plant pathogen that causes blossom rot in cucurbits and other plants. Here we report the genome sequence of Choanephora cucurbitarum KUS-F28377 isolated from squash. The assembled genome has a size of 29.1 Mbp and 11,977 protein-coding genes. The genome analysis indicated that C. cucurbitarum may employ a plant pathogenic mechanism similar to that of bacterial plant pathogens. The genome contained 11 genes with a Streptomyces subtilisin inhibitor-like domain, which plays an important role in the defense against plant immunity. This domain has been found only in bacterial genomes. Carbohydrate active enzyme analysis detected 312 CAZymes in this genome where carbohydrate esterase family 6, rarely found in dikaryotic fungal genomes, was comparatively enriched. The comparative genome analysis showed that the genes related to sexual communication such as the biosynthesis of β-carotene and trisporic acid were conserved and diverged during the evolution of zygomycete genomes. Overall, these findings will help us to understand how zygomycetes are associated with plants. PMID:28091548

  13. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Luca, Gianina; Haba-Rubio, José; Dauvilliers, Yves

    2013-01-01

    diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women...... diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none...... of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset...

  14. Volatile terpenes from actinomycetes: a biosynthetic study correlating chemical analyses to genome data.

    Science.gov (United States)

    Rabe, Patrick; Citron, Christian A; Dickschat, Jeroen S

    2013-11-25

    The volatile terpenes of 24 actinomycetes whose genomes have been sequenced (or are currently being sequenced) were collected by use of a closed-loop stripping apparatus and identified by GC/MS. The analytical data were compared against a phylogenetic analysis of all 192 currently available sequences of bacterial terpene cyclases (excluding geosmin and 2-methylisoborneol synthases). In addition to the several groups of terpenes with known biosynthetic origin, selinadienes were identified as a large group of biosynthetically related sesquiterpenes that are produced by several streptomycetes. The detection of a large number of previously unrecognised side products of known terpene cyclases proved to be particularly important for an in depth understanding of biosynthetic pathways to known terpenes in actinomycetes. Interpretation of the chemical analytical data in the context of the phylogenetic tree of bacterial terpene cyclases pointed to the function of three new enzymes: (E)-β-caryophyllene synthase, selina-3,7(11)-diene synthase and aristolochene synthase.

  15. Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

    Directory of Open Access Journals (Sweden)

    Couturier Marie

    2012-02-01

    Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

  16. Defining window-boundaries for genomic analyses using smoothing spline techniques.

    Science.gov (United States)

    Beissinger, Timothy M; Rosa, Guilherme J M; Kaeppler, Shawn M; Gianola, Daniel; de Leon, Natalia

    2015-04-17

    High-density genomic data is often analyzed by combining information over windows of adjacent markers. Interpretation of data grouped in windows versus at individual locations may increase statistical power, simplify computation, reduce sampling noise, and reduce the total number of tests performed. However, use of adjacent marker information can result in over- or under-smoothing, undesirable window boundary specifications, or highly correlated test statistics. We introduce a method for defining windows based on statistically guided breakpoints in the data, as a foundation for the analysis of multiple adjacent data points. This method involves first fitting a cubic smoothing spline to the data and then identifying the inflection points of the fitted spline, which serve as the boundaries of adjacent windows. This technique does not require prior knowledge of linkage disequilibrium, and therefore can be applied to data collected from individual or pooled sequencing experiments. Moreover, in contrast to existing methods, an arbitrary choice of window size is not necessary, since these are determined empirically and allowed to vary along the genome. Simulations applying this method were performed to identify selection signatures from pooled sequencing FST data, for which allele frequencies were estimated from a pool of individuals. The relative ratio of true to false positives was twice that generated by existing techniques. A comparison of the approach to a previous study that involved pooled sequencing FST data from maize suggested that outlying windows were more clearly separated from their neighbors than when using a standard sliding window approach. We have developed a novel technique to identify window boundaries for subsequent analysis protocols. When applied to selection studies based on F ST data, this method provides a high discovery rate and minimizes false positives. The method is implemented in the R package GenWin, which is publicly available from CRAN.

  17. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.

    Science.gov (United States)

    Lux, Heike; Flammann, Heiko; Hafner, Mathias; Lux, Andreas

    2010-01-13

    The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's -1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

  18. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.

    Directory of Open Access Journals (Sweden)

    Heike Lux

    Full Text Available The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's -1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

  19. Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche.

    Directory of Open Access Journals (Sweden)

    Yao-Zhong Liu

    2009-03-01

    Full Text Available For females, menarche is a most significant physiological event. Age at menarche (AAM is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects--all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan, which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR q<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09 x 10(-3 and 4.37 x 10(-3, respectively, in the Chinese cohort and combined p values (obtained by Fisher's method of 5.19 x 10(-5 and 1.02 x 10(-4, respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2, a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM.

  20. Genomic DNA restriction endonuclease from Pasteurella multocida isolated from Indonesia, katha strain and reference strains and analysed by PFGE

    Directory of Open Access Journals (Sweden)

    Supar

    2003-10-01

    Full Text Available Pasteurella multocida strains are the causative disease agents of wide range of domestic and wild animals in Indonesia. The most important serotypes are associated with Hemorrhagic septicaemic (HS diseases in cattle and buffaloes, cholera in ducks and chickens. The HS disease associated with P. multocia in large ruminants in Indonesia is controled by killed whole cell vaccines produced by the use of P. multocida Katha strains. There is no discriminatory data of the molecular biology technique has been applied to investigate P. multocida isolates from different geographic locations in Indonesia. The purpose of this studies were to observe the genetic diversity among P. multocida isolated from various geograpic locations and compared with Katha vaccine strain and other reference strains. A total samples of 38 isolates and strains of P. multocida were analysed by means of pulsed-field gel electrophoresis (PFGE. Each sample was grown in nutrient broth, cells were separeted by centrifugation. Whole cell pellet was mixed with agarose and then prepared agarose plugs. The genomic DNA of each sample was digested in situ (plug with either restriction endonuclease of ApaI and/or BamHI. The digested genomic DNA of each sample was analysed by PFGE, the genomic DNA restricted profile of each sample was compared with others. The use of ApaI restriction endonuclease digestion and analysed by PFGE, demonstrated that 34 out of 38 P. multocia samples could be differentiated into 16 ApaI types, whereas based on the BamHI digestion of these samples were differentiated into 20 BamHI types. Genomic DNA restriction pattern of Indonesian P. multocida isolates originated from cattle and buffaloes associated with haemorrhagic septicaemic diseases demonstrated different pattern to those of vaccine Katha strain, poultry strains as well as the reference strains currenly kept at Balitvet Culture Collection (BCC unit. Two P. multocida isolates derived from ducks with cholera

  1. Origin and evolution of B chromosomes in the cichlid fish Astatotilapia latifasciata based on integrated genomic analyses.

    Science.gov (United States)

    Valente, Guilherme T; Conte, Matthew A; Fantinatti, Bruno E A; Cabral-de-Mello, Diogo C; Carvalho, Robson F; Vicari, Marcelo R; Kocher, Thomas D; Martins, Cesar

    2014-08-01

    Approximately 15% of eukaryotes contain supernumerary B chromosomes. When present, B chromosomes frequently represent as much as 5% of the genome. Despite thousands of reports describing the distribution of supernumeraries in various taxa, a comprehensive theory for the origin, maintenance, and evolution of B chromosomes has not emerged. Here, we sequence the complete genomes of individual cichlid fish (Astatotilapia latifasciata) with and without B chromosomes, as well as microdissected B chromosomes, to identify DNA sequences on the B. B sequences were further analyzed through quantitative polymerase chain reaction and in situ hybridization. We find that the B chromosome contains thousands of sequences duplicated from essentially every chromosome in the ancestral karyotype. Although most genes on the B chromosome are fragmented, a few are largely intact, and we detect evidence that at least three of them are transcriptionally active. We propose a model in which the B chromosome originated early in the evolutionary history of Lake Victoria cichlids from a small fragment of one autosome. DNA sequences originating from several autosomes, including protein-coding genes and transposable elements, subsequently inserted into this proto-B. We propose that intact B chromosome genes involved with microtubule organization, kinetochore structure, recombination and progression through the cell cycle may play a role in driving the transmission of the B chromosome. Furthermore, our work suggests that karyotyping is an essential step prior to genome sequencing to avoid problems in genome assembly and analytical biases created by the presence of high copy number sequences on the B chromosome.

  2. Genome Analyses of Icelandic Strains of Sulfolobus islandicus, Model Organisms for Genetic and Virus-Host Interaction Studies

    DEFF Research Database (Denmark)

    Guo, Li; Brügger, Kim; Liu, Chao;

    2011-01-01

    The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad h...... conjugative plasmids, which have integrated at a few tRNA genes lacking introns. This provides a possible rationale for the presence of the introns.......The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad...... in gene content and gene order occur. These include gene clusters involved in specific metabolic pathways, multiple copies of VapBC antitoxin-toxin gene pairs, and in strain HVE10/4, a 50-kb region rich in glycosyl transferase genes. The variable region also contains most of the insertion sequence (IS...

  3. Comparative sequence analyses of genome and transcriptome reveal novel transcripts and variants in the Asian elephant Elephas maximus

    Indian Academy of Sciences (India)

    Puli Chandramouli Reddy; Ishani Sinha; Ashwin Kelkar; Farhat Habib; Saurabh J Pradhan; Raman Sukumar; Sanjeev Galande

    2015-12-01

    The Asian elephant Elephas maximus and the African elephant Loxodonta africana that diverged 5-7 million years ago exhibit differences in their physiology, behaviour and morphology. A comparative genomics approach would be useful and necessary for evolutionary and functional genetic studies of elephants. We performed sequencing of E. maximus and map to L. africana at ∼ 15X coverage. Through comparative sequence analyses, we have identified Asian elephant specific homozygous, non-synonymous single nucleotide variants (SNVs) that map to 1514 protein coding genes, many of which are involved in olfaction. We also present the first report of a high-coverage transcriptome sequence in E. maximus from peripheral blood lymphocytes. We have identified 103 novel protein coding transcripts and 66-long non-coding (Inc)RNAs. We also report the presence of 181 protein domains unique to elephants when compared to other Afrotheria species. Each of these findings can be further investigated to gain a better understanding of functional differences unique to elephant species, as well as those unique to elephantids in comparison with other mammals. This work therefore provides a valuable resource to explore the immense research potential of comparative analyses of transcriptome and genome sequences in the Asian elephant.

  4. Comparative sequence analyses of genome and transcriptome reveal novel transcripts and variants in the Asian elephant Elephas maximus.

    Science.gov (United States)

    Reddy, Puli Chandramouli; Sinha, Ishani; Kelkar, Ashwin; Habib, Farhat; Pradhan, Saurabh J; Sukumar, Raman; Galande, Sanjeev

    2015-12-01

    The Asian elephant Elephas maximus and the African elephant Loxodonta africana that diverged 5-7 million years ago exhibit differences in their physiology, behaviour and morphology. A comparative genomics approach would be useful and necessary for evolutionary and functional genetic studies of elephants. We performed sequencing of E. maximus and map to L. africana at ~15X coverage. Through comparative sequence analyses, we have identified Asian elephant specific homozygous, non-synonymous single nucleotide variants (SNVs) that map to 1514 protein coding genes, many of which are involved in olfaction. We also present the first report of a high-coverage transcriptome sequence in E. maximus from peripheral blood lymphocytes. We have identified 103 novel protein coding transcripts and 66-long non-coding (lnc)RNAs. We also report the presence of 181 protein domains unique to elephants when compared to other Afrotheria species. Each of these findings can be further investigated to gain a better understanding of functional differences unique to elephant species, as well as those unique to elephantids in comparison with other mammals. This work therefore provides a valuable resource to explore the immense research potential of comparative analyses of transcriptome and genome sequences in the Asian elephant.

  5. Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp.

    Science.gov (United States)

    Chen, Chao; Liu, Zhiguang; Pan, Qi; Chen, Xiao; Wang, Huihua; Guo, Haikun; Liu, Shidong; Lu, Hongfeng; Tian, Shilin; Li, Ruiqiang; Shi, Wei

    2016-05-01

    Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies.

  6. Comparison of Genome-Wide Association Methods in Analyses of Admixed Populations with Complex Familial Relationships

    DEFF Research Database (Denmark)

    Kadri, Naveen; Guldbrandtsen, Bernt; Sørensen, Peter;

    2014-01-01

    ) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic......Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K...... corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree...

  7. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  8. Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood

    OpenAIRE

    Chan, Wing Keung; Rujkijyanont, Piya; Neale, Geoffrey; Jie YANG; Bari, Rafijul; Gupta, Neha Das; Holladay, Martha; Rooney, Barbara; Leung, Wing

    2013-01-01

    Killer-cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells have been linked to a wide spectrum of health conditions such as chronic infections, autoimmune diseases, pregnancy complications, cancers, and transplant failures. A small subset of effector memory T cells also expresses KIRs. Here, we use modern analytic tools including genome-wide and multiplex molecular, phenotypic, and functional assays to characterize the KIR+ T cells in human blood. We find that KIR+ T cells ...

  9. Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

    Science.gov (United States)

    Zhang, Lei; Choi, Hyung Jin; Estrada, Karol; Leo, Paul J; Li, Jian; Pei, Yu-Fang; Zhang, Yinping; Lin, Yong; Shen, Hui; Liu, Yao-Zhong; Liu, Yongjun; Zhao, Yingchun; Zhang, Ji-Gang; Tian, Qing; Wang, Yu-ping; Han, Yingying; Ran, Shu; Hai, Rong; Zhu, Xue-Zhen; Wu, Shuyan; Yan, Han; Liu, Xiaogang; Yang, Tie-Lin; Guo, Yan; Zhang, Feng; Guo, Yan-fang; Chen, Yuan; Chen, Xiangding; Tan, Lijun; Zhang, Lishu; Deng, Fei-Yan; Deng, Hongyi; Rivadeneira, Fernando; Duncan, Emma L; Lee, Jong Young; Han, Bok Ghee; Cho, Nam H; Nicholson, Geoffrey C; McCloskey, Eugene; Eastell, Richard; Prince, Richard L; Eisman, John A; Jones, Graeme; Reid, Ian R; Sambrook, Philip N; Dennison, Elaine M; Danoy, Patrick; Yerges-Armstrong, Laura M; Streeten, Elizabeth A; Hu, Tian; Xiang, Shuanglin; Papasian, Christopher J; Brown, Matthew A; Shin, Chan Soo; Uitterlinden, André G; Deng, Hong-Wen

    2014-04-01

    Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

  10. Genomic and phylogenetic analyses of an adenovirus isolated from a corn snake (Elaphe guttata) imply a common origin with members of the proposed new genus Atadenovirus.

    Science.gov (United States)

    Farkas, Szilvia L; Benko, Mária; Elo, Péter; Ursu, Krisztina; Dán, Adám; Ahne, Winfried; Harrach, Balázs

    2002-10-01

    Approximately 60% of the genome of an adenovirus isolated from a corn snake (Elaphe guttata) was cloned and sequenced. The results of homology searches showed that the genes of the corn snake adenovirus (SnAdV-1) were closest to their counterparts in members of the recently proposed new genus ATADENOVIRUS: In phylogenetic analyses of the complete hexon and protease genes, SnAdV-1 indeed clustered together with the atadenoviruses. The characteristic features in the genome organization of SnAdV-1 included the presence of a gene homologous to that for protein p32K, the lack of structural proteins V and IX and the absence of homologues of the E1A and E3 regions. These characteristics are in accordance with the genus-defining markers of atadenoviruses. Comparison of the cleavage sites of the viral protease in core protein pVII also confirmed SnAdV-1 as a candidate member of the genus ATADENOVIRUS: Thus, the hypothesis on the possible reptilian origin of atadenoviruses (Harrach, Acta Veterinaria Hungarica 48, 484-490, 2000) seems to be supported. However, the base composition of DNA sequence (>18 kb) determined from the SnAdV-1 genome showed an equilibrated GC content of 51%, which is unusual for an atadenovirus.

  11. BioSMACK: a linux live CD for genome-wide association analyses.

    Science.gov (United States)

    Hong, Chang Bum; Kim, Young Jin; Moon, Sanghoon; Shin, Young-Ah; Go, Min Jin; Kim, Dong-Joon; Lee, Jong-Young; Cho, Yoon Shin

    2012-01-01

    Recent advances in high-throughput genotyping technologies have enabled us to conduct a genome-wide association study (GWAS) on a large cohort. However, analyzing millions of single nucleotide polymorphisms (SNPs) is still a difficult task for researchers conducting a GWAS. Several difficulties such as compatibilities and dependencies are often encountered by researchers using analytical tools, during the installation of software. This is a huge obstacle to any research institute without computing facilities and specialists. Therefore, a proper research environment is an urgent need for researchers working on GWAS. We developed BioSMACK to provide a research environment for GWAS that requires no configuration and is easy to use. BioSMACK is based on the Ubuntu Live CD that offers a complete Linux-based operating system environment without installation. Moreover, we provide users with a GWAS manual consisting of a series of guidelines for GWAS and useful examples. BioSMACK is freely available at http://ksnp.cdc. go.kr/biosmack.

  12. Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Mirjam Appel

    Full Text Available Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/ or sequences co-varied with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance-associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hair-like organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.

  13. Super-sparse principal component analyses for high-throughput genomic data

    Directory of Open Access Journals (Sweden)

    Lee Youngjo

    2010-06-01

    Full Text Available Abstract Background Principal component analysis (PCA has gained popularity as a method for the analysis of high-dimensional genomic data. However, it is often difficult to interpret the results because the principal components are linear combinations of all variables, and the coefficients (loadings are typically nonzero. These nonzero values also reflect poor estimation of the true vector loadings; for example, for gene expression data, biologically we expect only a portion of the genes to be expressed in any tissue, and an even smaller fraction to be involved in a particular process. Sparse PCA methods have recently been introduced for reducing the number of nonzero coefficients, but these existing methods are not satisfactory for high-dimensional data applications because they still give too many nonzero coefficients. Results Here we propose a new PCA method that uses two innovations to produce an extremely sparse loading vector: (i a random-effect model on the loadings that leads to an unbounded penalty at the origin and (ii shrinkage of the singular values obtained from the singular value decomposition of the data matrix. We develop a stable computing algorithm by modifying nonlinear iterative partial least square (NIPALS algorithm, and illustrate the method with an analysis of the NCI cancer dataset that contains 21,225 genes. Conclusions The new method has better performance than several existing methods, particularly in the estimation of the loading vectors.

  14. Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster.

    Science.gov (United States)

    Appel, Mirjam; Scholz, Claus-Jürgen; Müller, Tobias; Dittrich, Marcus; König, Christian; Bockstaller, Marie; Oguz, Tuba; Khalili, Afshin; Antwi-Adjei, Emmanuel; Schauer, Tamas; Margulies, Carla; Tanimoto, Hiromu; Yarali, Ayse

    2015-01-01

    Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/ or sequences co-varied with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance-associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hair-like organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.

  15. CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening.

    Science.gov (United States)

    Wang, Mingjun; Lamberth, Kasper; Harndahl, Mikkel; Røder, Gustav; Stryhn, Anette; Larsen, Mette V; Nielsen, Morten; Lundegaard, Claus; Tang, Sheila T; Dziegiel, Morten H; Rosenkvist, Jørgen; Pedersen, Anders E; Buus, Søren; Claesson, Mogens H; Lund, Ole

    2007-04-12

    The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.

  16. Genome-wide identification and expression analyses of cytochrome P450 genes in mulberry (Morus notabilis)

    Institute of Scientific and Technical Information of China (English)

    Bi Ma; Yiwei Luo; Ling Jia; Xiwu Qi; Qiwei Zeng; Zhonghuai Xiang; Ningjia He

    2014-01-01

    Cytochrome P450s play critical roles in the biosyn-thesis of physiological y important compounds in plants. These compounds often act as defense toxins to prevent herbivory. In the present study, a total of 174 P450 genes of mulberry (Morus notabilis C.K.Schn) were identified based on bioinfor-matics analyses. These mulberry P450 genes were divided into nine clans and 47 families and were found to be expressed in a tissue-preferential manner. These genes were compared to the P450 genes in Arabidopsis thaliana. Families CYP80, CYP92, CYP728, CYP733, CYP736, and CYP749 were found to exist in mulberry, and they may play important roles in the biosynthesis of mulberry secondary metabolites. Analyses of the functional and metabolic pathways of these genes indicated that mulberry P450 genes may participate in the metabolism of lipids, other secondary metabolites, xenobiotics, amino acids, cofactors, vitamins, terpenoids, and polyketides. These results provide a foundation for understanding of the structures and biological functions of mulberry P450 genes.

  17. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

    Directory of Open Access Journals (Sweden)

    Samuel E Jones

    2016-08-01

    Full Text Available Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8, including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12 and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10. The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8. For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16 and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9. Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05; undersleeping and BMI (rG = 0.147, P = 1x10-5 and oversleeping and BMI (rG = 0.097, P = 0.04, Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and

  18. Whole-genome analyses of the speciation events in the pathogenic Brucellae

    Energy Technology Data Exchange (ETDEWEB)

    Chain, P; Comerci, D; Tolmasky, M; Larimer, F; Malfatti, S; Vergez, L; Aguero, F; Land, M; Ugalde, R; Garcia, E

    2005-07-14

    Despite their high DNA identity and a proposal to group classical Brucella species as biovars of B. melitensis, the commonly recognized Brucella species can be distinguished by distinct biochemical and fatty acid characters as well as by a marked host range (e.g. B. suis for swine, B. melitensis for sheep and goats, B. abortus for cattle). Here we present the genome of B. abortus 2308, the virulent prototype biovar 1 strain, and its comparison to the two other human pathogenic Brucellae species and to the B. abortus field isolate 9-941. The global distribution of pseudogenes, deletions and insertions support previous indications that B. abortus and B. melitensis share a common ancestor that diverged from B. suis. With the exception of a dozen genes, the genetic complement of both B. abortus strains is identical, whereas the three species differ in gene content and pseudogenes. The pattern of species-specific gene inactivations affecting transcriptional regulators and outer membrane proteins suggest that these inactivations may play an important role in the establishment of host-specificity and may have been a primary driver of speciation in the Brucellae. Despite being non-motile, the Brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures, and may contribute to differences in host-specificity and virulence. Metabolic changes such as the lack of complete metabolic pathways for the synthesis of numerous compounds (e.g. glycogen, biotin, NAD, and choline) are consistent with adaptation of Brucellae to an intracellular lifestyle.

  19. Genomic and evolutionary analyses of Tango transposons in Aedes aegypti, Anopheles gambiae and other mosquito species.

    Science.gov (United States)

    Coy, M R; Tu, Z

    2007-08-01

    Tango is a transposon of the Tc1 family and was originally discovered in the African malaria mosquito, Anopheles gambiae. Here we report a systematic analysis of the genome sequence of the yellow fever mosquito, Aedes aegypti, which uncovered three distinct Tango transposons. We name the only An. gambiae Tango transposon AgTango1 and the three Ae. aegypti Tango elements AeTango1-3. Like AgTango1, AeTango1 and AeTango2 elements both have members that retain characteristics of autonomous elements such as intact open reading frames and terminal inverted repeats (TIRs). AeTango3 is a degenerate transposon with no full-length members. All full-length Tango transposons contain subterminal direct repeats within their TIRs. AgTango1 and AeTango1-3 form a single clade among other Tc1 transposons. Within this clade, AgTango1 and AeTango1 are closely related and share approximately 80% identity at the amino acid level, which exceeds the level of similarity of the majority of host genes in the two species. A survey of Tango in other mosquito species was carried out using degenerate PCR. Tango was isolated and sequenced in all members of the An. gambiae species complex, Aedes albopictus and Ochlerotatus atropalpus. Oc. atropalpus contains a rich diversity of Tango elements, while Tango elements in Ae. albopictus and the An. gambiae species complex all belong to Tango1. No Tango was detected in Culex pipiens quinquefasciatus, Anopheles stephensi, Anopheles dirus, Anopheles farauti or Anopheles albimanus using degenerate PCR. Bioinformatic searches of the Cx. p. quinquefasciatus (~10 x coverage) and An. stephensi (0.33 x coverage) databases also failed to uncover any Tango elements. Although other evolutionary scenarios cannot be ruled out, there are indications that Tango1 underwent horizontal transfer among divergent mosquito species.

  20. Comparative Genome Analyses of Streptococcus suis Isolates from Endocarditis Demonstrate Persistence of Dual Phenotypic Clones.

    Directory of Open Access Journals (Sweden)

    Mari Tohya

    Full Text Available Many bacterial species coexist in the same niche as heterogeneous clones with different phenotypes; however, understanding of infectious diseases by polyphenotypic bacteria is still limited. In the present study, encapsulation in isolates of the porcine pathogen Streptococcus suis from persistent endocarditis lesions was examined. Coexistence of both encapsulated and unencapsulated S. suis isolates was found in 26 out of 59 endocarditis samples. The isolates were serotype 2, and belonged to two different sequence types (STs, ST1 and ST28. The genomes of each of the 26 pairs of encapsulated and unencapsulated isolates from the 26 samples were sequenced. The data showed that each pair of isolates had one or more unique nonsynonymous mutations in the cps gene, and the encapsulated and unencapsulated isolates from the same samples were closest to each other. Pairwise comparisons of the sequences of cps genes in 7 pairs of encapsulated and unencapsulated isolates identified insertion/deletions (indels ranging from one to 104 bp in different cps genes of unencapsulated isolates. Capsule expression was restored in a subset of unencapsulated isolates by complementation in trans with cps expression vectors. Examination of gene content common to isolates indicated that mutation frequency was higher in ST28 pairs than in ST1 pairs. Genes within mobile genetic elements were mutation hot spots among ST28 isolates. Taken all together, our results demonstrate the coexistence of dual phenotype (encapsulated and unencapsulated bacterial clones and suggest that the dual phenotypes arose independently in each farm by means of spontaneous mutations in cps genes.

  1. Comparative genomic analyses reveal a lack of a substantial signature of host adaptation in Rhodococcus equi ('Prescottella equi').

    Science.gov (United States)

    Sangal, Vartul; Jones, Amanda L; Goodfellow, Michael; Sutcliffe, Iain C; Hoskisson, Paul A

    2014-08-01

    Rhodococcus equi ('Prescottella equi') is a pathogenic actinomycete primarily infecting horses but has emerged as an opportunistic human pathogen. We have sequenced the genome of the type strain of this species, R. equi strain C7(T) , and compared the genome with that of another foal isolate 103S and of a human isolate ATCC 33707. The R. equi strains are closely related to each other and yet distantly related to other rhodococci and Nocardia brasiliensis. The comparison of gene contents among R. equi strains revealed minor differences that could be associated with host adaptation from foals to humans, including the presence of a paa operon in the human isolate, which is potentially involved in pathogenesis. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  2. Genomic and in silico analyses of CRBN gene and thalidomide embryopathy in humans.

    Science.gov (United States)

    Vianna, Fernanda Sales Luiz; Kowalski, Thayne Woycinck; Tovo-Rodrigues, Luciana; Tagliani-Ribeiro, Alice; Godoy, Bibiane Armiliato; Fraga, Lucas Rosa; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia

    2016-12-01

    Thalidomide causes Thalidomide Embryopathy (TE), but is largely used to treat several conditions. Investigations with Cereblon, a thalidomide target protein encoded by CRBN gene, have helped to understand thalidomide therapeutic and teratogenic properties. We sequenced CRBN-thalidomide binding region in 38 TE individuals and 136 Brazilians without congenital anomalies, and performed in silico analyses. Eight variants were identified, seven intronic and one in 3'UTR. TE individuals had rare variants in higher frequency than the non-affected group (p=0.04). The genotype rs1620675 CC was related to neurological anomalies in TE individuals (p=0.004). Bioinformatics analysis suggested this genotype leads to potential alterations in splicing sites and binding to transcription factors. Comparison of the Cereblon-thalidomide binding domains in mammals demonstrated that CRBN is highly conserved across species. All the variants require evaluation in functional assays in order to understand their role in Cereblon-thalidomide binding and complex interactions that lead to TE.

  3. Unraveling the evolutionary history of the phosphoryl-transfer chain of the phosphoenolpyruvate:phosphotransferase system through phylogenetic analyses and genome context

    Directory of Open Access Journals (Sweden)

    Zúñiga Manuel

    2008-05-01

    Full Text Available Abstract Background The phosphoenolpyruvate phosphotransferase system (PTS plays a major role in sugar transport and in the regulation of essential physiological processes in many bacteria. The PTS couples solute transport to its phosphorylation at the expense of phosphoenolpyruvate (PEP and it consists of general cytoplasmic phosphoryl transfer proteins and specific enzyme II complexes which catalyze the uptake and phosphorylation of solutes. Previous studies have suggested that the evolution of the constituents of the enzyme II complexes has been driven largely by horizontal gene transfer whereas vertical inheritance has been prevalent in the general phosphoryl transfer proteins in some bacterial groups. The aim of this work is to test this hypothesis by studying the evolution of the phosphoryl transfer proteins of the PTS. Results We have analyzed the evolutionary history of the PTS phosphoryl transfer chain (PTS-ptc components in 222 complete genomes by combining phylogenetic methods and analysis of genomic context. Phylogenetic analyses alone were not conclusive for the deepest nodes but when complemented with analyses of genomic context and functional information, the main evolutionary trends of this system could be depicted. Conclusion The PTS-ptc evolved in bacteria after the divergence of early lineages such as Aquificales, Thermotogales and Thermus/Deinococcus. The subsequent evolutionary history of the PTS-ptc varied in different bacterial lineages: vertical inheritance and lineage-specific gene losses mainly explain the current situation in Actinobacteria and Firmicutes whereas horizontal gene transfer (HGT also played a major role in Proteobacteria. Most remarkably, we have identified a HGT event from Firmicutes or Fusobacteria to the last common ancestor of the Enterobacteriaceae, Pasteurellaceae, Shewanellaceae and Vibrionaceae. This transfer led to extensive changes in the metabolic and regulatory networks of these bacteria

  4. Subcellular localization of extracytoplasmic proteins in monoderm bacteria: rational secretomics-based strategy for genomic and proteomic analyses.

    Directory of Open Access Journals (Sweden)

    Sandra Renier

    Full Text Available Genome-scale prediction of subcellular localization (SCL is not only useful for inferring protein function but also for supporting proteomic data. In line with the secretome concept, a rational and original analytical strategy mimicking the secretion steps that determine ultimate SCL was developed for Gram-positive (monoderm bacteria. Based on the biology of protein secretion, a flowchart and decision trees were designed considering (i membrane targeting, (ii protein secretion systems, (iii membrane retention, and (iv cell-wall retention by domains or post-translocational modifications, as well as (v incorporation to cell-surface supramolecular structures. Using Listeria monocytogenes as a case study, results were compared with known data set from SCL predictors and experimental proteomics. While in good agreement with experimental extracytoplasmic fractions, the secretomics-based method outperforms other genomic analyses, which were simply not intended to be as inclusive. Compared to all other localization predictors, this method does not only supply a static snapshot of protein SCL but also offers the full picture of the secretion process dynamics: (i the protein routing is detailed, (ii the number of distinct SCL and protein categories is comprehensive, (iii the description of protein type and topology is provided, (iv the SCL is unambiguously differentiated from the protein category, and (v the multiple SCL and protein category are fully considered. In that sense, the secretomics-based method is much more than a SCL predictor. Besides a major step forward in genomics and proteomics of protein secretion, the secretomics-based method appears as a strategy of choice to generate in silico hypotheses for experimental testing.

  5. Genomic and transcriptomic resources for assassin flies including the complete genome sequence of Proctacanthus coquilletti (Insecta: Diptera: Asilidae and 16 representative transcriptomes

    Directory of Open Access Journals (Sweden)

    Rebecca B. Dikow

    2017-01-01

    Full Text Available A high-quality draft genome for Proctacanthus coquilletti (Insecta: Diptera: Asilidae is presented along with transcriptomes for 16 Diptera species from five families: Asilidae, Apioceridae, Bombyliidae, Mydidae, and Tabanidae. Genome sequencing reveals that P. coquilletti has a genome size of approximately 210 Mbp and remarkably low heterozygosity (0.47% and few repeats (15%. These characteristics helped produce a highly contiguous (N50 = 862 kbp assembly, particularly given that only a single 2 × 250 bp PCR-free Illumina library was sequenced. A phylogenomic hypothesis is presented based on thousands of putative orthologs across the 16 transcriptomes. Phylogenetic relationships support the sister group relationship of Apioceridae + Mydidae to Asilidae. A time-calibrated phylogeny is also presented, with seven fossil calibration points, which suggests an older age of the split among Apioceridae, Asilidae, and Mydidae (158 mya and Apioceridae and Mydidae (135 mya than proposed in the AToL FlyTree project. Future studies will be able to take advantage of the resources presented here in order to produce large scale phylogenomic and evolutionary studies of assassin fly phylogeny, life histories, or venom. The bioinformatics tools and workflow presented here will be useful to others wishing to generate de novo genomic resources in species-rich taxa without a closely-related reference genome.

  6. Genomic and transcriptomic resources for assassin flies including the complete genome sequence of Proctacanthus coquilletti (Insecta: Diptera: Asilidae) and 16 representative transcriptomes

    Science.gov (United States)

    Frandsen, Paul B.; Turcatel, Mauren

    2017-01-01

    A high-quality draft genome for Proctacanthus coquilletti (Insecta: Diptera: Asilidae) is presented along with transcriptomes for 16 Diptera species from five families: Asilidae, Apioceridae, Bombyliidae, Mydidae, and Tabanidae. Genome sequencing reveals that P. coquilletti has a genome size of approximately 210 Mbp and remarkably low heterozygosity (0.47%) and few repeats (15%). These characteristics helped produce a highly contiguous (N50 = 862 kbp) assembly, particularly given that only a single 2 × 250 bp PCR-free Illumina library was sequenced. A phylogenomic hypothesis is presented based on thousands of putative orthologs across the 16 transcriptomes. Phylogenetic relationships support the sister group relationship of Apioceridae + Mydidae to Asilidae. A time-calibrated phylogeny is also presented, with seven fossil calibration points, which suggests an older age of the split among Apioceridae, Asilidae, and Mydidae (158 mya) and Apioceridae and Mydidae (135 mya) than proposed in the AToL FlyTree project. Future studies will be able to take advantage of the resources presented here in order to produce large scale phylogenomic and evolutionary studies of assassin fly phylogeny, life histories, or venom. The bioinformatics tools and workflow presented here will be useful to others wishing to generate de novo genomic resources in species-rich taxa without a closely-related reference genome.

  7. Metabolomic and Functional Genomic Analyses Reveal Varietal Differences in Bioactive Compounds of Cooked Rice

    Science.gov (United States)

    Heuberger, Adam L.; Lewis, Matthew R.; Chen, Ming-Hsuan; Brick, Mark A.; Leach, Jan E.; Ryan, Elizabeth P.

    2010-01-01

    Emerging evidence supports that cooked rice (Oryza sativa L.) contains metabolites with biomedical activities, yet little is known about the genetic diversity that is responsible for metabolite variation and differences in health traits. Metabolites from ten diverse varieties of cooked rice were detected using ultra performance liquid chromatography coupled to mass spectrometry. A total of 3,097 compounds were detected, of which 25% differed among the ten varieties. Multivariate analyses of the metabolite profiles showed that the chemical diversity among the varieties cluster according to their defined subspecies classifications: indica, japonica, and aus. Metabolite-specific genetic diversity in rice was investigated by analyzing a collection of single nucleotide polymorphisms (SNPs) in genes from biochemical pathways of nutritional importance. Two classes of bioactive compounds, phenolics and vitamin E, contained nonsynonymous SNPs and SNPs in the 5′ and 3′ untranslated regions for genes in their biosynthesis pathways. Total phenolics and tocopherol concentrations were determined to examine the effect of the genetic diversity among the ten varieties. Per gram of cooked rice, total phenolics ranged from 113.7 to 392.6 µg (gallic acid equivalents), and total tocopherols ranged between 7.2 and 20.9 µg. The variation in the cooked rice metabolome and quantities of bioactive components supports that the SNP-based genetic diversity influenced nutritional components in rice, and that this approach may guide rice improvement strategies for plant and human health. PMID:20886119

  8. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci

    Science.gov (United States)

    Gelernter, J; Kranzler, HR; Sherva, R; Almasy, L; Koesterer, R; Smith, AH; Anton, R; Preuss, UW; Ridinger, M; Rujescu, D; Wodarz, N; Zill, P; Zhao, H; Farrer, LA

    2014-01-01

    We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus, showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P = 1.17 × 10−31; AAs: Arg369Cys, P = 6.33 × 10−17) and ADH1C in AAs (Thr151Thr, P = 4.94 × 10−10), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P = 2.63 × 10−11), PDLIM5 in EAs (P = 2.01 × 10−8), and METAP in AAs (P = 3.35 × 10−8). We also identified a novel GWS association (1.17 × 10−10) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. PMID:24166409

  9. Genomic analyses of tropical beef cattle fertility based on genotyping pools of Brahman cows with unknown pedigree.

    Science.gov (United States)

    Reverter, A; Porto-Neto, L R; Fortes, M R S; McCulloch, R; Lyons, R E; Moore, S; Nicol, D; Henshall, J; Lehnert, S A

    2016-10-01

    We introduce an innovative approach to lowering the overall cost of obtaining genomic EBV (GEBV) and encourage their use in commercial extensive herds of Brahman beef cattle. In our approach, the DNA genotyping of cow herds from 2 independent properties was performed using a high-density bovine SNP chip on DNA from pooled blood samples, grouped according to the result of a pregnancy test following their first and second joining opportunities. For the DNA pooling strategy, 15 to 28 blood samples from the same phenotype and contemporary group were allocated to pools. Across the 2 properties, a total of 183 pools were created representing 4,164 cows. In addition, blood samples from 309 bulls from the same properties were also taken. After genotyping and quality control, 74,584 remaining SNP were used for analyses. Pools and individual DNA samples were related by means of a "hybrid" genomic relationship matrix. The pooled genotyping analysis of 2 large and independent commercial populations of tropical beef cattle was able to recover significant and plausible associations between SNP and pregnancy test outcome. We discuss 24 SNP with significant association ( Brahman herds managed under extensive pastoral conditions.

  10. Genomic analyses of metal resistance genes in three plant growth promoting bacteria of legume plants in Northwest mine tailings, China.

    Science.gov (United States)

    Xie, Pin; Hao, Xiuli; Herzberg, Martin; Luo, Yantao; Nies, Dietrich H; Wei, Gehong

    2015-01-01

    To better understand the diversity of metal resistance genetic determinant from microbes that survived at metal tailings in northwest of China, a highly elevated level of heavy metal containing region, genomic analyses was conducted using genome sequence of three native metal-resistant plant growth promoting bacteria (PGPB). It shows that: Mesorhizobium amorphae CCNWGS0123 contains metal transporters from P-type ATPase, CDF (Cation Diffusion Facilitator), HupE/UreJ and CHR (chromate ion transporter) family involved in copper, zinc, nickel as well as chromate resistance and homeostasis. Meanwhile, the putative CopA/CueO system is expected to mediate copper resistance in Sinorhizobium meliloti CCNWSX0020 while ZntA transporter, assisted with putative CzcD, determines zinc tolerance in Agrobacterium tumefaciens CCNWGS0286. The greenhouse experiment provides the consistent evidence of the plant growth promoting effects of these microbes on their hosts by nitrogen fixation and/or indoleacetic acid (IAA) secretion, indicating a potential in-site phytoremediation usage in the mining tailing regions of China. Copyright © 2014. Published by Elsevier B.V.

  11. Genomic analyses of metal resistance genes in three plant growth promoting bacteria of legume plants in Northwest mine tailings, China

    Institute of Scientific and Technical Information of China (English)

    Pin Xie; Xiuli Hao; Martin Herzberg; Yantao Luo; Dietrich H.Nies; Gehong Wei

    2015-01-01

    To better understand the diversity of metal resistance genetic determinant from microbes that survived at metal tailings in northwest of China,a highly elevated level of heavy metal containing region,genomic analyses was conducted using genome sequence of three native metal-resistant plant growth promoting bacteria (PGPB).It shows that:Mesorhizobium amorphae CCNWGS0123 contains metal ~nsporters from P-type ATPase,CDF (Cation Diffusion Facilitator),HupE/UreJ and CHR (chromate ion transporter) family involved in copper,zinc,nickel as well as chromate resistance and homeostasis.Meanwhile,the putative CopA/CueO system is expected to mediate copper resistance in Sinorhizobium meliloti CCNWSX0020 while ZntA transporter,assisted with putative CzcD,determines zinc tolerance in Agrobacterium tumefaciens CCNWGS0286.The greenhouse experiment provides the consistent evidence of the plant growth promoting effects of these microbes on their hosts by nitrogen fixation and/or indoleacetic acid (IAA) secretion,indicating a potential in-site phytoremediation usage in the mining tailing regions of China.

  12. Comparative genomic and functional analyses: unearthing the diversity and specificity of nematicidal factors in Pseudomonas putida strain 1A00316

    Science.gov (United States)

    Guo, Jing; Jing, Xueping; Peng, Wen-Lei; Nie, Qiyu; Zhai, Yile; Shao, Zongze; Zheng, Longyu; Cai, Minmin; Li, Guangyu; Zuo, Huaiyu; Zhang, Zhitao; Wang, Rui-Ru; Huang, Dian; Cheng, Wanli; Yu, Ziniu; Chen, Ling-Ling; Zhang, Jibin

    2016-01-01

    We isolated Pseudomonas putida (P. putida) strain 1A00316 from Antarctica. This bacterium has a high efficiency against Meloidogyne incognita (M. incognita) in vitro and under greenhouse conditions. The complete genome of P. putida 1A00316 was sequenced using PacBio single molecule real-time (SMRT) technology. A comparative genomic analysis of 16 Pseudomonas strains revealed that although P. putida 1A00316 belonged to P. putida, it was phenotypically more similar to nematicidal Pseudomonas fluorescens (P. fluorescens) strains. We characterized the diversity and specificity of nematicidal factors in P. putida 1A00316 with comparative genomics and functional analysis, and found that P. putida 1A00316 has diverse nematicidal factors including protein alkaline metalloproteinase AprA and two secondary metabolites, hydrogen cyanide and cyclo-(l-isoleucyl-l-proline). We show for the first time that cyclo-(l-isoleucyl-l-proline) exhibit nematicidal activity in P. putida. Interestingly, our study had not detected common nematicidal factors such as 2,4-diacetylphloroglucinol (2,4-DAPG) and pyrrolnitrin in P. putida 1A00316. The results of the present study reveal the diversity and specificity of nematicidal factors in P. putida strain 1A00316. PMID:27384076

  13. Transcriptional analyses of the region of the equine herpesvirus type 4 genome encoding glycoproteins I and E.

    Science.gov (United States)

    Damiani, A M; Jang, H K; Matsumura, T; Yokoyama, N; Miyazawa, T; Mikami, T

    1999-01-01

    To map the transcripts encoding the equine herpesvirus type 4 (EHV-4) glycoproteins I (gI) and E (gE), transcriptional analyses were performed at the right part of the unique short segment of EHV-4 genome. The results revealed that the gI gene is encoded by a 1.6-kb transcript which is 3' coterminal with a 3.0-kb gD mRNA while the gE gene is encoded by two transcripts of 3.5- and 2.4-kb in size. The transcriptional patterns described in this study for the EHV-4 gI and gE are similar to those found in the equivalent region of herpes simplex virus type 1 and feline herpesvirus type 1. Characterization of EHV-4 gI and gE glycoprotein genes may facilitate future studies to define their roles in the EHV-4 infection.

  14. Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer.

    Science.gov (United States)

    Zhang, Jialing; Yan, Bin; Späth, Stephan Stanislaw; Qun, Hu; Cornelius, Shaleeka; Guan, Daogang; Shao, Jiaofang; Hagiwara, Koichi; Van Waes, Carter; Chen, Zhong; Su, Xiulan; Bi, Yongyi

    2015-01-01

    Colorectal cancer (CRC) is a heterogeneous disease that is associated with a gradual accumulation of genetic and epigenetic alterations. Among all CRC stages, stage II tumors are highly heterogeneous with a high relapse rate in about 20-25 % of stage II CRC patients following surgery. Thus, a comprehensive analysis of gene signatures to identify aggressive and metastatic phenotypes in stage II CRC is desired for a more accurate disease classification and outcome prediction. By utilizing a Cancer Array, containing 440 oncogenes and tumor suppressors to profile mRNA expression, we identified a larger number of differentially expressed genes in poorly differentiated stage II colorectal adenocarcinoma tissues, compared to their matched normal tissues. Ontology and Ingenuity Pathway Analysis (IPA) indicated that these genes are involved in functional mechanisms associated with several transcription factors. Genomic alterations of these genes were also investigated through The Cancer Genome Atlas (TCGA) database, utilizing 195 published CRC specimens. The percentage of genomic alterations in these genes was ranked based on their mRNA expression, copy number variations and mutations. This data was further combined with published microarray studies from a large set of CRC tumors classified based on prognostic features. This led to the identification of eight candidate genes including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15 that were associated with the progressive phenotype. In particular, RPN2 and HMGB1 displayed a higher genomic alteration frequency in CRC, compared to eight other major solid cancers. Immunohistochemistry was performed on additional 78 stage I-IV CRC samples, where RPN2 protein immunostaining exhibited a significant association with stage III/IV tumors, distant metastasis, and poor differentiation, indicating that RPN2 expression is associated with poor prognosis. Further, our study revealed significant transcriptional regulatory

  15. Morphological and comparative genomic analyses of pathogenic and non-pathogenic Fusarium solani isolated from Dalbergia sissoo.

    Science.gov (United States)

    Arif, M; Zaidi, N W; Haq, Q M R; Singh, Y P; Taj, G; Kar, C S; Singh, U S

    2015-06-01

    Sissoo or shisham (Dalbergia sissoo Roxb.) is one of the finest wood of South Asia. Fusarium solani is a causal organism of sissoo wilt, decline, or dieback. It is also a potential causal organism associated with other valuable tree species. Thirty-eight Fusarium isolates including 24 F. solani and 14 Fusarium sp., were obtained in 2005 from different geographical locations in India. All 38 (18 pathogenic and 20 non-pathogenic) isolates were characterized for genomic analysis, growth behaviour, pigmentation and sensitivity to carbendazim. Based on growth pattern, growth rate, pigmentation and sensitivity to carbendazim, all 38 isolates showed a wide range of variability, but no correlation with pathogenicity or geographical distribution. Three techniques were used for comparative genomic analysis: random amplified polymorphic DNA (RAPD); inter simple sequence repeats (ISSR); and simple sequence repeats (SSR). A total of 90 primers targeting different genome regions resulted a total of 1159 loci with an average of 12.88 loci per primer. These primers showed high genomic variability among the isolates. The maximum loci (14.64) per primer were obtained with RAPD. The total variation of the first five principal components for RAPD, ISSR, SSR and combined analysis were estimated as 47.42, 48.21, 46.30 and 46.78 %, respectively. Among the molecular markers, highest Pearson correlation value (r = 0.957) was recorded with combination of RAPD and SSR followed by RAPD and ISSR (r = 0.952), and SSR and ISSR (r = 0.942). The combination of these markers would be similarly effective as single marker system i.e. RAPD, ISSR and SSR. Based on polymorphic information content (PIC = 0.619) and highest coefficient (r = 0.995), RAPD was found to be the most efficient marker system compared to ISSR and SSR. This study will assist in understanding the population biology of wilt causing phytopathogen, F. solani, and in assisting with integrated disease management measures.

  16. Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Zhao, Z; Xu, J; Chen, J; Kim, S; Reimers, M; Bacanu, S-A; Yu, H; Liu, C; Sun, J; Wang, Q; Jia, P; Xu, F; Zhang, Y; Kendler, K S; Peng, Z; Chen, X

    2015-05-01

    Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q⩽0.01, 53 genes; q⩽0.05, 213 genes; q⩽0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (Pgenes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. Functional analyses of these genes revealed an interconnected pathway network centered on lysosomal function and the regulation of actin cytoskeleton. These pathways and their interacting network were principally confirmed by an independent transcriptome sequencing data set of the hippocampus. Dysregulation of lysosomal function and cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis, exocytosis, vesicle trafficking, neuronal maturation and migration, neurite outgrowth and synaptic density and plasticity, and different aspects of these processes have been implicated in SCZ and BPD.

  17. Spliced leader-based metatranscriptomic analyses lead to recognition of hidden genomic features in dinoflagellates.

    Science.gov (United States)

    Lin, Senjie; Zhang, Huan; Zhuang, Yunyun; Tran, Bao; Gill, John

    2010-11-16

    Environmental transcriptomics (metatranscriptomics) for a specific lineage of eukaryotic microbes (e.g., Dinoflagellata) would be instrumental for unraveling the genetic mechanisms by which these microbes respond to the natural environment, but it has not been exploited because of technical difficulties. Using the recently discovered dinoflagellate mRNA-specific spliced leader as a selective primer, we constructed cDNA libraries (e-cDNAs) from one marine and two freshwater plankton assemblages. Small-scale sequencing of the e-cDNAs revealed functionally diverse transcriptomes proven to be of dinoflagellate origin. A set of dinoflagellate common genes and transcripts of dominant dinoflagellate species were identified. Further analyses of the dataset prompted us to delve into the existing, largely unannotated dinoflagellate EST datasets (DinoEST). Consequently, all four nucleosome core histones, two histone modification proteins, and a nucleosome assembly protein were detected, clearly indicating the presence of nucleosome-like machinery long thought not to exist in dinoflagellates. The isolation of rhodopsin from taxonomically and ecotypically diverse dinoflagellates and its structural similarity and phylogenetic affinity to xanthorhodopsin suggest a common genetic potential in dinoflagellates to use solar energy nonphotosynthetically. Furthermore, we found 55 cytoplasmic ribosomal proteins (RPs) from the e-cDNAs and 24 more from DinoEST, showing that the dinoflagellate phylum possesses all 79 eukaryotic RPs. Our results suggest that a sophisticated eukaryotic molecular machine operates in dinoflagellates that likely encodes many more unsuspected physiological capabilities and, meanwhile, demonstrate that unique spliced leaders are useful for profiling lineage-specific microbial transcriptomes in situ.

  18. The Mitochondrial Genomes of Aquila fasciata and Buteo lagopus (Aves, Accipitriformes): Sequence, Structure and Phylogenetic Analyses

    OpenAIRE

    2015-01-01

    The family Accipitridae is one of the largest groups of non-passerine birds, including 68 genera and 243 species globally distributed. In the present study, we determined the complete mitochondrial sequences of two species of accipitrid, namely Aquila fasciata and Buteo lagopus, and conducted a comparative mitogenome analysis across the family. The mitogenome length of A. fasciata and B. lagopus are 18,513 and 18,559 bp with an A + T content of 54.2% and 55.0%, respectively. For both the two ...

  19. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    OpenAIRE

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LA...

  20. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

    OpenAIRE

    Barrett, Jeffrey C.; Lee, James C.; Lees, Charles W.; Prescott, Natalie J.; Anderson, Carl A.; Phillips, Anne; Wesley, Emma; Parnell, Kirstie; Zhang, Hu; DRUMMOND, HAZEL; Elaine R Nimmo; Massey, Dunecan; Blaszczyk, Kasia; Elliott, Timothy; Cotterill, Lynn

    2009-01-01

    Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P < 1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least o...

  1. Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc.

    Science.gov (United States)

    Paulson, Kelly G; Lemos, Bianca D; Feng, Bin; Jaimes, Natalia; Peñas, Pablo F; Bi, Xiaohui; Maher, Elizabeth; Cohen, Lisa; Leonard, J Helen; Granter, Scott R; Chin, Lynda; Nghiem, Paul

    2009-06-01

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

  2. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  3. Genome-wide diet-gene interaction analyses for risk of colorectal cancer.

    Science.gov (United States)

    Figueiredo, Jane C; Hsu, Li; Hutter, Carolyn M; Lin, Yi; Campbell, Peter T; Baron, John A; Berndt, Sonja I; Jiao, Shuo; Casey, Graham; Fortini, Barbara; Chan, Andrew T; Cotterchio, Michelle; Lemire, Mathieu; Gallinger, Steven; Harrison, Tabitha A; Le Marchand, Loic; Newcomb, Polly A; Slattery, Martha L; Caan, Bette J; Carlson, Christopher S; Zanke, Brent W; Rosse, Stephanie A; Brenner, Hermann; Giovannucci, Edward L; Wu, Kana; Chang-Claude, Jenny; Chanock, Stephen J; Curtis, Keith R; Duggan, David; Gong, Jian; Haile, Robert W; Hayes, Richard B; Hoffmeister, Michael; Hopper, John L; Jenkins, Mark A; Kolonel, Laurence N; Qu, Conghui; Rudolph, Anja; Schoen, Robert E; Schumacher, Fredrick R; Seminara, Daniela; Stelling, Deanna L; Thibodeau, Stephen N; Thornquist, Mark; Warnick, Greg S; Henderson, Brian E; Ulrich, Cornelia M; Gauderman, W James; Potter, John D; White, Emily; Peters, Ulrike

    2014-04-01

    Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.

  4. Genomic analyses of musashi1 downstream targets show a strong association with cancer-related processes.

    Science.gov (United States)

    de Sousa Abreu, Raquel; Sanchez-Diaz, Patricia C; Vogel, Christine; Burns, Suzanne C; Ko, Daijin; Burton, Tarea L; Vo, Dat T; Chennasamudaram, Soudhamini; Le, Shu-Yun; Shapiro, Bruce A; Penalva, Luiz O F

    2009-05-01

    Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal functions in stem cell maintenance, nervous system development, and tumorigenesis. Despite its importance, only three direct mRNA targets have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has been shown to affect their translation by binding to short elements located in the 3'-untranslated region. To better understand Msi1 functions, we initially performed an RIP-Chip analysis in HEK293T cells; this method consists of isolation of specific RNA-protein complexes followed by identification of the RNA component via microarrays. A group of 64 mRNAs was found to be enriched in the Msi1-associated population compared with controls. These genes belong to two main functional categories pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell differentiation, and apoptosis and 2) protein modification (including ubiquitination and ubiquitin cycle). To corroborate our findings, we examined the impact of Msi1 expression on both mRNA (transcriptomic) and protein (proteomic) expression levels. Genes whose mRNA levels were affected by Msi1 expression have a Gene Ontology distribution similar to RIP-Chip results, reinforcing Msi1 participation in cancer-related processes. The proteomics study revealed that Msi1 can have either positive or negative effects on gene expression of its direct targets. In summary, our results indicate that Msi1 affects a network of genes and could function as a master regulator during development and tumor formation.

  5. Genome-wide diet-gene interaction analyses for risk of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jane C Figueiredo

    2014-04-01

    Full Text Available Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3 and processed meat consumption (OR = 1.17; p = 8.7E-09, which was consistently observed across studies (p heterogeneity = 0.78. The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively and null among those with the GG genotype (OR = 1.03. Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.

  6. Genome-Wide Analyses of the Soybean F-Box Gene Family in Response to Salt Stress.

    Science.gov (United States)

    Jia, Qi; Xiao, Zhi-Xia; Wong, Fuk-Ling; Sun, Song; Liang, Kang-Jing; Lam, Hon-Ming

    2017-04-12

    The F-box family is one of the largest gene families in plants that regulate diverse life processes, including salt responses. However, the knowledge of the soybean F-box genes and their roles in salt tolerance remains limited. Here, we conducted a genome-wide survey of the soybean F-box family, and their expression analysis in response to salinity via in silico analysis of online RNA-sequencing (RNA-seq) data and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to predict their potential functions. A total of 725 potential F-box proteins encoded by 509 genes were identified and classified into 9 subfamilies. The gene structures, conserved domains and chromosomal distributions were characterized. There are 76 pairs of duplicate genes identified, including genome-wide segmental and tandem duplication events, which lead to the expansion of the number of F-box genes. The in silico expression analysis showed that these genes would be involved in diverse developmental functions and play an important role in salt response. Our qRT-PCR analysis confirmed 12 salt-responding F-box genes. Overall, our results provide useful information on soybean F-box genes, especially their potential roles in salt tolerance.

  7. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

    Science.gov (United States)

    Tang, Wenbo; Kowgier, Matthew; Loth, Daan W.; Soler Artigas, María; Joubert, Bonnie R.; Hodge, Emily; Gharib, Sina A.; Smith, Albert V.; Ruczinski, Ingo; Gudnason, Vilmundur; Mathias, Rasika A.; Harris, Tamara B.; Hansel, Nadia N.; Launer, Lenore J.; Barnes, Kathleen C.; Hansen, Joyanna G.; Albrecht, Eva; Aldrich, Melinda C.; Allerhand, Michael; Barr, R. Graham; Brusselle, Guy G.; Couper, David J.; Curjuric, Ivan; Davies, Gail; Deary, Ian J.; Dupuis, Josée; Fall, Tove; Foy, Millennia; Franceschini, Nora; Gao, Wei; Gläser, Sven; Gu, Xiangjun; Hancock, Dana B.; Heinrich, Joachim; Hofman, Albert; Imboden, Medea; Ingelsson, Erik; James, Alan; Karrasch, Stefan; Koch, Beate; Kritchevsky, Stephen B.; Kumar, Ashish; Lahousse, Lies; Li, Guo; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Lohman, Kurt; Lumley, Thomas; McArdle, Wendy L.; Meibohm, Bernd; Morris, Andrew P.; Morrison, Alanna C.; Musk, Bill; North, Kari E.; Palmer, Lyle J.; Probst-Hensch, Nicole M.; Psaty, Bruce M.; Rivadeneira, Fernando; Rotter, Jerome I.; Schulz, Holger; Smith, Lewis J.; Sood, Akshay; Starr, John M.; Strachan, David P.; Teumer, Alexander; Uitterlinden, André G.; Völzke, Henry; Voorman, Arend; Wain, Louise V.; Wells, Martin T.; Wilk, Jemma B.; Williams, O. Dale; Heckbert, Susan R.; Stricker, Bruno H.; London, Stephanie J.; Fornage, Myriam; Tobin, Martin D.; O′Connor, George T.; Hall, Ian P.; Cassano, Patricia A.

    2014-01-01

    Background Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. PMID:24983941

  8. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

    Directory of Open Access Journals (Sweden)

    Wenbo Tang

    Full Text Available Genome-wide association studies (GWAS have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1 in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7. In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8 at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  9. Bioinformatics analyses of the differences between lung adenocarcinoma and squamous cell carcinoma using The Cancer Genome Atlas expression data.

    Science.gov (United States)

    Sun, Fenghao; Yang, Xiaodong; Jin, Yulin; Chen, Li; Wang, Lin; Shi, Mengkun; Zhan, Cheng; Shi, Yu; Wang, Qun

    2017-07-01

    The present study aimed to explore gene and microRNA (miRNA) expression differences between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified by analyzing mRNA and miRNA expression data in normal and cancerous lung tissues that were obtained from The Cancer Genome Atlas database. A total of 778 DEGs and 7 DEMs were identified. Altered gene functions and signaling pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which revealed that DEGs were significantly enriched in extracellular matrix organization, cell differentiation, negative regulation of toll signaling pathway, and several other terms and pathways. Transcription factor (TF)‑miRNA‑gene networks in LUAD and LUSC were predicted using the TargetScan, Miranda, and TRANSFAC databases, which revealed the regulatory links among the TFs, DEMs, and DEGs. The central TFs, i.e., the TFs in the middle of the TF‑miRNA‑gene network, of LUAD and LUSC were similar. Although LUAD and LUSC shared similar miRNAs in the predicted networks, miR‑29b‑3p was demonstrated to be upregulated only in LUAD, whereas miR‑1, miR‑105‑5p, and miR‑193b‑5p were altered in LUSC. These findings may improve our understanding of the different molecular mechanisms in non‑small cell lung cancers and may promote new and accurate strategies for prevention, diagnosis, and treatment.

  10. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    Science.gov (United States)

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  11. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    Science.gov (United States)

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

  12. Genomic and Functional Analyses of Rhodococcus equi Phages ReqiPepy6, ReqiPoco6, ReqiPine5, and ReqiDocB7 ▿

    Science.gov (United States)

    Summer, E. J.; Liu, M.; Gill, J. J.; Grant, M.; Chan-Cortes, T. N.; Ferguson, L.; Janes, C.; Lange, K.; Bertoli, M.; Moore, C.; Orchard, R. C.; Cohen, N. D.; Young, R.

    2011-01-01

    The isolation and results of genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiDocB7, ReqiPine5, and ReqiPoco6 (hereafter referred to as Pepy6, DocB7, Pine5, and Poco6, respectively) are reported. Two phages, Pepy6 and Poco6, more than 75% identical, exhibited genome organization and protein sequence likeness to Lactococcus lactis phage 1706 and clostridial prophage elements. An unusually high fraction, 27%, of Pepy6 and Poco6 proteins were predicted to possess at least one transmembrane domain, a value much higher than the average of 8.5% transmembrane domain-containing proteins determined from a data set of 36,324 phage protein entries. Genome organization and protein sequence comparisons place phage Pine5 as the first nonmycobacteriophage member of the large Rosebush cluster. DocB7, which had the broadest host range among the four isolates, was not closely related to any phage or prophage in the database, and only 23 of 105 predicted encoded proteins could be assigned a functional annotation. Because of the relationship of Rhodococcus to Mycobacterium, it was anticipated that these phages should exhibit some of the features characteristic of mycobacteriophages. Traits that were identified as shared by the Rhodococcus phages and mycobacteriophages include the prevalent long-tailed morphology and the presence of genes encoding LysB-like mycolate-hydrolyzing lysis proteins. Application of DocB7 lysates to soils amended with a host strain of R. equi reduced recoverable bacterial CFU, suggesting that phage may be useful in limiting R. equi load in the environment while foals are susceptible to infection. PMID:21097585

  13. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia.

    Science.gov (United States)

    Briese, Thomas; Mishra, Nischay; Jain, Komal; Zalmout, Iyad S; Jabado, Omar J; Karesh, William B; Daszak, Peter; Mohammed, Osama B; Alagaili, Abdulaziz N; Lipkin, W Ian

    2014-04-29

    ABSTRACT Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection. IMPORTANCE In most cases of Middle East respiratory syndrome (MERS), the route for human infection with the causative agent, MERS coronavirus (MERS-CoV), is unknown. Antibodies to and viral nucleic acids of MERS-CoV have been found in dromedaries, suggesting the possibility that they may serve as a reservoir or vector for human infection. However, neither whole viral genomic sequence nor infectious virus has been isolated from dromedaries or other animals in Saudi Arabia. Here, we report recovery of MERS-CoV from nasal swabs of dromedaries, demonstrate that MERS-CoV whole-genome consensus sequences from dromedaries and humans are indistinguishable, and show that dromedaries can be simultaneously infected with more than one MERS-CoV. Together with data indicating widespread dromedary infection in the Kingdom of Saudi Arabia, these findings support the plausibility of a role for dromedaries in human infection.

  14. Meta-analyses of genome-wide association studies identify multiple novel loci associated with pulmonary function

    Science.gov (United States)

    Hancock, Dana B.; Eijgelsheim, Mark; Wilk, Jemma B.; Gharib, Sina A.; Loehr, Laura R.; Marciante, Kristin D.; Franceschini, Nora; van Durme, Yannick M.T.A.; Chen, Ting-hsu; Barr, R. Graham; Schabath, Matthew B.; Couper, David J.; Brusselle, Guy G.; Psaty, Bruce M.; van Duijn, Cornelia M.; Rotter, Jerome I.; Uitterlinden, André G.; Hofman, Albert; Punjabi, Naresh M.; Rivadeneira, Fernando; Morrison, Alanna C.; Enright, Paul L.; North, Kari E.; Heckbert, Susan R.; Lumley, Thomas; Stricker, Bruno H.Ch.; O’Connor, George T.; London, Stephanie J.

    2010-01-01

    Measurements of lung function by spirometry are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important measures, forced expiratory volume in the first second (FEV1) and its ratio to forced vital capacity (FEV1/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE consortium studies: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Rotterdam Study (RS). We identified eight loci associated with FEV1/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1, and HTR4) and one locus associated with FEV1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (PPID1) replicated with the SpiroMeta consortium. Our findings of novel loci influencing pulmonary function may offer insights into chronic lung disease pathogenesis. PMID:20010835

  15. An atypical human induced pluripotent stem cell line with a complex, stable, and balanced genomic rearrangement including a large de novo 1q uniparental disomy.

    Science.gov (United States)

    Steichen, Clara; Maluenda, Jérôme; Tosca, Lucie; Luce, Eléanor; Pineau, Dominique; Dianat, Noushin; Hannoun, Zara; Tachdjian, Gérard; Melki, Judith; Dubart-Kupperschmitt, Anne

    2015-03-01

    Human induced pluripotent stem cells (hiPSCs) hold great promise for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts.

  16. Pronounced genetic differentiation and recent secondary contact in the mangrove tree Lumnitzera racemosa revealed by population genomic analyses

    Science.gov (United States)

    Li, Jianfang; Yang, Yuchen; Chen, Qipian; Fang, Lu; He, Ziwen; Guo, Wuxia; Qiao, Sitan; Wang, Zhengzhen; Guo, Miaomiao; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2016-01-01

    Systematically investigating the impacts of Pleistocene sea-level fluctuations on mangrove plants may provide a better understanding of their demographic history and useful information for their conservation. Therefore, we conducted population genomic analyses of 88 nuclear genes to explore the population dynamics of a mangrove tree Lumnitzera racemosa across the Indo-West Pacific region. Our results revealed pronounced genetic differentiation in this species between the populations from the Indian Ocean and the Pacific Ocean, which may be attributable to the long-term isolation between the western and eastern coasts of the Malay Peninsula during sea-level drops in the Pleistocene glacial periods. The mixing of haplotypes from the two highly divergent groups was identified in a Cambodian population at almost all 88 nuclear genes, suggesting genetic admixture of the two lineages at the boundary region. Similar genetic admixture was also found in other populations from Southeast Asia based on the Bayesian clustering analysis of six nuclear genes, which suggests extensive and recent secondary contact of the two divergent lineages in Southeast Asia. Computer simulations indicated substantial migration from the Indian Ocean towards the South China Sea, which likely results in the genetic admixture in Southeast Asia. PMID:27380895

  17. Genome-Wide Association and Transcriptome Analyses Reveal Candidate Genes Underlying Yield-determining Traits in Brassica napus

    Science.gov (United States)

    Lu, Kun; Peng, Liu; Zhang, Chao; Lu, Junhua; Yang, Bo; Xiao, Zhongchun; Liang, Ying; Xu, Xingfu; Qu, Cunmin; Zhang, Kai; Liu, Liezhao; Zhu, Qinlong; Fu, Minglian; Yuan, Xiaoyan; Li, Jiana

    2017-01-01

    Yield is one of the most important yet complex crop traits. To improve our understanding of the genetic basis of yield establishment, and to identify candidate genes responsible for yield improvement in Brassica napus, we performed genome-wide association studies (GWAS) for seven yield-determining traits [main inflorescence pod number (MIPN), branch pod number (BPN), pod number per plant (PNP), seed number per pod (SPP), thousand seed weight, main inflorescence yield (MIY), and branch yield], using data from 520 diverse B. napus accessions from two different yield environments. In total, we detected 128 significant single nucleotide polymorphisms (SNPs), 93 of which were revealed as novel by integrative analysis. A combination of GWAS and transcriptome sequencing on 21 haplotype blocks from samples pooled by four extremely high-yielding or low-yielding accessions revealed the differential expression of 14 crucial candiate genes (such as Bna.MYB83, Bna.SPL5, and Bna.ROP3) associated with multiple traits or containing multiple SNPs associated with the same trait. Functional annotation and expression pattern analyses further demonstrated that these 14 candiate genes might be important in developmental processes and biomass accumulation, thus affecting the yield establishment of B. napus. These results provide valuable information for understanding the genetic mechanisms underlying the establishment of high yield in B. napus, and lay the foundation for developing high-yielding B. napus varieties. PMID:28261256

  18. Genomic and Phenotypic Analyses Reveal the Emergence of an Atypical Salmonella enterica Serovar Senftenberg Variant in China

    KAUST Repository

    Abd El Ghany, Moataz

    2016-05-25

    Human infections with Salmonella enterica subspecies enterica serovar Senftenberg are often associated with exposure to poultry flocks, farm environments, or contaminated food. The recent emergence of multidrug-resistant isolates has raised public health concerns. In this study, comparative genomics and phenotypic analysis were used to characterize 14 Salmonella Senftenberg clinical isolates recovered from multiple outbreaks in Shenzhen and Shanghai, China, between 2002 and 2011. Single-nucleotide polymorphism analyses identified two phylogenetically distinct clades of S. Senftenberg, designated SC1 and SC2, harboring variations in Salmonella pathogenicity island 1 (SPI-1) and SPI-2 and exhibiting distinct biochemical and phenotypic signatures. Although the two variants shared the same serotype, the SC2 isolates of sequence type 14 (ST14) harbored intact SPI-1 and -2 and hence were characterized by possessing efficient invasion capabilities. In contrast, the SC1 isolates had structural deletion patterns in both SPI-1 and -2 that correlated with an impaired capacity to invade cultured human cells and also the year of their isolation. These atypical SC1 isolates also lacked the capacity to produce hydrogen sulfide. These findings highlight the emergence of atypical Salmonella Senftenberg variants in China and provide genetic validation that variants lacking SPI-1 and regions of SPI-2, which leads to impaired invasion capacity, can still cause clinical disease. These data have identified an emerging public health concern and highlight the need to strengthen surveillance to detect the prevalence and transmission of nontyphoidal Salmonella species.

  19. Genome-wide analyses reveal lineage specific contributions of positive selection and recombination to the evolution of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Sun Qi

    2008-08-01

    Full Text Available Abstract Background The genus Listeria includes two closely related pathogenic and non-pathogenic species, L. monocytogenes and L. innocua. L. monocytogenes is an opportunistic human foodborne and animal pathogen that includes two common lineages. While lineage I is more commonly found among human listeriosis cases, lineage II appears to be overrepresented among isolates from foods and environmental sources. This study used the genome sequences for one L. innocua strain and four L. monocytogenes strains representing lineages I and II, to characterize the contributions of positive selection and recombination to the evolution of the L. innocua/L. monocytogenes core genome. Results Among the 2267 genes in the L. monocytogenes/L. innocua core genome, 1097 genes showed evidence for recombination and 36 genes showed evidence for positive selection. Positive selection was strongly associated with recombination. Specifically, 29 of the 36 genes under positive selection also showed evidence for recombination. Recombination was more common among isolates in lineage II than lineage I; this trend was confirmed by sequencing five genes in a larger isolate set. Positive selection was more abundant in the ancestral branch of lineage II (20 genes as compared to the ancestral branch of lineage I (9 genes. Additional genes under positive selection were identified in the branch separating the two species; for this branch, genes in the role category "Cell wall and membrane biogenesis" were significantly more likely to have evidence for positive selection. Positive selection of three genes was confirmed in a larger isolate set, which also revealed occurrence of multiple premature stop codons in one positively selected gene involved in flagellar motility (flaR. Conclusion While recombination and positive selection both contribute to evolution of L. monocytogenes, the relative contributions of these evolutionary forces seem to differ by L. monocytogenes lineages and

  20. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    Directory of Open Access Journals (Sweden)

    Matthews Jason

    2011-07-01

    Full Text Available Abstract Background The aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor (TF that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS. AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR, extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'. Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t > 0.999. Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation.

  1. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    Science.gov (United States)

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296

  2. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

    Science.gov (United States)

    Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E; Hosseini, S Mohsen; Paterson, Andrew D; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W; Williams, Cathy; Oostra, Ben A; Teo, Yik-Ying; Hammond, Christopher J; Stambolian, Dwight; Mackey, David A; Klaver, Caroline C W; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N

    2013-08-08

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Nucleotide sequence analyses of genomic RNAs of peanut stunt virus Mi, the type strain representative of a novel PSV subgroup from China

    NARCIS (Netherlands)

    Yan, L.; Xu, Z.; Goldbach, R.W.; Chen, Y.K.; Prins, M.W.

    2005-01-01

    The complete nucleotide sequence of Peanut stunt virus strain Mi (PSV-Mi) from China was determined and compared to other viruses of the genus Cucumovirus. The tripartite genome of PSV-Mi encoded five open reading frames (ORFs) typical of cucumoviruses. Distance analyses of four ORFs indicated that

  4. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    NARCIS (Netherlands)

    Kar, S.P.; Beesley, J.; Olama, A. Amin Al; Michailidou, K.; Tyrer, J.; Kote-Jarai, Z.; Lawrenson, K.; Lindstrom, S.; Ramus, S.J.; Thompson, D.J.; Kibel, A.S.; Dansonka-Mieszkowska, A.; Michael, A.; Dieffenbach, A.K.; Gentry-Maharaj, A.; Whittemore, A.S.; Wolk, A.; Monteiro, A.; Peixoto, A.; Kierzek, A.; Cox, A; Rudolph, A.; Gonzalez-Neira, A.; Wu, A.H.; Lindblom, A.; Swerdlow, A.; Ziogas, A.; Ekici, A.B.; Burwinkel, B.; Karlan, B.Y.; Nordestgaard, B.G.; Blomqvist, C.; Phelan, C.; McLean, C.; Pearce, C.L.; Vachon, C.; Cybulski, C.; Slavov, C.; Stegmaier, C.; Maier, C.; Ambrosone, C.B.; Hogdall, C.K.; Teerlink, C.C.; Kang, D.; Tessier, D.C.; Schaid, D.J.; Stram, D.O.; Cramer, D.W; Neal, D.E.; Eccles, D.; Flesch-Janys, D.; Edwards, D.R.; Wokozorczyk, D.; Levine, D.A.; Yannoukakos, D.; Sawyer, E.J.; Bandera, E.V.; Poole, E.M.; Goode, E.L.; Khusnutdinova, E.; Hogdall, E.; Song, F.; Bruinsma, F.; Heitz, F.; Modugno, F.; Hamdy, F.C.; Wiklund, F.; Giles, G.G.; Olsson, H.; Wildiers, H.; Ulmer, H.U.; Pandha, H.; Risch, H.A.; Darabi, H.; Salvesen, H.B.; Nevanlinna, H.; Gronberg, H.; Brenner, H.; Brauch, H.; Anton-Culver, H.; Song, H.; Lim, H.Y.; McNeish, I.; Campbell, I.; Vergote, I.; Gronwald, J.; Lubinski, J.; Stanford, J.L.; Benitez, J.; Doherty, J.A.; Permuth, J.B.; Chang-Claude, J.; Donovan, J.L.; Dennis, J.; Schildkraut, J.M.; Schleutker, J.; Hopper, J.L.; Kupryjanczyk, J.; Park, J.Y.; Figueroa, J.; Kiemeney, L.A.; Massuger, L.F.A.G.

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and

  5. A comparative study of nemertean complete mitochondrial genomes, including two new ones for Nectonemertes cf. mirabilis and Zygeupolia rubens, may elucidate the fundamental pattern for the phylum Nemertea

    Directory of Open Access Journals (Sweden)

    Chen Hai-Xia

    2012-04-01

    Full Text Available Abstract Background The mitochondrial genome is important for studying genome evolution as well as reconstructing the phylogeny of organisms. Complete mitochondrial genome sequences have been reported for more than 2200 metazoans, mainly vertebrates and arthropods. To date, from a total of about 1275 described nemertean species, only three complete and two partial mitochondrial DNA sequences from nemerteans have been published. Here, we report the entire mitochondrial genomes for two more nemertean species: Nectonemertes cf. mirabilis and Zygeupolia rubens. Results The sizes of the entire mitochondrial genomes are 15365 bp for N. cf. mirabilis and 15513 bp for Z. rubens. Each circular genome contains 37 genes and an AT-rich non-coding region, and overall nucleotide composition is AT-rich. In both species, there is significant strand asymmetry in the distribution of nucleotides, with the coding strand being richer in T than A and in G than C. The AT-rich non-coding regions of the two genomes have some repeat sequences and stem-loop structures, both of which may be associated with the initiation of replication or transcription. The 22 tRNAs show variable substitution patterns in nemerteans, with higher sequence conservation in genes located on the H strand. Gene arrangement of N. cf. mirabilis is identical to that of Paranemertes cf. peregrina, both of which are Hoplonemertea, while that of Z. rubens is the same as in Lineus viridis, both of which are Heteronemertea. Comparison of the gene arrangements and phylogenomic analysis based on concatenated nucleotide sequences of the 12 mitochondrial protein-coding genes revealed that species with closer relationships share more identical gene blocks. Conclusion The two new mitochondrial genomes share many features, including gene contents, with other known nemertean mitochondrial genomes. The tRNA families display a composite substitution pathway. Gene order comparison to the proposed ground pattern of

  6. A comparative study of nemertean complete mitochondrial genomes, including two new ones for Nectonemertes cf. mirabilis and Zygeupolia rubens, may elucidate the fundamental pattern for the phylum Nemertea.

    Science.gov (United States)

    Chen, Hai-Xia; Sun, Shi-Chun; Sundberg, Per; Ren, Wei-Cheng; Norenburg, Jon L

    2012-04-17

    The mitochondrial genome is important for studying genome evolution as well as reconstructing the phylogeny of organisms. Complete mitochondrial genome sequences have been reported for more than 2200 metazoans, mainly vertebrates and arthropods. To date, from a total of about 1275 described nemertean species, only three complete and two partial mitochondrial DNA sequences from nemerteans have been published. Here, we report the entire mitochondrial genomes for two more nemertean species: Nectonemertes cf. mirabilis and Zygeupolia rubens. The sizes of the entire mitochondrial genomes are 15365 bp for N. cf. mirabilis and 15513 bp for Z. rubens. Each circular genome contains 37 genes and an AT-rich non-coding region, and overall nucleotide composition is AT-rich. In both species, there is significant strand asymmetry in the distribution of nucleotides, with the coding strand being richer in T than A and in G than C. The AT-rich non-coding regions of the two genomes have some repeat sequences and stem-loop structures, both of which may be associated with the initiation of replication or transcription. The 22 tRNAs show variable substitution patterns in nemerteans, with higher sequence conservation in genes located on the H strand. Gene arrangement of N. cf. mirabilis is identical to that of Paranemertes cf. peregrina, both of which are Hoplonemertea, while that of Z. rubens is the same as in Lineus viridis, both of which are Heteronemertea. Comparison of the gene arrangements and phylogenomic analysis based on concatenated nucleotide sequences of the 12 mitochondrial protein-coding genes revealed that species with closer relationships share more identical gene blocks. The two new mitochondrial genomes share many features, including gene contents, with other known nemertean mitochondrial genomes. The tRNA families display a composite substitution pathway. Gene order comparison to the proposed ground pattern of Bilateria and some lophotrochozoans suggests that the

  7. Genomic analyses and transcriptional profiles of the glycoside hydrolase family 18 genes of the entomopathogenic fungus Metarhizium anisopliae.

    Science.gov (United States)

    Junges, Ângela; Boldo, Juliano Tomazzoni; Souza, Bárbara Kunzler; Guedes, Rafael Lucas Muniz; Sbaraini, Nicolau; Kmetzsch, Lívia; Thompson, Claudia Elizabeth; Staats, Charley Christian; de Almeida, Luis Gonzaga Paula; de Vasconcelos, Ana Tereza Ribeiro; Vainstein, Marilene Henning; Schrank, Augusto

    2014-01-01

    Fungal chitin metabolism involves diverse processes such as metabolically active cell wall maintenance, basic nutrition, and different aspects of virulence. Chitinases are enzymes belonging to the glycoside hydrolase family 18 (GH18) and 19 (GH19) and are responsible for the hydrolysis of β-1,4-linkages in chitin. This linear homopolymer of N-acetyl-β-D-glucosamine is an essential constituent of fungal cell walls and arthropod exoskeletons. Several chitinases have been directly implicated in structural, morphogenetic, autolytic and nutritional activities of fungal cells. In the entomopathogen Metarhizium anisopliae, chitinases are also involved in virulence. Filamentous fungi genomes exhibit a higher number of chitinase-coding genes than bacteria or yeasts. The survey performed in the M. anisopliae genome has successfully identified 24 genes belonging to glycoside hydrolase family 18, including three previously experimentally determined chitinase-coding genes named chit1, chi2 and chi3. These putative chitinases were classified based on domain organization and phylogenetic analysis into the previously described A, B and C chitinase subgroups, and into a new subgroup D. Moreover, three GH18 proteins could be classified as putative endo-N-acetyl-β-D-glucosaminidases, enzymes that are associated with deglycosylation and were therefore assigned to a new subgroup E. The transcriptional profile of the GH18 genes was evaluated by qPCR with RNA extracted from eight culture conditions, representing different stages of development or different nutritional states. The transcripts from the GH18 genes were detected in at least one of the different M. anisopliae developmental stages, thus validating the proposed genes. Moreover, not all members from the same chitinase subgroup presented equal patterns of transcript expression under the eight distinct conditions studied. The determination of M. anisopliae chitinases and ENGases and a more detailed study concerning the enzymes

  8. Genomic analyses and transcriptional profiles of the glycoside hydrolase family 18 genes of the entomopathogenic fungus Metarhizium anisopliae.

    Directory of Open Access Journals (Sweden)

    Ângela Junges

    Full Text Available Fungal chitin metabolism involves diverse processes such as metabolically active cell wall maintenance, basic nutrition, and different aspects of virulence. Chitinases are enzymes belonging to the glycoside hydrolase family 18 (GH18 and 19 (GH19 and are responsible for the hydrolysis of β-1,4-linkages in chitin. This linear homopolymer of N-acetyl-β-D-glucosamine is an essential constituent of fungal cell walls and arthropod exoskeletons. Several chitinases have been directly implicated in structural, morphogenetic, autolytic and nutritional activities of fungal cells. In the entomopathogen Metarhizium anisopliae, chitinases are also involved in virulence. Filamentous fungi genomes exhibit a higher number of chitinase-coding genes than bacteria or yeasts. The survey performed in the M. anisopliae genome has successfully identified 24 genes belonging to glycoside hydrolase family 18, including three previously experimentally determined chitinase-coding genes named chit1, chi2 and chi3. These putative chitinases were classified based on domain organization and phylogenetic analysis into the previously described A, B and C chitinase subgroups, and into a new subgroup D. Moreover, three GH18 proteins could be classified as putative endo-N-acetyl-β-D-glucosaminidases, enzymes that are associated with deglycosylation and were therefore assigned to a new subgroup E. The transcriptional profile of the GH18 genes was evaluated by qPCR with RNA extracted from eight culture conditions, representing different stages of development or different nutritional states. The transcripts from the GH18 genes were detected in at least one of the different M. anisopliae developmental stages, thus validating the proposed genes. Moreover, not all members from the same chitinase subgroup presented equal patterns of transcript expression under the eight distinct conditions studied. The determination of M. anisopliae chitinases and ENGases and a more detailed study

  9. Genomic and Transcriptomic Analyses of Colistin-Resistant Clinical Isolates of Klebsiella pneumoniae Reveal Multiple Pathways of Resistance

    Science.gov (United States)

    Wright, Meredith S.; Suzuki, Yo; Jones, Marcus B.; Marshall, Steven H.; Rudin, Susan D.; van Duin, David; Kaye, Keith; Jacobs, Michael R.

    2014-01-01

    The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae has resulted in a more frequent reliance on treatment using colistin. However, resistance to colistin (Colr) is increasingly reported from clinical settings. The genetic mechanisms that lead to Colr in K. pneumoniae are not fully characterized. Using a combination of genome sequencing and transcriptional profiling by RNA sequencing (RNA-Seq) analysis, distinct genetic mechanisms were found among nine Colr clinical isolates. Colr was related to mutations in three different genes in K. pneumoniae strains, with distinct impacts on gene expression. Upregulation of the pmrH operon encoding 4-amino-4-deoxy-l-arabinose (Ara4N) modification of lipid A was found in all Colr strains. Alteration of the mgrB gene was observed in six strains. One strain had a mutation in phoQ. Common among these seven strains was elevated expression of phoPQ and unaltered expression of pmrCAB, which is involved in phosphoethanolamine addition to lipopolysaccharide (LPS). In two strains, separate mutations were found in a previously uncharacterized histidine kinase gene that is part of a two-component regulatory system (TCRS) now designated crrAB. In these strains, expression of pmrCAB, crrAB, and an adjacent glycosyltransferase gene, but not that of phoPQ, was elevated. Complementation with the wild-type allele restored colistin susceptibility in both strains. The crrAB genes are present in most K. pneumoniae genomes, but not in Escherichia coli. Additional upregulated genes in all strains include those involved in cation transport and maintenance of membrane integrity. Because the crrAB genes are present in only some strains, Colr mechanisms may be dependent on the genetic background. PMID:25385117

  10. Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood.

    Science.gov (United States)

    Chan, Wing Keung; Rujkijyanont, Piya; Neale, Geoffrey; Yang, Jie; Bari, Rafijul; Das Gupta, Neha; Holladay, Martha; Rooney, Barbara; Leung, Wing

    2013-08-15

    Killer cell Ig-like receptors (KIRs) on NK cells have been linked to a wide spectrum of health conditions such as chronic infections, autoimmune diseases, pregnancy complications, cancers, and transplant failures. A small subset of effector memory T cells also expresses KIRs. In this study, we use modern analytic tools including genome-wide and multiplex molecular, phenotypic, and functional assays to characterize the KIR(+) T cells in human blood. We find that KIR(+) T cells primarily reside in the CD56(+) T population that is distinctively DNAM-1(high) with a genome-wide quiescent transcriptome, short telomere, and limited TCR excision circles. During CMV reactivation in bone marrow transplant recipients, KIR(+)CD56(+) T cells rapidly expanded in real-time but not KIR(+)CD56(-) T cells or KIR(+) NK cells. In CMV(+) asymptomatic donors, as much as 50% of CD56(+) T cells are KIR(+), and most are distinguishably KIR2DL2/3(+)NKG2C(+)CD57(+). Functionally, the KIR(+)CD56(+) T cell subset lyses cancer cells and CMVpp65-pulsed target cells in a dual KIR-dependent and TCR-dependent manner. Analysis of metabolic transcriptome confirms the immunological memory status of KIR(+)CD56(+) T cells in contrast to KIR(-)CD56(+) T cells that are more active in energy metabolism and effector differentiation. KIR(-)CD56(+) T cells have >25-fold higher level of expression of RORC than the KIR(+) counterpart and are a previously unknown producer of IL-13 rather than IL-17 in multiplex cytokine arrays. Our data provide fundamental insights into KIR(+) T cells biologically and clinically.

  11. Estimation of the Whitefly Bemisia tabaci Genome Size Based on k-mer and Flow Cytometric Analyses

    Directory of Open Access Journals (Sweden)

    Wenbo Chen

    2015-07-01

    Full Text Available Whiteflies of the Bemisia tabaci (Hemiptera: Aleyrodidae cryptic species complex are among the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 1000 species of plants worldwide and inflict severe economic losses to crops, mainly through the transmission of pathogenic viruses. Surprisingly, there is very little genomic information about whiteflies. As a starting point to genome sequencing, we report a new estimation of the genome size of the B. tabaci B biotype or Middle East-Asia Minor 1 (MEAM1 population. Using an isogenic whitefly colony with over 6500 haploid male individuals for genomic DNA, three paired-end genomic libraries with insert sizes of ~300 bp, 500 bp and 1 Kb were constructed and sequenced on an Illumina HiSeq 2500 system. A total of ~50 billion base pairs of sequences were obtained from each library. K-mer analysis using these sequences revealed that the genome size of the whitefly was ~682.3 Mb. In addition, the flow cytometric analysis estimated the haploid genome size of the whitefly to be ~690 Mb. Considering the congruency between both estimation methods, we predict the haploid genome size of B. tabaci MEAM1 to be ~680–690 Mb. Our data provide a baseline for ongoing efforts to assemble and annotate the B. tabaci genome.

  12. Horizontal gene transfer in Histophilus somni and its role in the evolution of pathogenic strain 2336, as determined by comparative genomic analyses

    Directory of Open Access Journals (Sweden)

    Siddaramappa Shivakumara

    2011-11-01

    Full Text Available Abstract Background Pneumonia and myocarditis are the most commonly reported diseases due to Histophilus somni, an opportunistic pathogen of the reproductive and respiratory tracts of cattle. Thus far only a few genes involved in metabolic and virulence functions have been identified and characterized in H. somni using traditional methods. Analyses of the genome sequences of several Pasteurellaceae species have provided insights into their biology and evolution. In view of the economic and ecological importance of H. somni, the genome sequence of pneumonia strain 2336 has been determined and compared to that of commensal strain 129Pt and other members of the Pasteurellaceae. Results The chromosome of strain 2336 (2,263,857 bp contained 1,980 protein coding genes, whereas the chromosome of strain 129Pt (2,007,700 bp contained only 1,792 protein coding genes. Although the chromosomes of the two strains differ in size, their average GC content, gene density (total number of genes predicted on the chromosome, and percentage of sequence (number of genes that encodes proteins were similar. The chromosomes of these strains also contained a number of discrete prophage regions and genomic islands. One of the genomic islands in strain 2336 contained genes putatively involved in copper, zinc, and tetracycline resistance. Using the genome sequence data and comparative analyses with other members of the Pasteurellaceae, several H. somni genes that may encode proteins involved in virulence (e.g., filamentous haemaggutinins, adhesins, and polysaccharide biosynthesis/modification enzymes were identified. The two strains contained a total of 17 ORFs that encode putative glycosyltransferases and some of these ORFs had characteristic simple sequence repeats within them. Most of the genes/loci common to both the strains were located in different regions of the two chromosomes and occurred in opposite orientations, indicating genome rearrangement since their

  13. Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans

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    Kwang-Woo Jung

    2016-11-01

    Full Text Available The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans.

  14. Phylogenomic and structural analyses of 18 complete plastomes across nearly all families of early-diverging eudicots, including an angiosperm-wide analysis of IR gene content evolution.

    Science.gov (United States)

    Sun, Yanxia; Moore, Michael J; Zhang, Shoujun; Soltis, Pamela S; Soltis, Douglas E; Zhao, Tingting; Meng, Aiping; Li, Xiaodong; Li, Jianqiang; Wang, Hengchang

    2016-03-01

    The grade of early-diverging eudicots includes five major lineages: Ranunculales, Trochodendrales, Buxales, Proteales and Sabiaceae. To examine the evolution of plastome structure in early-diverging eudicots, we determined the complete plastome sequences of eight previously unsequenced early-diverging eudicot taxa, Pachysandra terminalis (Buxaceae), Meliosma aff. cuneifolia (Sabiaceae), Sabia yunnanensis (Sabiaceae), Epimedium sagittatum (Berberidaceae), Euptelea pleiosperma (Eupteleaceae), Akebia trifoliata (Lardizabalaceae), Stephania japonica (Menispermaceae) and Papaver somniferum (Papaveraceae), and compared them to previously published plastomes of the early-diverging eudicots Buxus, Tetracentron, Trochodendron, Nelumbo, Platanus, Nandina, Megaleranthis, Ranunculus, Mahonia and Macadamia. All of the newly sequenced plastomes share the same 79 protein-coding genes, 4 rRNA genes, and 30 tRNA genes, except for that of Epimedium, in which infA is pseudogenized and clpP is highly divergent and possibly a pseudogene. The boundaries of the plastid Inverted Repeat (IR) were found to vary significantly across early-diverging eudicots; IRs ranged from 24.3 to 36.4kb in length and contained from 18 to 33 genes. Based on gene content, the IR was classified into six types, with shifts among types characterized by high levels of homoplasy. Reconstruction of ancestral IR gene content suggested that 18 genes were likely present in the IR region of the ancestor of eudicots. Maximum likelihood phylogenetic analysis of a 79-gene, 97-taxon data set that included all available early-diverging eudicots and representative sampling of remaining angiosperm diversity largely agreed with previous estimates of early-diverging eudicot relationships, but resolved Trochodendrales rather than Buxales as sister to Gunneridae, albeit with relatively weak bootstrap support, conflicting with what has been found for these three clades in most previous analyses. In addition, Proteales was

  15. Ecophysiological significance of scale-dependent patterns in prokaryotic genomes unveiled by a combination of statistic and genometric analyses.

    Science.gov (United States)

    Garcia, Juan A L; Bartumeus, Frederic; Roche, David; Giraldo, Jesús; Stanley, H Eugene; Casamayor, Emilio O

    2008-06-01

    We combined genometric (DNA walks) and statistical (detrended fluctuation analysis) methods on 456 prokaryotic chromosomes from 309 different bacterial and archaeal species to look for specific patterns and long-range correlations along the genome and relate them to ecological lifestyles. The position of each nucleotide along the complete genome sequence was plotted on an orthogonal plane (DNA landscape), and fluctuation analysis applied to the DNA walk series showed a long-range correlation in contrast to the lack of correlation for artificially generated genomes. Different features in the DNA landscapes among genomes from different ecological and metabolic groups of prokaryotes appeared with the combined analysis. Transition from hyperthermophilic to psychrophilic environments could have been related to more complex structural adaptations in microbial genomes, whereas for other environmental factors such as pH and salinity this effect would have been smaller. Prokaryotes with domain-specific metabolisms, such as photoautotrophy in Bacteria and methanogenesis in Archaea, showed consistent differences in genome correlation structure. Overall, we show that, beyond the relative proportion of nucleotides, correlation properties derived from their sequential position within the genome hide relevant phylogenetic and ecological information. This can be studied by combining genometric and statistical physics methods, leading to a reduction of genome complexity to a few useful descriptors.

  16. Genome analyses of the sunflower pathogen Plasmopara halstedii provide insights into effector evolution in downy mildews and Phytophthora

    NARCIS (Netherlands)

    Sharma, Rahul; Xia, Xiaojuan; Cano, Liliana M; Evangelisti, Edouard; Kemen, Eric; Judelson, Howard; Oome, Stan; Sambles, Christine; van den Hoogen, D Johan; Kitner, Miloslav; Klein, Joël; Meijer, Harold J G; Spring, Otmar; Win, Joe; Zipper, Reinhard; Bode, Helge B; Govers, Francine; Kamoun, Sophien; Schornack, Sebastian; Studholme, David J; Van den Ackerveken, Guido; Thines, Marco

    2015-01-01

    BACKGROUND: Downy mildews are the most speciose group of oomycetes and affect crops of great economic importance. So far, there is only a single deeply-sequenced downy mildew genome available, from Hyaloperonospora arabidopsidis. Further genomic resources for downy mildews are required to study thei

  17. Whole genome sequence analysis of circulating Bluetongue virus serotype 11 strains from the United States including two domestic canine isolates.

    Science.gov (United States)

    Gaudreault, Natasha N; Jasperson, Dane C; Dubovi, Edward J; Johnson, Donna J; Ostlund, Eileen N; Wilson, William C

    2015-07-01

    Bluetongue virus (BTV) is a vector-transmitted pathogen that typically infects and causes disease in domestic and wild ruminants. BTV is also known to infect domestic canines as discovered when dogs were vaccinated with a BTV-contaminated vaccine. Canine BTV infections have been documented through serological surveys, and natural infection by the Culicoides vector has been suggested. The report of isolation of BTV serotype 11 (BTV-11) from 2 separate domestic canine abortion cases in the states of Texas in 2011 and Kansas in 2012, were apparently unrelated to BTV-contaminated vaccination or consumption of BTV-contaminated raw meat as had been previously speculated. To elucidate the origin and relationship of these 2 domestic canine BTV-11 isolates, whole genome sequencing was performed. Six additional BTV-11 field isolates from Texas, Florida, and Washington, submitted for diagnostic investigation during 2011 and 2013, were also fully sequenced and analyzed. The phylogenetic analysis indicates that the BTV-11 domestic canine isolates are virtually identical, and both share high identity with 2 BTV-11 isolates identified from white-tailed deer in Texas in 2011. The results of the current study further support the hypothesis that a BTV-11 strain circulating in the Midwestern states could have been transmitted to the dogs by the infected Culicoides vector. Our study also expands the short list of available BTV-11 sequences, which may aid BTV surveillance and epidemiology.

  18. Genome-scale data suggest reclassifications in the Leisingera-Phaeobacter cluster including proposals for Sedimentitalea gen. nov. and Pseudophaeobacter gen. nov.

    Science.gov (United States)

    Breider, Sven; Scheuner, Carmen; Schumann, Peter; Fiebig, Anne; Petersen, Jörn; Pradella, Silke; Klenk, Hans-Peter; Brinkhoff, Thorsten; Göker, Markus

    2014-01-01

    Earlier phylogenetic analyses of the marine Rhodobacteraceae (class Alphaproteobacteria) genera Leisingera and Phaeobacter indicated that neither genus might be monophyletic. We here used phylogenetic reconstruction from genome-scale data, MALDI-TOF mass-spectrometry analysis and a re-assessment of the phenotypic data from the literature to settle this matter, aiming at a reclassification of the two genera. Neither Phaeobacter nor Leisingera formed a clade in any of the phylogenetic analyses conducted. Rather, smaller monophyletic assemblages emerged, which were phenotypically more homogeneous, too. We thus propose the reclassification of Leisingera nanhaiensis as the type species of a new genus as Sedimentitalea nanhaiensis gen. nov., comb. nov., the reclassification of Phaeobacter arcticus and Phaeobacter leonis as Pseudophaeobacter arcticus gen. nov., comb. nov. and Pseudophaeobacter leonis comb. nov., and the reclassification of Phaeobacter aquaemixtae, Phaeobacter caeruleus, and Phaeobacter daeponensis as Leisingera aquaemixtae comb. nov., Leisingera caerulea comb. nov., and Leisingera daeponensis comb. nov. The genera Phaeobacter and Leisingera are accordingly emended.

  19. Characterization of Sinorhizobium sp. LM21 Prophages and Virus-Encoded DNA Methyltransferases in the Light of Comparative Genomic Analyses of the Sinorhizobial Virome.

    Science.gov (United States)

    Decewicz, Przemyslaw; Radlinska, Monika; Dziewit, Lukasz

    2017-06-26

    The genus Sinorhizobium/Ensifer mostly groups nitrogen-fixing bacteria that create root or stem nodules on leguminous plants and transform atmospheric nitrogen into ammonia, which improves the productivity of the plants. Although these biotechnologically-important bacteria are commonly found in various soil environments, little is known about their phages. In this study, the genome of Sinorhizobium sp. LM21 isolated from a heavy-metal-contaminated copper mine in Poland was investigated for the presence of prophages and DNA methyltransferase-encoding genes. In addition to the previously identified temperate phage, ΦLM21, and the phage-plasmid, pLM21S1, the analysis revealed the presence of three prophage regions. Moreover, four novel phage-encoded DNA methyltransferase (MTase) genes were identified and the enzymes were characterized. It was shown that two of the identified viral MTases methylated the same target sequence (GANTC) as cell cycle-regulated methyltransferase (CcrM) of the bacterial host strain, LM21. This discovery was recognized as an example of the evolutionary convergence between enzymes of sinorhizobial viruses and their host, which may play an important role in virus cycle. In the last part of the study, thorough comparative analyses of 31 sinorhizobial (pro)phages (including active sinorhizobial phages and novel putative prophages retrieved and manually re-annotated from Sinorhizobium spp. genomes) were performed. The networking analysis revealed the presence of highly conserved proteins (e.g., holins and endolysins) and a high diversity of viral integrases. The analysis also revealed a large number of viral DNA MTases, whose genes were frequently located within the predicted replication modules of analyzed prophages, which may suggest their important regulatory role. Summarizing, complex analysis of the phage protein similarity network enabled a new insight into overall sinorhizobial virome diversity.

  20. Genome-wide analyses of chitin synthases identify horizontal gene transfers towards bacteria and allow a robust and unifying classification into fungi.

    Science.gov (United States)

    Gonçalves, Isabelle R; Brouillet, Sophie; Soulié, Marie-Christine; Gribaldo, Simonetta; Sirven, Catherine; Charron, Noémie; Boccara, Martine; Choquer, Mathias

    2016-11-24

    Chitin, the second most abundant biopolymer on earth after cellulose, is found in probably all fungi, many animals (mainly invertebrates), several protists and a few algae, playing an essential role in the development of many of them. This polysaccharide is produced by type 2 glycosyltransferases, called chitin synthases (CHS). There are several contradictory classifications of CHS isoenzymes and, as regards their evolutionary history, their origin and diversity is still a matter of debate. A genome-wide analysis resulted in the detection of more than eight hundred putative chitin synthases in proteomes associated with about 130 genomes. Phylogenetic analyses were performed with special care to avoid any pitfalls associated with the peculiarities of these sequences (e.g. highly variable regions, truncated or recombined sequences, long-branch attraction). This allowed us to revise and unify the fungal CHS classification and to study the evolutionary history of the CHS multigenic family. This update has the advantage of being user-friendly due to the development of a dedicated website ( http://wwwabi.snv.jussieu.fr/public/CHSdb ), and it includes any correspondences with previously published classifications and mutants. Concerning the evolutionary history of CHS, this family has mainly evolved via duplications and losses. However, it is likely that several horizontal gene transfers (HGT) also occurred in eukaryotic microorganisms and, even more surprisingly, in bacteria. This comprehensive multi-species analysis contributes to the classification of fungal CHS, in particular by optimizing its robustness, consensuality and accessibility. It also highlights the importance of HGT in the evolutionary history of CHS and describes bacterial chs genes for the first time. Many of the bacteria that have acquired a chitin synthase are plant pathogens (e.g. Dickeya spp; Pectobacterium spp; Brenneria spp; Agrobacterium vitis and Pseudomonas cichorii). Whether they are able to

  1. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

    OpenAIRE

    Randall, J. C.; Winkler, T.W.; Kutalik, Z.; Berndt, S.I.; Jackson, A.U.; Monda, K.L.; Kilpelainen, T.O.; Esko, T; Magi, R.; Li, S.; Workalemahu, T; Feitosa,M. F.; Croteau-Chonka, D.C.; Day, F. R.; Fall, T.

    2013-01-01

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previousl...

  2. Statistical methods for meta-analyses including information from studies without any events-add nothing to nothing and succeed nevertheless.

    Science.gov (United States)

    Kuss, O

    2015-03-30

    Meta-analyses with rare events, especially those that include studies with no event in one ('single-zero') or even both ('double-zero') treatment arms, are still a statistical challenge. In the case of double-zero studies, researchers in general delete these studies or use continuity corrections to avoid them. A number of arguments against both options has been given, and statistical methods that use the information from double-zero studies without using continuity corrections have been proposed. In this paper, we collect them and compare them by simulation. This simulation study tries to mirror real-life situations as completely as possible by deriving true underlying parameters from empirical data on actually performed meta-analyses. It is shown that for each of the commonly encountered effect estimators valid statistical methods are available that use the information from double-zero studies without using continuity corrections. Interestingly, all of them are truly random effects models, and so also the current standard method for very sparse data as recommended from the Cochrane collaboration, the Yusuf-Peto odds ratio, can be improved on. For actual analysis, we recommend to use beta-binomial regression methods to arrive at summary estimates for the odds ratio, the relative risk, or the risk difference. Methods that ignore information from double-zero studies or use continuity corrections should no longer be used. We illustrate the situation with an example where the original analysis ignores 35 double-zero studies, and a superior analysis discovers a clinically relevant advantage of off-pump surgery in coronary artery bypass grafting. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Regular exercise participation improves genomic stability in diabetic patients: an exploratory study to analyse telomere length and DNA damage.

    Science.gov (United States)

    Dimauro, Ivan; Sgura, Antonella; Pittaluga, Monica; Magi, Fiorenza; Fantini, Cristina; Mancinelli, Rosa; Sgadari, Antonio; Fulle, Stefania; Caporossi, Daniela

    2017-06-23

    Physical activity has been demonstrated to be effective in the prevention and treatment of different chronic conditions, including type 2 diabetes (T2D). In particular, several studies highlighted how the beneficial effects of physical activity may be related to the stability of the DNA molecule, such as longer telomeric ends. Here we analyze the effect of exercise training on telomere length, spontaneous and H2O2-induced DNA damage, as well as the apoptosis level in leukocytes from untrained or trained T2D patients vs. age-matched control subjects (CS) (57-66 years). Moreover, expression analysis of selected genes belonging to DNA repair systems, cell cycle control, antioxidant and defence systems was performed. Subjects that participated in a regular exercise program showed a longer telomere sequence than untrained counterparts. Moreover, ex vivo treatment of leukocytes with H2O2 highlighted that: (1) oxidative DNA damage induced similar telomere attrition in all groups; (2) in T2D subjects, physical activity seemed to prevent a significant increase of genomic oxidative DNA damage induced by chronic exposure to pro-oxidant stimulus, and (3) decreased the sensitivity of leukocytes to apoptosis. Finally, the gene expression analysis in T2D subjects suggested an adaptive response to prolonged exercise training that improved the response of specific genes.

  4. Differential gene expression from genome-wide microarray analyses distinguishes Lohmann Selected Leghorn and Lohmann Brown layers.

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    Christin Habig

    Full Text Available The Lohmann Selected Leghorn (LSL and Lohmann Brown (LB layer lines have been selected for high egg production since more than 50 years and belong to the worldwide leading commercial layer lines. The objectives of the present study were to characterize the molecular processes that are different among these two layer lines using whole genome RNA expression profiles. The hens were kept in the newly developed small group housing system Eurovent German with two different group sizes. Differential expression was observed for 6,276 microarray probes (FDR adjusted P-value <0.05 among the two layer lines LSL and LB. A 2-fold or greater change in gene expression was identified on 151 probe sets. In LSL, 72 of the 151 probe sets were up- and 79 of them were down-regulated. Gene ontology (GO enrichment analysis accounting for biological processes evinced 18 GO-terms for the 72 probe sets with higher expression in LSL, especially those taking part in immune system processes and membrane organization. A total of 32 enriched GO-terms were determined among the 79 down-regulated probe sets of LSL. Particularly, these terms included phosphorus metabolic processes and signaling pathways. In conclusion, the phenotypic differences among the two layer lines LSL and LB are clearly reflected in their gene expression profiles of the cerebrum. These novel findings provide clues for genes involved in economically important line characteristics of commercial laying hens.

  5. Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

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    Fry Rebecca C

    2011-04-01

    Full Text Available Abstract Background Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored. Results In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis. Conclusions This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.

  6. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete;

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

  7. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

  8. Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males.

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    Yao-Zhong Liu

    Full Text Available BACKGROUND: Current genome-wide association studies (GWAS are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. PRINCIPAL FINDINGS: To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI, with the osteoporosis risk phenotype, hip bone mineral density (BMD, scanning approximately 380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6 gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82x10(-7 and 1.47x10(-6, respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the approximately 380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS cohort containing 3,355 Caucasians (1,370 males and 1,985 females from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. CONCLUSIONS: Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis.

  9. Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2.

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    Sanaa A Ahmed

    Full Text Available In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in Europe which was notable for its high prevalence of hemolytic uremic syndrome cases. Several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical E. coli O104:H4 isolates using draft genome assemblies. We present the complete, closed genome sequences of an isolate from the 2011 outbreak (2011C-3493 and two isolates from cases of bloody diarrhea that occurred in the Republic of Georgia in 2009 (2009EL-2050 and 2009EL-2071. Comparative genome analysis indicates that, while the Georgian strains are the nearest neighbors to the 2011 outbreak isolates sequenced to date, structural and nucleotide-level differences are evident in the Stx2 phage genomes, the mer/tet antibiotic resistance island, and in the prophage and plasmid profiles of the strains, including a previously undescribed plasmid with homology to the pMT virulence plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that 2009EL-2071 possessed higher resistance to polymyxin and membrane-disrupting agents. Finally, we show evidence by electron microscopy of the presence of a common phage morphotype among the European and Georgian strains and a second phage morphotype among the Georgian strains. The presence of at least two stx2 phage genotypes in host genetic backgrounds that may derive from a recent common ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage-containing E. coli O104:H4 strains probably occurred more than once, or that the current outbreak isolates may be the result of a recent transfer of a new stx2 phage element into a pre-existing stx2-positive genetic background.

  10. Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.

    Science.gov (United States)

    Nishimura, Yasuharu; Tomita, Yusuke; Yuno, Akira; Yoshitake, Yoshihiro; Shinohara, Masanori

    2015-05-01

    Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.

  11. Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder.

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    Md Suhail Alam

    Full Text Available Niemann-Pick Type C (NPC disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and a lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional, neurological lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1(-/- mice relative to Npc1(+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates of neurological and/or liver disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gaucher's disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1(-/- as well as Balb/c Npc1(nmf164 mice (bearing a point mutation closer to human disease mutants and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1(-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry. These data revealed neutrophil elevation in the Npc1(-/- spleen and liver (where large foci were detected proximal to damaged tissue. Together our results yield a set of lysosomal, secretory innate immunity genes that have potential to be developed as pan or specific plasma markers for neurological diseases associated with lysosomal storage and where diagnosis is a major problem. Further, the accumulation of neutrophils in diseased organs

  12. Genome Sequence and Transcriptome Analyses of Chrysochromulina tobin: Metabolic Tools for Enhanced Algal Fitness in the Prominent Order Prymnesiales (Haptophyceae.

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    Blake T Hovde

    Full Text Available Haptophytes are recognized as seminal players in aquatic ecosystem function. These algae are important in global carbon sequestration, form destructive harmful blooms, and given their rich fatty acid content, serve as a highly nutritive food source to a broad range of eco-cohorts. Haptophyte dominance in both fresh and marine waters is supported by the mixotrophic nature of many taxa. Despite their importance the nuclear genome sequence of only one haptophyte, Emiliania huxleyi (Isochrysidales, is available. Here we report the draft genome sequence of Chrysochromulina tobin (Prymnesiales, and transcriptome data collected at seven time points over a 24-hour light/dark cycle. The nuclear genome of C. tobin is small (59 Mb, compact (∼ 40% of the genome is protein coding and encodes approximately 16,777 genes. Genes important to fatty acid synthesis, modification, and catabolism show distinct patterns of expression when monitored over the circadian photoperiod. The C. tobin genome harbors the first hybrid polyketide synthase/non-ribosomal peptide synthase gene complex reported for an algal species, and encodes potential anti-microbial peptides and proteins involved in multidrug and toxic compound extrusion. A new haptophyte xanthorhodopsin was also identified, together with two "red" RuBisCO activases that are shared across many algal lineages. The Chrysochromulina tobin genome sequence provides new information on the evolutionary history, ecology and economic importance of haptophytes.

  13. Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits.

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    Simone Marcelletti

    Full Text Available The European hazelnut (Corylus avellana is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches.

  14. Comparative genomic analysis identifies divergent genomic features of pathogenic Enterococcus cecorum including a type IC CRISPR-Cas system, a capsule locus, an epa-like locus, and putative host tissue binding proteins.

    Science.gov (United States)

    Borst, Luke B; Suyemoto, M Mitsu; Scholl, Elizabeth H; Fuller, Fredrick J; Barnes, H John

    2015-01-01

    Enterococcus cecorum (EC) is the dominant enteric commensal of adult chickens and contributes to the gut consortia of many avian and mammalian species. While EC infection is an uncommon zoonosis, like other enterococcal species it can cause life-threating nosocomial infection in people. In contrast to other enterococci which are considered opportunistic pathogens, emerging pathogenic strains of EC cause outbreaks of musculoskeletal disease in broiler chickens. Typical morbidity and mortality is comparable to other important infectious diseases of poultry. In molecular epidemiologic studies, pathogenic EC strains were found to be genetically clonal. These findings suggested acquisition of specific virulence determinants by pathogenic EC. To identify divergent genomic features and acquired virulence determinants in pathogenic EC; comparative genomic analysis was performed on genomes of 3 pathogenic and 3 commensal strains of EC. Pathogenic isolates had smaller genomes with a higher GC content, and they demonstrated large regions of synteny compared to commensal isolates. A molecular phylogenetic analysis demonstrated sequence divergence in pathogenic EC genomes. At a threshold of 98% identity, 414 predicted proteins were identified that were highly conserved in pathogenic EC but not in commensal EC. Among these, divergent CRISPR-cas defense loci were observed. In commensal EC, the type IIA arrangement typical for enterococci was present; however, pathogenic EC had a type IC locus, which is novel in enterococci but commonly observed in streptococci. Potential mediators of virulence identified in this analysis included a polysaccharide capsular locus similar to that recently described for E. faecium, an epa-like locus, and cell wall associated proteins which may bind host extracellular matrix. This analysis identified specific genomic regions, coding sequences, and predicted proteins which may be related to the divergent evolution and increased virulence of emerging

  15. Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data.

    Science.gov (United States)

    Hyland, Paula L; Zhang, Han; Yang, Qi; Yang, Howard H; Hu, Nan; Lin, Shih-Wen; Su, Hua; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Fan, Jin-Hu; Qiao, You-Lin; Sung, Hyuna; Wheeler, William; Giffen, Carol; Burdett, Laurie; Wang, Zhaoming; Lee, Maxwell P; Chanock, Stephen J; Dawsey, Sanford M; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Yu, Kai; Taylor, Philip R

    2016-02-01

    Oesophageal cancer is the fourth leading cause of cancer death in China where essentially all cases are histologically oesophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses of genome-wide association study (GWAS) data combined with tissue-specific expression quantitative trait loci (eQTL) analysis and publicly available functional data can identify biological pathways and/or genes enriched with functionally-relevant disease-associated variants. We used the adaptive multilocus joint test to analyse 1827 pathways containing 6060 genes using GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. We examined the function of risk alleles using in silico and eQTL analyses in oesophageal tissues. Associations with ESCC risk were observed for 36 pathways predominantly involved in apoptosis, cell cycle regulation and DNA repair and containing known GWAS-associated genes. After excluding genes with previous GWAS signals, candidate pathways (and genes) for ESCC risk included taste transduction (KEGG_hsa04742; TAS2R13, TAS2R42, TAS2R14, TAS2R46,TAS2R50), long-patch base excision repair (Reactome_pid; POLD2) and the metabolics pathway (KEGG_hsa01100; MTAP, GAPDH, DCTD, POLD2, AMDHD1). We identified and validated CASP8 rs13016963 and IDH2 rs11630814 as eQTLs, and CASP8 rs3769823 and IDH2 rs4561444 as the potential functional variants in high-linkage disequilibrium with these single nucleotide polymorphisms (SNPs), respectively. Further, IDH2 mRNA levels were down-regulated in ESCC (tumour:normal-fold change = 0.69, P =  .75E-14). Agnostic pathway-based analyses and integration of multiple types of functional data provide new evidence for the contribution of genes in taste transduction and metabolism to ESCC susceptibility, and for the functionality of both established and new ESCC risk-related SNPs. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by US Government

  16. Targeted sequencing for high-resolution evolutionary analyses following genome duplication in salmonid fish: Proof of concept for key components of the insulin-like growth factor axis.

    Science.gov (United States)

    Lappin, Fiona M; Shaw, Rebecca L; Macqueen, Daniel J

    2016-12-01

    High-throughput sequencing has revolutionised comparative and evolutionary genome biology. It has now become relatively commonplace to generate multiple genomes and/or transcriptomes to characterize the evolution of large taxonomic groups of interest. Nevertheless, such efforts may be unsuited to some research questions or remain beyond the scope of some research groups. Here we show that targeted high-throughput sequencing offers a viable alternative to study genome evolution across a vertebrate family of great scientific interest. Specifically, we exploited sequence capture and Illumina sequencing to characterize the evolution of key components from the insulin-like growth (IGF) signalling axis of salmonid fish at unprecedented phylogenetic resolution. The IGF axis represents a central governor of vertebrate growth and its core components were expanded by whole genome duplication in the salmonid ancestor ~95Ma. Using RNA baits synthesised to genes encoding the complete family of IGF binding proteins (IGFBP) and an IGF hormone (IGF2), we captured, sequenced and assembled orthologous and paralogous exons from species representing all ten salmonid genera. This approach generated 299 novel sequences, most as complete or near-complete protein-coding sequences. Phylogenetic analyses confirmed congruent evolutionary histories for all nineteen recognized salmonid IGFBP family members and identified novel salmonid-specific IGF2 paralogues. Moreover, we reconstructed the evolution of duplicated IGF axis paralogues across a replete salmonid phylogeny, revealing complex historic selection regimes - both ancestral to salmonids and lineage-restricted - that frequently involved asymmetric paralogue divergence under positive and/or relaxed purifying selection. Our findings add to an emerging literature highlighting diverse applications for targeted sequencing in comparative-evolutionary genomics. We also set out a viable approach to obtain large sets of nuclear genes for any

  17. Genome-wide association mapping including phenotypes from relatives without genotypes in a single-step (ssGWAS for 6-week body weight in broiler chickens

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    Huiyu eWang

    2014-05-01

    Full Text Available The purpose of this study was to compare results obtained from various methodologies for genome-wide association studies, when applied to real data, in terms of number and commonality of regions identified and their genetic variance explained, computational speed, and possible pitfalls in interpretations of results. Methodologies include: two iteratively reweighted single-step genomic BLUP procedures (ssGWAS1 and ssGWAS2, a single-marker model (CGWAS, and BayesB. The ssGWAS methods utilize genomic breeding values (GEBVs based on combined pedigree, genomic and phenotypic information, while CGWAS and BayesB only utilize phenotypes from genotyped animals or pseudo-phenotypes. In this study, ssGWAS was performed by converting GEBVs to SNP marker effects. Unequal variances for markers were incorporated for calculating weights into a new genomic relationship matrix. SNP weights were refined iteratively. The data was body weight at 6 weeks on 274,776 broiler chickens, of which 4553 were genotyped using a 60k SNP chip. Comparison of genomic regions was based on genetic variances explained by local SNP regions (20 SNPs. After 3 iterations, the noise was greatly reduced of ssGWAS1 and results are similar to that of CGWAS, with 4 out of the top 10 regions in common. In contrast, for BayesB, the plot was dominated by a single region explaining 23.1% of the genetic variance. This same region was found by ssGWAS1 with the same rank, but the amount of genetic variation attributed to the region was only 3%. These finding emphasize the need for caution when comparing and interpreting results from various methods, and highlight that detected associations, and strength of association, strongly depends on methodologies and details of implementations. BayesB appears to overly shrink regions to zero, while overestimating the amount of genetic variation attributed to the remaining SNP effects. The real world is most likely a compromise between methods and remains to

  18. Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes.

    Science.gov (United States)

    Frantz, Laurent A F; Schraiber, Joshua G; Madsen, Ole; Megens, Hendrik-Jan; Cagan, Alex; Bosse, Mirte; Paudel, Yogesh; Crooijmans, Richard P M A; Larson, Greger; Groenen, Martien A M

    2015-10-01

    Traditionally, the process of domestication is assumed to be initiated by humans, involve few individuals and rely on reproductive isolation between wild and domestic forms. We analyzed pig domestication using over 100 genome sequences and tested whether pig domestication followed a traditional linear model or a more complex, reticulate model. We found that the assumptions of traditional models, such as reproductive isolation and strong domestication bottlenecks, are incompatible with the genetic data. In addition, our results show that, despite gene flow, the genomes of domestic pigs have strong signatures of selection at loci that affect behavior and morphology. We argue that recurrent selection for domestic traits likely counteracted the homogenizing effect of gene flow from wild boars and created 'islands of domestication' in the genome. Our results have major ramifications for the understanding of animal domestication and suggest that future studies should employ models that do not assume reproductive isolation.

  19. Characterization of the complete mitochondrial genome sequence of Homalogaster paloniae (Gastrodiscidae, Trematoda) and comparative analyses with selected digeneans.

    Science.gov (United States)

    Yang, Xin; Wang, Lixia; Feng, Hanli; Qi, Mingwei; Zhang, Zongze; Gao, Chong; Wang, Chunqun; Hu, Min; Fang, Rui; Li, Chengye

    2016-10-01

    Gastrodiscidae species are neglected but significant paramphistomes in small ruminants, which can lead to considerable economic losses to the breeding industry of livestock. However, knowledge about molecular ecology, population genetics, and phylogenetic analysis is still limited. In the present study, we firstly sequenced and analyzed the full mitochondrial (mt) genome of Homalogaster paloniae (14,490 bp). The gene contents and organization of the H. paloniae mt genome is the same as that of other digeneans, such as Fasciola hepatica and Paramphistomum cervi. It is interesting that unlike other paramphistomes, H. paloniae is flat in shape which is similar with Fasciola, such as F. hepatica. Phylogenetic analysis of H. paloniae and other 17 selected digeneans using concatenated amino acid sequences of the 12 protein-coding genes showed that Gastrodiscidae is closely related to Paramphistomidae and Gastrothylacidae. The availability of the mt genome sequence of H. paloniae should provide an important foundation for further molecular study of Gastrodiscidae and other digeneans.

  20. Effects of Including Misidentified Sharks in Life History Analyses: A Case Study on the Grey Reef Shark Carcharhinus amblyrhynchos from Papua New Guinea.

    Science.gov (United States)

    Smart, Jonathan J; Chin, Andrew; Baje, Leontine; Green, Madeline E; Appleyard, Sharon A; Tobin, Andrew J; Simpfendorfer, Colin A; White, William T

    2016-01-01

    Fisheries observer programs are used around the world to collect crucial information and samples that inform fisheries management. However, observer error may misidentify similar-looking shark species. This raises questions about the level of error that species misidentifications could introduce to estimates of species' life history parameters. This study addressed these questions using the Grey Reef Shark Carcharhinus amblyrhynchos as a case study. Observer misidentification rates were quantified by validating species identifications using diagnostic photographs taken on board supplemented with DNA barcoding. Length-at-age and maturity ogive analyses were then estimated and compared with and without the misidentified individuals. Vertebrae were retained from a total of 155 sharks identified by observers as C. amblyrhynchos. However, 22 (14%) of these were sharks were misidentified by the observers and were subsequently re-identified based on photographs and/or DNA barcoding. Of the 22 individuals misidentified as C. amblyrhynchos, 16 (73%) were detected using photographs and a further 6 via genetic validation. If misidentified individuals had been included, substantial error would have been introduced to both the length-at-age and the maturity estimates. Thus validating the species identification, increased the accuracy of estimated life history parameters for C. amblyrhynchos. From the corrected sample a multi-model inference approach was used to estimate growth for C. amblyrhynchos using three candidate models. The model averaged length-at-age parameters for C. amblyrhynchos with the sexes combined were L∞ = 159 cm TL and L0 = 72 cm TL. Females mature at a greater length (l50 = 136 cm TL) and older age (A50 = 9.1 years) than males (l50 = 123 cm TL; A50 = 5.9 years). The inclusion of techniques to reduce misidentification in observer programs will improve the results of life history studies and ultimately improve management through the use of more accurate data

  1. Core Genome Multilocus Sequence Typing Scheme for Stable, Comparative Analyses of Campylobacter jejuni and C. coli Human Disease Isolates

    Science.gov (United States)

    Bray, James E.; Jolley, Keith A.; McCarthy, Noel D.

    2017-01-01

    ABSTRACT Human campylobacteriosis, caused by Campylobacter jejuni and C. coli, remains a leading cause of bacterial gastroenteritis in many countries, but the epidemiology of campylobacteriosis outbreaks remains poorly defined, largely due to limitations in the resolution and comparability of isolate characterization methods. Whole-genome sequencing (WGS) data enable the improvement of sequence-based typing approaches, such as multilocus sequence typing (MLST), by substantially increasing the number of loci examined. A core genome MLST (cgMLST) scheme defines a comprehensive set of those loci present in most members of a bacterial group, balancing very high resolution with comparability across the diversity of the group. Here we propose a set of 1,343 loci as a human campylobacteriosis cgMLST scheme (v1.0), the allelic profiles of which can be assigned to core genome sequence types. The 1,343 loci chosen were a subset of the 1,643 loci identified in the reannotation of the genome sequence of C. jejuni isolate NCTC 11168, chosen as being present in >95% of draft genomes of 2,472 representative United Kingdom campylobacteriosis isolates, comprising 2,207 (89.3%) C. jejuni isolates and 265 (10.7%) C. coli isolates. Validation of the cgMLST scheme was undertaken with 1,478 further high-quality draft genomes, containing 150 or fewer contiguous sequences, from disease isolate collections: 99.5% of these isolates contained ≥95% of the 1,343 cgMLST loci. In addition to the rapid and effective high-resolution analysis of large numbers of diverse isolates, the cgMLST scheme enabled the efficient identification of very closely related isolates from a well-defined single-source campylobacteriosis outbreak. PMID:28446571

  2. Cytogenetic analyses of eight species in the genus Leptodactylus Fitzinger, 1843 (Amphibia, Anura, Leptodactylidae, including a new diploid number and a karyotype with multiple translocations

    Directory of Open Access Journals (Sweden)

    Gazoni Thiago

    2012-12-01

    Full Text Available Abstract Background The karyotypes of Leptodactylus species usually consist of 22 bi-armed chromosomes, but morphological variations in some chromosomes and even differences in the 2n have been reported. To better understand the mechanisms responsible for these differences, eight species were analysed using classical and molecular cytogenetic techniques, including replication banding with BrdU incorporation. Results Distinct chromosome numbers were found: 2n = 22 in Leptodactylus chaquensis, L. labyrinthicus, L. pentadactylus, L. petersii, L. podicipinus, and L. rhodomystax; 2n = 20 in Leptodactylus sp. (aff. podicipinus; and 2n = 24 in L. marmoratus. Among the species with 2n = 22, only three had the same basic karyotype. Leptodactylus pentadactylus presented multiple translocations, L. petersii displayed chromosome morphological discrepancy, and L. podicipinus had four pairs of telocentric chromosomes. Replication banding was crucial for characterising this variability and for explaining the reduced 2n in Leptodactylus sp. (aff. podicipinus. Leptodactylus marmoratus had few chromosomes with a similar banding patterns to the 2n = 22 karyotypes. The majority of the species presented a single NOR-bearing pair, which was confirmed using Ag-impregnation and FISH with an rDNA probe. In general, the NOR-bearing chromosomes corresponded to chromosome 8, but NORs were found on chromosome 3 or 4 in some species. Leptodactylus marmoratus had NORs on chromosome pairs 6 and 8. The data from C-banding, fluorochrome staining, and FISH using the telomeric probe helped in characterising the repetitive sequences. Even though hybridisation did occur on the chromosome ends, telomere-like repetitive sequences outside of the telomere region were identified. Metaphase I cells from L. pentadactylus confirmed its complex karyotype constitution because 12 chromosomes appeared as ring-shaped chain in addition to five bivalents. Conclusions Species of Leptodactylus

  3. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells

    DEFF Research Database (Denmark)

    Galli, Giorgio Giacomo; Carrara, Matteo; Francavilla, Chiara

    2013-01-01

    find that Prdm5 is highly expressed in mouse embryonic stem cells (mES) and exploit this cellular system to characterize molecular functions of Prdm5. By combining proteomics and next generation sequencing technologies we identify Prdm5 interaction partners and genomic occupancy. We demonstrate that......, despite Prdm5 is dispensable for mES cell maintenance, it directly targets genomic regions involved in early embryonic development and affects the expression of a subset of developmental regulators during cell differentiation. Importantly, Prdm5 interacts with Ctcf, Cohesin and TFIIIC and co...

  4. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    A. Okbay (Aysu); Baselmans, B.M.L. (Bart M.L.); J.E. de Neve (Jan-Emmanuel); P. Turley (Patrick); M. Nivard (Michel); Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); J. Derringer; J. Gratten (Jacob); J.J. Lee (James J.); Liu, J.Z. (Jimmy Z); R. De Vlaming (Ronald); SAhluwalia, T. (Tarunveer); Buchwald, J. (Jadwiga); A. Cavadino (Alana); A.C. Frazier-Wood (Alexis C.); Furlotte, N.A. (Nicholas A); Garfield, V. (Victoria); Geisel, M.H. (Marie Henrike); J.R. Gonzalez (Juan R.); Haitjema, S. (Saskia); R. Karlsson (Robert); Der Laan, S.W. (Sander Wvan); K.-H. Ladwig (Karl-Heinz); J. Lahti (Jari); S. van der Lee (Sven); P.A. Lind (Penelope); Liu, T. (Tian); Matteson, L. (Lindsay); E. Mihailov (Evelin); M. Miller (Mike); CMinica, C. (Camelia); MNolte, I. (Ilja); D.O. Mook-Kanamori (Dennis); P.J. van der Most (Peter); C. Oldmeadow (Christopher); Y. Qian (Yong); O. Raitakari (Olli); R. Rawal (R.); A. Realo; Rueedi, R. (Rico); Schmidt, B. (Börge); A.V. Smith (Albert Vernon); E. Stergiakouli (Evangelia); T. Tanaka (Toshiko); K.D. Taylor (Kent); Wedenoja, J. (Juho); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); MWillems, S. (Sara); Zhao, W. (Wei); L.C. Study (LifeLines Cohort); N. Amin (Najaf); Bakshi, A. (Andrew); P.A. Boyle (Patricia); Cherney, S. (Samantha); Cox, S.R. (Simon R); G. Davies (Gail); O.S.P. Davis (Oliver S.); J. Ding (Jun); N. Direk (Nese); Eibich, P. (Peter); R. Emeny (Rebecca); Fatemifar, G. (Ghazaleh); J.D. Faul; L. Ferrucci (Luigi); A.J. Forstner; C. Gieger (Christian); Gupta, R. (Richa); T.B. Harris (Tamara B.); J.M. Harris (Juliette); E.G. Holliday (Elizabeth); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); M. Kaakinen (Marika); E. Kajantie (Eero); Karhunen, V. (Ville); I. Kolcic (Ivana); M. Kumari (Meena); L.J. Launer (Lenore); L. Franke (Lude); Li-Gao, R. (Ruifang); Koini, M. (Marisa); A. Loukola (Anu); P. Marques-Vidal; G.W. Montgomery (Grant); M. Mosing (Miriam); L. Paternoster (Lavinia); A. Pattie (Alison); K. Petrovic (Katja); Pulkki-R'back, L. (Laura); L. Quaye (Lydia); R'ikkönen, K. (Katri); I. Rudan (Igor); R. Scott (Rodney); J.A. Smith (Jennifer A); A.R. Sutin; Trzaskowski, M. (Maciej); Vinkhuyze, A.E. (Anna E.); L. Yu (Lei); D. Zabaneh (Delilah); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); D.I. Boomsma (Dorret); H. Snieder (Harold); Chang, S.-C. (Shun-Chiao); F. Cucca (Francesco); I.J. Deary (Ian J.); C.M. van Duijn (Cock); K. Hagen (Knut); U. Bültmann (Ute); E.J. Geus (Eeco); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); T. Hansen (T.); Hartman, C.A. (Catharine A); C.M.A. Haworth (Claire M.); C. Hayward (Caroline); A.C. Heath (Andrew C.); D.A. Hinds (David A.); E. Hypponen (Elina); W.G. Iacono (William); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); Keltikangas-J'rvinen, L. (Liisa); P. Kraft (Peter); Kubzansky, L.D. (Laura D.); Lehtim'ki, T. (Terho); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); M. Mills (Melinda); R. de Mutsert (Reneé); A.J. Oldehinkel (Albertine); G. Pasterkamp (Gerard); N.L. Pedersen (Nancy); R. Plomin (Robert); O. Polasek (Ozren); C. Power (Christopher); S.S. Rich (Stephen); F.R. Rosendaal (Frits); H.M. den Ruijter (Hester ); Schlessinger, D. (David); R. Schmidt (Reinhold); R. Svento (Rauli); R. Schmidt (Reinhold); B.Z. Alizadeh (Behrooz); T.I.A. Sørensen (Thorkild); DSpector, T. (Tim); Steptoe, A. (Andrew); A. Terracciano; A.R. Thurik (Roy); N. Timpson (Nicholas); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Vollenweider (Peter); Wagner, G.G. (Gert G.); D.R. Weir (David); J. Yang (Joanna); Conley, D.C. (Dalton C.); G.D. Smith; Hofman, A. (Albert); M. Johannesson (Magnus); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); Pickrell, J.K. (Joseph K.); Esko, T. (T'nu); R.F. Krueger; J.P. Beauchamp (Jonathan); Ph.D. Koellinger (Philipp); D.J. Benjamin (Daniel J.); M. Bartels (Meike); D. Cesarini (David)

    2016-01-01

    textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. W

  5. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz; Sørensen, Thorkild I A; Spector, Tim D; Steptoe, Andrew; Terracciano, Antonio; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  6. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard|info:eu-repo/dai/nl/138488304; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M|info:eu-repo/dai/nl/304123846; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z|info:eu-repo/dai/nl/274070057; Sørensen, Thorkild I A; Spector, Tim D; Steptoe, Andrew; Terracciano, Antonio; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  7. Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes

    NARCIS (Netherlands)

    Frantz, L.A.F.; Schraiber, J.G.; Madsen, O.; Megens, H.J.W.C.; Cagan, A.; Bosse, M.; Paudel, Y.; Crooijmans, R.P.M.A.; Larson, G.; Groenen, M.A.M.

    2015-01-01

    Traditionally, the process of domestication is assumed to be initiated by humans, involve few individuals and rely on reproductive isolation between wild and domestic forms. We analyzed pig domestication using over 100 genome sequences and tested whether pig domestication followed a traditional line

  8. Genomic resources for water yam (Dioscorea alata L.): analyses of EST-Sequences, De Novo sequencing and GBS libraries

    Science.gov (United States)

    The reducing cost and rapid progress in next-generation sequencing techniques coupled with high performance computational approaches have resulted in large-scale discovery of advanced genomic resources such as SSRs, SNPs and InDels in several model and non-model plant species. Yam (Dioscorea spp.) i...

  9. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Science.gov (United States)

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  10. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Vosa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry T. C.; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavac, Metka; Koritnik, Blazi; Zidar, Janez; Leonardis, Lea; Groselj, Leja Dolenc; Millecamps, Stephanie; Salachas, Francois; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-Garcia, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Duerr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Noethen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-Francois; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P.; D'Alfonso, Sandra; Bertolin, Cinzia; Soraru, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Huebner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adrian; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  11. Identification of Novel Drug Targets and Lead Compounds for Advanced Prostate Cancer through Genomic and Cheminformatic Analyses

    Science.gov (United States)

    2015-08-01

    Med Res Rev 2013;33:1081–118. [18] Guo W, Burris TP, Zhang YH, Huang BL, Mason J, Copeland KC, et al. Genomic sequence of the DAX1 gene: an orphan...191] Maran RR, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, et al. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial

  12. Whole genome and global gene expression analyses of the model mushroom Flammulina velutipes reveal a high capacity for lignocellulose degradation.

    Directory of Open Access Journals (Sweden)

    Young-Jin Park

    Full Text Available Flammulina velutipes is a fungus with health and medicinal benefits that has been used for consumption and cultivation in East Asia. F. velutipes is also known to degrade lignocellulose and produce ethanol. The overlapping interests of mushroom production and wood bioconversion make F. velutipes an attractive new model for fungal wood related studies. Here, we present the complete sequence of the F. velutipes genome. This is the first sequenced genome for a commercially produced edible mushroom that also degrades wood. The 35.6-Mb genome contained 12,218 predicted protein-encoding genes and 287 tRNA genes assembled into 11 scaffolds corresponding with the 11 chromosomes of strain KACC42780. The 88.4-kb mitochondrial genome contained 35 genes. Well-developed wood degrading machinery with strong potential for lignin degradation (69 auxiliary activities, formerly FOLymes and carbohydrate degradation (392 CAZymes, along with 58 alcohol dehydrogenase genes were highly expressed in the mycelium, demonstrating the potential application of this organism to bioethanol production. Thus, the newly uncovered wood degrading capacity and sequential nature of this process in F. velutipes, offer interesting possibilities for more detailed studies on either lignin or (hemi- cellulose degradation in complex wood substrates. The mutual interest in wood degradation by the mushroom industry and (ligno-cellulose biomass related industries further increase the significance of F. velutipes as a new model.

  13. Whole genome and global gene expression analyses of the model mushroom Flammulina velutipes reveal a high capacity for lignocellulose degradation.

    Science.gov (United States)

    Park, Young-Jin; Baek, Jeong Hun; Lee, Seonwook; Kim, Changhoon; Rhee, Hwanseok; Kim, Hyungtae; Seo, Jeong-Sun; Park, Hae-Ran; Yoon, Dae-Eun; Nam, Jae-Young; Kim, Hong-Il; Kim, Jong-Guk; Yoon, Hyeokjun; Kang, Hee-Wan; Cho, Jae-Yong; Song, Eun-Sung; Sung, Gi-Ho; Yoo, Young-Bok; Lee, Chang-Soo; Lee, Byoung-Moo; Kong, Won-Sik

    2014-01-01

    Flammulina velutipes is a fungus with health and medicinal benefits that has been used for consumption and cultivation in East Asia. F. velutipes is also known to degrade lignocellulose and produce ethanol. The overlapping interests of mushroom production and wood bioconversion make F. velutipes an attractive new model for fungal wood related studies. Here, we present the complete sequence of the F. velutipes genome. This is the first sequenced genome for a commercially produced edible mushroom that also degrades wood. The 35.6-Mb genome contained 12,218 predicted protein-encoding genes and 287 tRNA genes assembled into 11 scaffolds corresponding with the 11 chromosomes of strain KACC42780. The 88.4-kb mitochondrial genome contained 35 genes. Well-developed wood degrading machinery with strong potential for lignin degradation (69 auxiliary activities, formerly FOLymes) and carbohydrate degradation (392 CAZymes), along with 58 alcohol dehydrogenase genes were highly expressed in the mycelium, demonstrating the potential application of this organism to bioethanol production. Thus, the newly uncovered wood degrading capacity and sequential nature of this process in F. velutipes, offer interesting possibilities for more detailed studies on either lignin or (hemi-) cellulose degradation in complex wood substrates. The mutual interest in wood degradation by the mushroom industry and (ligno-)cellulose biomass related industries further increase the significance of F. velutipes as a new model.

  14. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    Science.gov (United States)

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted ...

  15. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

    NARCIS (Netherlands)

    Wain, Louise V.; Shrine, Nick R. G.; Artigas, Maria Soler; Erzurumluoglu, A Mesut; Noyvert, Boris; Bossini-Castillo, Lara; Obeidat, Ma'en; Henrys, Amanda P.; Portelli, Michael A.; Hall, Robert J; Billington, Charlotte K.; Rimington, Tracy L; Fenech, Anthony G; John, Catherine; Blake, Tineka; Jackson, Victoria E.; Allen, Richard J; Prins, Bram P.; Campbell, Archie; Porteous, David J.; Jarvelin, Marjo-Riitta; Wielscher, Matthias; Jamess, Alan L.; Hui, Jennie; Wareham, Nicholas J.; Zhao, Jing Hua; Wilson, James F.; Joshi, Peter K.; Stubbe, Beate; Rawal, Rajesh; Schulz, Holger; Imboden, Medea; Probst-Hensch, Nicole M.; Karrasch, Stefan; Gieger, Christian; Deary, Ian J.; Harris, Sarah E.; Marten, Jonathan; Rudan, Igor; Enroth, Stefan; Gyllensten, Ulf; Kerr, Shona M.; Polasek, Ozren; Kahonen, Mika; Surakka, Ida; Vitart, Veronique; Hayward, Caroline; Lehtimaki, Terho; Raitakari, Olli T.; Evans, David M.; Henderson, A. John; Pennell, Craig E.; Wang, Carol A.; Sly, Peter D.; Wan, Emily S; Busch, Robert; Hobbs, Brian D; Litonjua, Augusto; Sparrow, David W; Gulsvik, Amund; Bakke, Per S.; Crapo, James D.; Beaty, Terri H.; Hansel, Nadia N.; Mathias, Rasika A.; Ruczinski, Ingo; Barnes, Kathleen C.; Bosse, Yohan; Joubert, Philippe; van den Berge, Maarten; Brandsma, Corry-Anke; Pare, Peter D.; Sin, Don; Nickle, David C.; Hao, Ke; Gottesman, Omri; Dewey, Frederick E; Bruse, Shannon E; Carey, David J.; Kirchner, H Lester; Jonsson, Stefan; Thorleifsson, Gudmar; Jonsdottir, Ingileif; Gislason, Thorarinn; Stefansson, Kari; Schurmann, Claudia; Nadkarni, Girish N; Bottinger, Erwin P.; Loos, Ruth J. F.; Walters, Robin G.; Chen, Zhengming; Millwood, Iona Y; Vaucher, Julien; Kurmi, Om P; Li, Liming; Hansell, Anna L.; Brightling, Chris; Zeggini, Eleftheria; Cho, Michael H.; Silverman, Edwin K.; Sayers, Ian; Trynka, Gosia; Morris, Andrew P.; Strachan, David P.; Halls, Ian P.; Tobin, Martin D.

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 in

  16. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    2016-01-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 ca

  17. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

    NARCIS (Netherlands)

    Wain, Louise V; Shrine, Nick; Artigas, María Soler; Erzurumluoglu, A Mesut; Noyvert, Boris; Bossini-Castillo, Lara; Obeidat, Ma'en; Henry, Amanda P; Portelli, Michael A; Hall, Robert J; Billington, Charlotte K; Rimington, Tracy L; Fenech, Anthony G; John, Catherine; Blake, Tineka; Jackson, Victoria E; Allen, Richard J; Prins, Bram P; Campbell, Archie; Porteous, David J; Jarvelin, Marjo-Riitta; Wielscher, Matthias; James, Alan L; Hui, Jennie; Wareham, Nicholas J; Zhao, Jing Hua; Wilson, James F; Joshi, Peter K; Stubbe, Beate; Rawal, Rajesh; Schulz, Holger; Imboden, Medea; Probst-Hensch, Nicole M; Karrasch, Stefan; Gieger, Christian; Deary, Ian J; Harris, Sarah E; Marten, Jonathan; Rudan, Igor; Enroth, Stefan; Gyllensten, Ulf; Kerr, Shona M; Polasek, Ozren; Kähönen, Mika; Surakka, Ida; Vitart, Veronique; Hayward, Caroline; Lehtimäki, Terho; Raitakari, Olli T; Evans, David M; Henderson, A John; Pennell, Craig E; Wang, Carol A; Sly, Peter D; Wan, Emily S; Busch, Robert; Hobbs, Brian D; Litonjua, Augusto A; Sparrow, David W; Gulsvik, Amund; Bakke, Per S; Crapo, James D; Beaty, Terri H; Hansel, Nadia N; Mathias, Rasika A; Ruczinski, Ingo; Barnes, Kathleen C; Bossé, Yohan; Joubert, Philippe; van den Berge, Maarten; Brandsma, Corry-Anke; Paré, Peter D; Sin, Don D; Nickle, David C; Hao, Ke; Gottesman, Omri; Dewey, Frederick E; Bruse, Shannon E; Carey, David J; Kirchner, H Lester; Jonsson, Stefan; Thorleifsson, Gudmar; Jonsdottir, Ingileif; Gislason, Thorarinn; Stefansson, Kari; Schurmann, Claudia; Nadkarni, Girish; Bottinger, Erwin P; Loos, Ruth J F; Walters, Robin G; Chen, Zhengming; Millwood, Iona Y; Vaucher, Julien; Kurmi, Om P; Li, Liming; Hansell, Anna L; Brightling, Chris; Zeggini, Eleftheria; Cho, Michael H; Silverman, Edwin K; Sayers, Ian; Trynka, Gosia; Morris, Andrew P; Strachan, David P; Hall, Ian P; Tobin, Martin D

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 in

  18. Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Deng, Min; Wei, Ling; Zuo, Xianbo; Tian, Yanghua; Xie, Fei; Hu, Panpan; Zhu, Chunyan; Yu, Fengqiong; Meng, Yu; Wang, Honghao; Zhang, Fangfang; Ma, Huijuan; Ye, Rong; Cheng, Huaidong; Du, Jing; Dong, Wenwen; Zhou, Shanshan; Wang, Changqing; Wang, Yu; Wang, Jingye; Chen, Xianwen; Sun, Zhongwu; Zhou, Nong; Jiang, Yubao; Liu, Xiuxiu; Li, Xiaogang; Zhang, Nan; Liu, Na; Guan, Yingjun; Han, Yongsheng; Han, Yongzhu; Lv, Xinyi; Fu, Yu; Yu, Hui; Xi, Chunhua; Xie, Dandan; Zhao, Qiyuan; Xie, Peng; Wang, Xin; Zhang, Zhijun; Shen, Lu; Cui, Yong; Yin, Xianyong; Cheng, Hui; Liang, Bo; Zheng, Xiaodong; Lee, Tatia M. C.; Chen, Gang; Zhou, Fusheng; Veldink, Hendrik; Robberecht, Wim; Landers, John E.; Andersen, Peter M.; Al-Chalabi, Ammar; Shaw, Chris; Liu, Chunfeng; Tang, Beisha; Xiao, Shangxi; Robertson, Janice; Zhang, Fengyu; van den Berg, Leonard H.; Sun, Liangdan; Liu, Jianjun; Yang, Sen; Ju, Xiaodong; Wang, Kai; Zhang, Xuejun

    2013-01-01

    To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were ana

  19. Characterization and Comparative Genomic Analyses of Pseudomonas aeruginosa Phage PaoP5: New Members Assigned to PAK_P1-like Viruses

    Science.gov (United States)

    Shen, Mengyu; Le, Shuai; Jin, Xiaolin; Li, Gang; Tan, Yinling; Li, Ming; Zhao, Xia; Shen, Wei; Yang, Yuhui; Wang, Jing; Zhu, Hongbin; Li, Shu; Rao, Xiancai; Hu, Fuquan; Lu, Shuguang

    2016-01-01

    As a potential alternative to antibiotics, phages can be used to treat multi-drug resistant bacteria. As such, the biological characteristics of p