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Sample records for candidate genes putatively

  1. A putative greigite-type magnetosome gene cluster from the candidate phylum Latescibacteria.

    Science.gov (United States)

    Lin, Wei; Pan, Yongxin

    2015-04-01

    The intracellular biomineralization of magnetite and/or greigite magnetosomes in magnetotactic bacteria (MTB) is strictly controlled by a group of conserved genes, termed magnetosome genes, which are organized as clusters (or islands) in MTB genomes. So far, all reported MTB are affiliated within the Proteobacteria phylum, the Nitrospirae phylum and the candidate division OP3. Here, we report the discovery of a putative magnetosome gene cluster structure from the draft genome of an uncultivated bacterium belonging to the candidate phylum Latescibacteria (formerly candidate division WS3) recently recovered by Rinke and colleagues, which contains 10 genes with homology to magnetosome mam genes of magnetotactic Proteobacteria and Nitrospirae. Moreover, these genes are phylogenetically closely related to greigite-type magnetosome genes that were only found from the Deltaproteobacteria MTB before, suggesting that the greigite genes may originate earlier than previously imagined. These findings indicate that some members of Latescibacteria may be capable of forming greigite magnetosomes, and thus may play previously unrecognized roles in environmental iron and sulfur cycles. The conserved genomic structure of magnetosome gene cluster in Latescibacteria phylum supports the hypothesis of horizontal transfer of these genes among distantly related bacterial groups in nature. PMID:25382584

  2. Saturation mapping of QTL regions and identification of putative candidate genes for drought tolerance in rice.

    Science.gov (United States)

    Nguyen, T T T; Klueva, N; Chamareck, V; Aarti, A; Magpantay, G; Millena, A C M; Pathan, M S; Nguyen, H T

    2004-08-01

    We have developed 85 new markers (50 RFLPs, 5 SSRs, 12 DD cDNAs, 9 ESTs, 8 HSP-encoding cDNAs and one BSA-derived AFLP marker) for saturation mapping of QTL regions for drought tolerance in rice, in our efforts to identify putative candidate genes. Thirteen of the markers were localized in the close vicinity of the targeted QTL regions. Fifteen of the additional markers mapped, respectively, inside one QTL region controlling osmotic adjustment on chromosome 3 ( oa3.1) and 14 regions that affect root traits on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10 and 12. Differential display was used to identify more putative candidate genes and to saturate the QTL regions of the genetic map. Eleven of the isolated cDNA clones were found to be derived from drought-inducible genes. Two of them were unique and did not match any genes in the GenBank, while nine were highly similar to cDNAs encoding known proteins, including a DnaJ-related protein, a zinc-finger protein, a protease inhibitor, a glutathione-S-transferase, a DNA recombinase, and a protease. Twelve new cDNA fragments were mapped onto the genetic linkage map; seven of these mapped inside, or in close proximity to, the targeted QTL regions determining root thickness and osmotic adjustment capacity. The gene I12A1, which codes for a UDP-glucose 4-epimerase homolog, was identified as a putative target gene within the prt7.1/brt7.1 QTL region, as it is involved in the cell wall biogenesis pathway and hence may be implicated in modulating the ability of rice roots to penetrate further into the substratum when exposed to drought conditions. RNAs encoding elongation factor 1beta, a DnaJ-related protein, and a homolog of wheat zinc-finger protein were more prominently induced in the leaves of IR62266 (the lowland rice parent of the mapping materials used) than in those of CT9993 (the upland rice parent) under drought conditions. Homologs of 18S ribosomal RNA, and mRNAs for a multiple-stress induced zinc-finger protein, a protease

  3. Validation of candidate genes putatively associated with resistance to SCMV and MDMV in maize (Zea mays L. by expression profiling

    Directory of Open Access Journals (Sweden)

    Wenzel Gerhard

    2009-02-01

    Full Text Available Abstract Background The potyviruses sugarcane mosaic virus (SCMV and maize dwarf mosaic virus (MDMV are major pathogens of maize worldwide. Two loci, Scmv1 and Scmv2, have ealier been shown to confer complete resistance to SCMV. Custom-made microarrays containing previously identified SCMV resistance candidate genes and resistance gene analogs were utilised to investigate and validate gene expression and expression patterns of isogenic lines under pathogen infection in order to obtain information about the molecular mechanisms involved in maize-potyvirus interactions. Results By employing time course microarray experiments we identified 68 significantly differentially expressed sequences within the different time points. The majority of differentially expressed genes differed between the near-isogenic line carrying Scmv1 resistance locus at chromosome 6 and the other isogenic lines. Most differentially expressed genes in the SCMV experiment (75% were identified one hour after virus inoculation, and about one quarter at multiple time points. Furthermore, most of the identified mapped genes were localised outside the Scmv QTL regions. Annotation revealed differential expression of promising pathogenesis-related candidate genes, validated by qRT-PCR, coding for metallothionein-like protein, S-adenosylmethionine synthetase, germin-like protein or 26S ribosomal RNA. Conclusion Our study identified putative candidate genes and gene expression patterns related to resistance to SCMV. Moreover, our findings support the effectiveness and reliability of the combination of different expression profiling approaches for the identification and validation of candidate genes. Genes identified in this study represent possible future targets for manipulation of SCMV resistance in maize.

  4. Comparative genomics analysis of Mycobacterium ulcerans for the identification of putative essential genes and therapeutic candidates.

    Directory of Open Access Journals (Sweden)

    Azeem Mehmood Butt

    Full Text Available Mycobacterium ulcerans, the causative agent of Buruli ulcer, is the third most common mycobacterial disease after tuberculosis and leprosy. The present treatment options are limited and emergence of treatment resistant isolates represents a serious concern and a need for better therapeutics. Conventional drug discovery methods are time consuming and labor-intensive. Unfortunately, the slow growing nature of M. ulcerans in experimental conditions is also a barrier for drug discovery and development. In contrast, recent advancements in complete genome sequencing, in combination with cheminformatics and computational biology, represent an attractive alternative approach for the identification of therapeutic candidates worthy of experimental research. A computational, comparative genomics workflow was defined for the identification of novel therapeutic candidates against M. ulcerans, with the aim that a selected target should be essential to the pathogen, and have no homology in the human host. Initially, a total of 424 genes were predicted as essential from the M. ulcerans genome, via homology searching of essential genome content from 20 different bacteria. Metabolic pathway analysis showed that the most essential genes are associated with carbohydrate and amino acid metabolism. Among these, 236 proteins were identified as non-host and essential, and could serve as potential drug and vaccine candidates. Several drug target prioritization parameters including druggability were also calculated. Enzymes from several pathways are discussed as potential drug targets, including those from cell wall synthesis, thiamine biosynthesis, protein biosynthesis, and histidine biosynthesis. It is expected that our data will facilitate selection of M. ulcerans proteins for successful entry into drug design pipelines.

  5. A cohort of balanced reciprocal translocations associated with dyslexia: identification of two putative candidate genes at DYX1

    DEFF Research Database (Denmark)

    Buonincontri, Roberta; Bache, Iben; Silahtaroglu, Asli;

    2011-01-01

    Dyslexia is one of the most common neurodevelopmental disorders where likely many genes are involved in the pathogenesis. So far six candidate dyslexia genes have been proposed, and two of these were identified by rare chromosomal translocations in affected individuals. By systematic re......-examination of all translocation carriers in Denmark, we have identified 16 different translocations associated with dyslexia. In four families, where the translocation co-segregated with the phenotype, one of the breakpoints concurred (at the cytogenetic level) with either a known dyslexia linkage region--at 15q21...... (DYX1), 2p13 (DYX3) and 1p36 (DYX8)--or an unpublished linkage region at 19q13. As a first exploitation of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial translocation with the 15q21 breakpoint....

  6. Validation of candidate genes putatively associated with resistance to SCMV and MDMV in maize (Zea mays L.) by expression profiling

    DEFF Research Database (Denmark)

    Uzarowska, Anna; Dionisio, Giuseppe; Sarholz, Barbara;

    2009-01-01

    Background The potyviruses sugarcane mosaic virus (SCMV) and maize dwarf mosaic virus (MDMV) are major pathogens of maize worldwide. Two loci, Scmv1 and Scmv2, have ealier been shown to confer complete resistance to SCMV. Custom-made microarrays containing previously identified SCMV resistance...... candidate genes and resistance gene analogs were utilised to investigate and validate gene expression and expression patterns of isogenic lines under pathogen infection in order to obtain information about the molecular mechanisms involved in maize-potyvirus interactions. Results By employing time course...... expressed genes in the SCMV experiment (75%) were identified one hour after virus inoculation, and about one quarter at multiple time points. Furthermore, most of the identified mapped genes were localised outside the Scmv QTL regions. Annotation revealed differential expression of promising pathogenesis...

  7. Identification of putative candidate genes for red rot resistance in sugarcane (Saccharum species hybrid) using LD-based association mapping.

    Science.gov (United States)

    Singh, Ram K; Banerjee, Nandita; Khan, M S; Yadav, Sonia; Kumar, Sanjeev; Duttamajumder, S K; Lal, Ram Ji; Patel, Jinesh D; Guo, H; Zhang, Dong; Paterson, Andrew H

    2016-06-01

    Red rot is a serious disease of sugarcane caused by the fungus Colletotrichum falcatum that has a colossal damage potential. The fungus, prevalent mainly in the Indian sub-continent, keeps on producing new pathogenic strains leading to breakdown of resistance in newly released varieties and hence the deployment of linked markers for marker-assisted selection for resistance to this disease can fine tune the breeding programme. This study based on a panel of 119 sugarcane genotypes fingerprinted for 944 SSR alleles was undertaken with an aim to identify marker-trait associations (MTAs) for resistance to red rot. Mixed linear model containing population structure and kinship as co-factor detected four MTAs that were able to explain 10-16 % of the trait variation, individually. Among the four MTAs, EST sequences diagnostic of three could be BLAST searched to the sorghum genome with significant sequence homology. Several genes encoding important plant defence related proteins, viz., cytochrome P450, Glycerol-3-phosphate transporter-1, MAP Kinase-4, Serine/threonine-protein kinase, Ring finger domain protein and others were localized to the vicinity of these MTAs. These positional candidate genes are worth of further investigation and possibly these could contribute directly to red rot resistance, and may find a potential application in marker-assisted sugarcane breeding. PMID:26961118

  8. ZDHHC8 as a candidate gene for schizophrenia: Analysis of a putative functional intronic marker in case-control and family-based association studies

    Directory of Open Access Journals (Sweden)

    Jabs Burkhard

    2005-10-01

    Full Text Available Abstract Background The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. Methods Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186. Results In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity χ2 = 4.43; p = 0.035. The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. Conclusion The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.

  9. Candidate gene prioritization with Endeavour.

    Science.gov (United States)

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/. PMID:27131783

  10. Candidate genes detected in transcriptome studies are strongly dependent on genetic background.

    Directory of Open Access Journals (Sweden)

    Pernille Sarup

    Full Text Available Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds.

  11. DNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes

    OpenAIRE

    Liang, Fang Ting; Nelson, F. Kenneth; Fikrig, Erol

    2002-01-01

    A DNA microarray containing fragments of 137 Borrelia burgdorferi B31 putative lipoprotein genes was used to examine Lyme disease spirochetes. DNA from B. burgdorferi sensu stricto B31, 297, and N40; Borrelia garinii IP90; and Borrelia afzelii P/Gau was fluorescently labeled and hybridized to the microarray, demonstrating the degree to which the individual putative lipoprotein genes were conserved among the genospecies. These data show that a DNA microarray can globally examine the genes enco...

  12. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus.

    Directory of Open Access Journals (Sweden)

    Kwang-Hwan Kim

    Full Text Available An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL for resistance to powdery mildew (PMR, seed size (SS, and fruit shape (FS were analyzed. The map consists of 14 linkage groups (LGs defined by 174 cleaved amplified polymorphic sequences (CAPS, 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02, explained 80.0% of the phenotypic variation (LOD = 30.76. This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM and wsb2-39 (13.97 cM. The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78. The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37 and was flanked by two CAPS, wsb3-24 (1.91 cM and wsb3-9 (7.00 cM. Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

  13. Bioinformatics methods for identifying candidate disease genes

    NARCIS (Netherlands)

    Driel, M.A. van; Brunner, H.G.

    2006-01-01

    With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes. Combining positional information with disease characteristics and functional information i

  14. Cattle Candidate Genes for Milk Production Traits

    OpenAIRE

    Kadlec, Tomáš

    2012-01-01

    The aim of this thesis is to make an overview of important candidate genes affecting milk yield and milk quality parameters, with an emphasis on genes associated with the quantity and quality of milk proteins and milk fat.

  15. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137

    Science.gov (United States)

    Devanna, Paolo; Vernes, Sonja C.

    2014-02-01

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.

  16. Evaluating historical candidate genes for schizophrenia

    DEFF Research Database (Denmark)

    Farrell, M S; Werge, T; Sklar, P;

    2015-01-01

    Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24...... of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published...... on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why...

  17. Candidate genes for behavioural ecology

    NARCIS (Netherlands)

    Fitzpatrick, M.J.; Ben-Sahar, Y.; Smid, H.M.; Vet, L.E.M.; Robinson, G.E.; Sokolowski, M.B.

    2005-01-01

    In spite of millions of years of evolutionary divergence, the conservation of gene function is common across distant lineages. As such, genes that are known to influence behaviour in one organism are likely to influence similar behaviours in other organisms. Recent studies of the evolution of behavi

  18. Alcoholism and Alternative Splicing of Candidate Genes

    OpenAIRE

    Toshikazu Sasabe; Shoichi Ishiura

    2010-01-01

    Gene expression studies have shown that expression patterns of several genes have changed during the development of alcoholism. Gene expression is regulated not only at the level of transcription but also through alternative splicing of pre-mRNA. In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor) may form the basis of the mechanisms underlying the pathophysiology of alcoholism. These reports sugg...

  19. Candidate genes in ocular dominance plasticity

    Directory of Open Access Journals (Sweden)

    M. Liset Rietman

    2012-02-01

    Full Text Available The objective of this study was to identify new candidate genes involved in experience-dependent plasticity. To this aim, we combined previously obtained data from recombinant inbred BXD strains on ocular dominance (OD plasticity and gene expression levels in the neocortex. We validated our approach using a list of genes which alter OD plasticity when inactivated. The expression levels of one fifth of these genes correlated with the amount of OD plasticity. Moreover, the two genes with the highest relative inter-strain differences were among the correlated genes. This suggests that correlation between gene expression levels and OD plasticity is indeed likely to point to genes with a causal role in modulating or generating plasticity in the visual cortex. After this validation on known plasticity genes, we identified new candidate genes by a multi-step approach. First, a list was compiled of all genes of which the expression level in BXD strains correlate with the amount of OD plasticity. To narrow this list to the more promising candidates, we took its cross-section with a list of genes co-regulated with the sensitive period for OD plasticity and a list of genes associated with pathways implicated in OD plasticity. This analysis resulted in a list of 32 candidate genes. The list contained unproven, but not surprising, candidates, such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of the GABA(A receptor, acetylcholine esterase and the catalytic subunit of cAMP-dependent protein kinase A. This was indicative of the viability of our approach, but more interesting were the novel candidate genes: Akap7, Akt1, Camk2d, Cckbr, Cd44, Crim1, Ctdsp2, Dnajc5, Gnai1, Itpka, Mapk8, Nbea, Nfatc3, Nlk, Npy5r, Phf21a, Phip, Ppm1l, Ppp1r1b, Rbbp4, Slc1a3, Slit2, Socs2, Spock3, St8sia1, Zfp207. The possible role of some of these candidates is discussed in the article.

  20. Candidate genes in ocular dominance plasticity

    NARCIS (Netherlands)

    M.L. Rietman; J.-P. Sommeijer; C.N. Levelt; J.A. Heimel; A.B. Brussaard; J.G.G. Borst; Y. Elgersma; N. Galjart; G.T. van der Horst; C.M. Pennartz; A.B. Smit; B.M. Spruijt; M. Verhage; C.I. de Zeeuw

    2012-01-01

    Many studies have been devoted to the identification of genes involved in experience-dependent plasticity in the visual cortex. To discover new candidate genes, we have reexamined data from one such study on ocular dominance (OD) plasticity in recombinant inbred BXD mouse strains. We have correlated

  1. Cattle Candidate Genes for Meat Production Traits

    OpenAIRE

    Bláhová, Alice

    2013-01-01

    The objective of this study was to compile a summary of the most important candidate genes for meat production. The studied genes were: GH, GHR, MSTN, MyoD family, leptin, IGF, TG5, SCD, DGAT and STAT5A. Growth hormone (GH) is involved in physiological processes of growth and metabolism. Growth hormone receptor (GHR) has been proposed as a candidate gene for meat production in cattle. Myostatin is a significant marker. It affects the amount of muscle, reduces marbling and elevate meat tendern...

  2. Candidate chemosensory genes in the Stemborer Sesamia nonagrioides.

    Science.gov (United States)

    Glaser, Nicolas; Gallot, Aurore; Legeai, Fabrice; Montagné, Nicolas; Poivet, Erwan; Harry, Myriam; Calatayud, Paul-André; Jacquin-Joly, Emmanuelle

    2013-01-01

    The stemborer Sesamia nonagrioides is an important pest of maize in the Mediterranean Basin. Like other moths, this noctuid uses its chemosensory system to efficiently interact with its environment. However, very little is known on the molecular mechanisms that underlie chemosensation in this species. Here, we used next-generation sequencing (454 and Illumina) on different tissues from adult and larvae, including chemosensory organs and female ovipositors, to describe the chemosensory transcriptome of S. nonagrioides and identify key molecular components of the pheromone production and detection systems. We identified a total of 68 candidate chemosensory genes in this species, including 31 candidate binding-proteins and 23 chemosensory receptors. In particular, we retrieved the three co-receptors Orco, IR25a and IR8a necessary for chemosensory receptor functioning. Focusing on the pheromonal communication system, we identified a new pheromone-binding protein in this species, four candidate pheromone receptors and 12 carboxylesterases as candidate acetate degrading enzymes. In addition, we identified enzymes putatively involved in S. nonagrioides pheromone biosynthesis, including a ∆11-desaturase and different acetyltransferases and reductases. RNAseq analyses and RT-PCR were combined to profile gene expression in different tissues. This study constitutes the first large scale description of chemosensory genes in S. nonagrioides. PMID:23781142

  3. Putative Genes Involved in Saikosaponin Biosynthesis in Bupleurum Species

    OpenAIRE

    Shu-Jiau Chiou; Tsai-Yun Lin; Chung-Yi Chiou

    2013-01-01

    Alternative medicinal agents, such as the herb Bupleurum, are increasingly used in modern medicine to supplement synthetic drugs. First, we present a review of the currently known effects of triterpene saponins-saikosaponins of Bupleurum species. The putative biosynthetic pathway of saikosaponins in Bupleurum species is summarized, followed by discussions on identification and characterization of genes involved in the biosynthesis of saikosaponins. The purpose is to provide a brief review of ...

  4. Searching for candidate genes for male infertility

    Institute of Scientific and Technical Information of China (English)

    B.N.Truong; E.K.Moses; J.E.Armes; D.J.Venter; H.W.G.Baker

    2003-01-01

    Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression,known mutations and single nucleotide polymorphisms (SNPs). Methods and Results: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. Conclusion: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome. ( Asian J Andro1 2003 Jun; 5:137-147 )

  5. Putative Genes Involved in Saikosaponin Biosynthesis in Bupleurum Species

    Directory of Open Access Journals (Sweden)

    Shu-Jiau Chiou

    2013-06-01

    Full Text Available Alternative medicinal agents, such as the herb Bupleurum, are increasingly used in modern medicine to supplement synthetic drugs. First, we present a review of the currently known effects of triterpene saponins-saikosaponins of Bupleurum species. The putative biosynthetic pathway of saikosaponins in Bupleurum species is summarized, followed by discussions on identification and characterization of genes involved in the biosynthesis of saikosaponins. The purpose is to provide a brief review of gene extraction, functional characterization of isolated genes and assessment of expression patterns of genes encoding enzymes in the process of saikosaponin production in Bupleurum species, mainly B. kaoi. We focus on the effects of MeJA on saikosaponin production, transcription patterns of genes involved in biosynthesis and on functional depiction.

  6. Candidate genes for drought tolerance and improved productivity in rice (Oryza sativa L.)

    Indian Academy of Sciences (India)

    M S Vinod; Naveen Sharma; K Manjunatha; Adnan Kanbar; N B Prakash; H E Shashidhar

    2006-03-01

    Candidate genes are sequenced genes of known biological action involved in the development or physiology of a trait. Twenty-one putative candidate genes were designed after an exhaustive search in the public databases along with an elaborate literature survey for candidate gene products and/or regulatory sequences associated with enhanced drought resistance. The downloaded sequences were then used to design primers considering the flanking sequences as well. Polymerase chain reaction (PCR) performed on 10 diverse cultivars that involved Japonica, Indica and local accessions, revealed 12 polymorphic candidate genes. Seven polymorphic candidate genes were then utilized to genotype 148 individuals of CT9993 × IR62266 doubled haploid (DH) mapping population. The segregation data were tested for deviation from the expected Mendelian ratio (1:1) using a Chi-square test (<1%). Based on this, four candidate genes were assessed to be significant and the remaining three, as non-significant. All the significant candidate genes were biased towards CT9993, the female parent in the DH mapping population. Single-marker analysis strongly associated ( < 1%) them to different traits under both well-watered and low-moisture stress conditions. Two candidate genes, EXP15 and EXP13, were found to be associated with root number and silicon content in the stem respectively, under both well-watered and low-moisture stress conditions.

  7. Candidate gene effects on beef quality

    OpenAIRE

    Ekerljung, Marie

    2012-01-01

    The contribution of five candidate genes to the variation in meat tenderness, pH, colour, marbling and water holding capacity (WHC) was analysed in muscle samples from 243 young bulls of Angus, Charolais, Hereford, Limousin, or Simmental breed, raised in Swedish commercial herds. The animals were genotyped for single nucleotide polymorphisms (SNPs) in the genes encoding calpain 1 (CAPN1:c.947G>C), calpastatin, (CAST:c.155C>T), diacylglycerol O-acyltransferase 1 (DGAT1), leptin (UASMS2C>T) a...

  8. Immunological characterization of recombinantWuchereria bancrofti cuticular collagen (COL-4) as putative vaccine candidate for human lymphatic filariasis

    Institute of Scientific and Technical Information of China (English)

    Chakkaravarthy Arunkumar; Pandurangan Pandiaraja; P. R. Prince; Perumal Kaliraj

    2014-01-01

    Objective:To elucidate immunoprophylactic potential of recombinantWuchereria bancrofti(W. bancrofti) cuticular collagen(COL-4) inBALB/c mice and filarial clinical samples.Methods:col-4 gene wasPCR amplified fromW. bancroftiL3 cDNA library and cloned in pRSETB vector. RecombinantCOL-4 was over expressed in salt inducible system and was purified by nickel affinity chromatography.Humoral and cellular responses were measured byELISA and peripheral blood mononuclear cells(PBMC) of various filarial clinical samples respectively using purified recombinantCOL-4 antigen.Then the protective immune responses ofCOL-4 immunizedBALB/c mice were characterized.Results:Sequence analysis ofCOL-4 with human host proteins reveals lack of homology.The recombinantCOL-4 was found to be at15 kDa fusion protein.The affinity purifiedCOL-4 showed significant reactivity with putatively immune sera and in a similar fashion it demonstrated marked proliferation inPBMC samples.Immunization studies in experimental filarial host(mice) elicited significant titers with protective antibody isotype profile(IgM and IgG).Cellular immune responses were also significant in terms of splenocytes proliferation assay on mice samples.Conclusions:Our immunological findings in experimental host suggestTh2 mediated immune response.Hence, we propose thatW. bancroftiCOL-4 could be an efficacious vaccine candidate against lymphatic filariasis.

  9. Identification and characterization of putative CIPK genes in maize

    Institute of Scientific and Technical Information of China (English)

    Xifeng Chen; Zhimin Gu; Dedong Xin; Liang Hao; Chengjie Liu; Ji Huang; Bojun Ma; Hongsheng Zhang

    2011-01-01

    Calcium (Ca) plays a crucial role as a second messenger in intracellular signaling elicited by developmental and environmental cues.Calcineurin B-like proteins (CBLs) and their target proteins, CBL-interacting protein kinases (CIPKs) have emerged as a key Ca2 +-mediated signaling network in response to stresses in plants. Bioinformatic analysis was used to identify 43 putative ZmCIPK (Zea mays CIPK) genes in the genome of maize inbred line B73. Based on gene structures, these ZmCIPKs were divided into intron-rich and intron-poor groups.Phylogenetic analysis indicated that the ZmCIPK family had a high evolutionary relationship with the rice CIPK family of 30 members.Microarray data and RT-PCR assay showed that ZmCIPK genes transcriptionally responded to abiotic stresses, and that 24, 31, 20 and 19ZmCIPK genes were up-regulated by salt, drought, heat and cold stresses, respectively. There were different expression patterns of ZmCIPKs between cold-tolerant inbred line B73 and cold-sensitive inbred line Mol7 under cold stress. Our findings will aid further molecular dissection of biological functions of the CIPKs in maize, and provide new insight into the CBL-CIPK signaling network in plants.

  10. Discovery of putative capsaicin biosynthetic genes by RNA-Seq and digital gene expression analysis of pepper

    Science.gov (United States)

    Zhang, Zi-Xin; Zhao, Shu-Niu; Liu, Gao-Feng; Huang, Zu-Mei; Cao, Zhen-Mu; Cheng, Shan-Han; Lin, Shi-Sen

    2016-01-01

    The Indian pepper ‘Guijiangwang’ (Capsicum frutescens L.), one of the world’s hottest chili peppers, is rich in capsaicinoids. The accumulation of the alkaloid capsaicin and its analogs in the epidermal cells of the placenta contribute to the pungency of Capsicum fruits. To identify putative genes involved in capsaicin biosynthesis, RNA-Seq was used to analyze the pepper’s expression profiles over five developmental stages. Five cDNA libraries were constructed from the total RNA of placental tissue and sequenced using an Illumina HiSeq 2000. More than 19 million clean reads were obtained from each library, and greater than 50% of the reads were assignable to reference genes. Digital gene expression (DGE) profile analysis using Solexa sequencing was performed at five fruit developmental stages and resulted in the identification of 135 genes of known function; their expression patterns were compared to the capsaicin accumulation pattern. Ten genes of known function were identified as most likely to be involved in regulating capsaicin synthesis. Additionally, 20 new candidate genes were identified related to capsaicin synthesis. We use a combination of RNA-Seq and DGE analyses to contribute to the understanding of the biosynthetic regulatory mechanism(s) of secondary metabolites in a nonmodel plant and to identify candidate enzyme-encoding genes. PMID:27756914

  11. Expression and characterization of rice putative PAUSED gene

    Institute of Scientific and Technical Information of China (English)

    Chengguo Yao; Liangfa Ge; Wei Li; Botao Zhao; Chaoqun Li; Kangcheng Ruan; Hongxuan Lin; Youxin Jin

    2008-01-01

    In Arab idopsis, PA USED ( PSD ) encodes the ortholog of loslp/ exportin-t, which mediates the nuclear export of transfer RNA (tRNA) in yeast and mammals. However, in monocot plants such as rice, knowledge of the corresponding ortholog is limited, and its effects on growth development and productivity remain unknown. In this study, we verified a rice transfer-DNA insertional mutantpsd line and analyzed its phenotypes;the mutant displayed severe morphological defects including retarded development and low fertility compared with wild-type rice. Examining intronless tRNA-Tyr and intron-containing pre-tRNA-Ala expression levels in cytoplasmic and nuclear fraction with Northern blot analysis between wild -type and mutant leaf tissue suggested that rice PSD might be involved in tRNA export from the nucleus to the cytoplasm.Additionally, reverse transcription-polymerase chain reaction analysis revealed that PSD transcript was expressed throughout normal rice plant development, and subcellular localization assays showed that rice PSD protein was present in both the nucleus and cytoplasm. In summary, our data implied that the putative PSD gene might be indispensable for normal rice development and its function might be the same as that ofArabidopsis PSD.

  12. Isolation and characterization of 17 different genes encoding putative endopolygalacturonase genes from Rhizopus oryzae

    Science.gov (United States)

    Polygalacturonase enzymes are a valuable aid in the retting of flax for production of linens and, more recently, production of biofuels from citrus wastes. In a search of the recently sequenced Rhizopus oryzae strain 99-880 genome database, 18 putative endopolygalacturonase genes were identified, w...

  13. Identification of candidate genes for Fusarium yellows resistance in Chinese cabbage by differential expression analysis.

    Science.gov (United States)

    Shimizu, Motoki; Fujimoto, Ryo; Ying, Hua; Pu, Zi-jing; Ebe, Yusuke; Kawanabe, Takahiro; Saeki, Natsumi; Taylor, Jennifer M; Kaji, Makoto; Dennis, Elizabeth S; Okazaki, Keiichi

    2014-06-01

    Fusarium yellows caused by Fusarium oxysporum f. sp. conglutinans is an important disease of Brassica worldwide. To identify a resistance (R) gene against Fusarium yellows in Chinese cabbage (Brassica rapa var. pekinensis), we analyzed differential expression at the whole genome level between resistant and susceptible inbred lines using RNA sequencing. Four hundred and eighteen genes were significantly differentially expressed, and these were enriched for genes involved in response to stress or stimulus. Seven dominant DNA markers at putative R-genes were identified. Presence and absence of the sequence of the putative R-genes, Bra012688 and Bra012689, correlated with the resistance of six inbred lines and susceptibility of four inbred lines, respectively. In F(2) populations derived from crosses between resistant and susceptible inbred lines, presence of Bra012688 and Bra012689 cosegregated with resistance, suggesting that Bra012688 and Bra012689 are good candidates for fusarium yellows resistance in Chinese cabbage.

  14. Identification and characterization of a gene encoding a putative lysophosphatidyl acyltransferase from Arachis hypogaea

    Indian Academy of Sciences (India)

    Si-Long Chen; Jia-Quan Huang; Lei Yong; Yue-Ting Zhang; Xiao-Ping Ren; Yu-Ning Chen; Hui-Fang Jiang; Li-Ying Yan; Yu-Rong Li; Bo-Shou Liao

    2012-12-01

    Lysophosphatidyl acyltransferase (LPAT) is the important enzyme responsible for the acylation of lysophosphatidic acid (LPA), leading to the generation of phosphatidic acid (PA) in plant. Its encoding gene is an essential candidate for oil crops to improve oil composition and increase seed oil content through genetic engineering. In this study, a full-length AhLPAT4 gene was isolated via cDNA library screening and rapid amplification of cDNA ends (RACE); our data demonstrated that AhLPAT4 had 1631 nucleotides, encoding a putative 43.8 kDa protein with 383 amino acid residues. The deduced protein included a conserved acyltransferase domain and four motifs (I–IV) with putative LPA and acyl-CoA catalytic and binding sites. Bioinformatic analysis indicated that AhLPAT4 contained four transmembrane domains (TMDs), localized to the endoplasmic reticulum (ER) membrane; detailed analysis indicated that motif I and motifs II–III in AhLPAT4 were separated by the third TMD, which located on cytosolic and ER luminal side respectively, and hydrophobic residues on the surface of AhLPAT4 protein fold to form a hydrophobic tunnel to accommodate the acyl chain. Subcellular localization analysis confirmed that AhLPAT4 was a cytoplasm protein. Phylogenetic analysis revealed that AhLPAT4 had a high homology (63.7–78.3%) with putative LPAT4 proteins from Glycine max, Arabidopsis thaliana and Ricinus communis. AhLPAT4 was ubiquitously expressed in diverse tissues except in flower, which is almost undetectable. The expression analysis in different developmental stages in peanut seeds indicated that AhLPAT4 did not coincide with oil accumulation.

  15. Generating Genome-Scale Candidate Gene Lists for Pharmacogenomics

    DEFF Research Database (Denmark)

    Hansen, Niclas Tue; Brunak, Søren; Altman, R. B.

    2009-01-01

    , but they are expensive to generate manually and may therefore have incomplete coverage. We have developed a method that ranks 12,460 genes in the human genome on the basis of their potential relevance to a specific query drug and its putative indications. Our method uses known gene-drug interactions, networks of gene...

  16. High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2

    Directory of Open Access Journals (Sweden)

    Hellberg Michael E

    2010-05-01

    Full Text Available Abstract Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus, a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1 part of Oculina's innate immunity repertoire, and 2 evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.

  17. Isolation and sequencing of a putative promoter region of the murine G protein beta 1 subunit (GNB1) gene.

    Science.gov (United States)

    Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko; Wang, Xiao-Bing; Hembree, Cambria M; Goodman, Nancy L; Uhl, George R

    2002-02-01

    The expression of the heterotrimeric GTP-binding protein beta 1 subunit gene (GNB1) is regulated by psychostimulants such as cocaine and amphetamines. Since the up-regulation appears to be one of the candidate processes of sensitization, it is necessary to elucidate the cellular and molecular mechanism of the GNB1 gene regulation for a better understanding the establishment of sensitization. In the present study, we describe the isolation and nucleotide sequence analysis of the GNB1 gene promoter region. We have isolated approximately 10 kb of the 5'-flanking region of the mouse of GNB1 gene and found potential elements involved in putative transcriptional control of the GNB1, such as AP1, AP2, Sp1, cyclic AMP response element, and nuclear factor kappa B recognition sites, within the sequences 0.3 kb upstream from the putative transcription start site. This region was highly rich in G + C content, but lacked TATA or CATT boxes. Comparing the nucleotide sequence of the cDNA clone with the human genome databases using the BLAST program a region containing putative exon 1 and promoter of the human GNB1 gene in chromosome 1 was found. The cloning and sequence analysis of an extensive portion of the 5'-flanking regulatory region of the GNB1 gene provides new insights into the factors involved in the regulation by psychostimulants of GNB1 expression. PMID:12180136

  18. A transcription map of the 6p22.3 reading disability locus identifying candidate genes

    Directory of Open Access Journals (Sweden)

    Gruen Jeffrey R

    2003-06-01

    Full Text Available Abstract Background Reading disability (RD is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384 on chromosome 6p22.3, suggesting that a gene is located near this marker. Results In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. The identified genes were tested for their tissue specific expression by RT-PCR. Conclusions In total, five possible candidate genes for RD and other diseases mapping to this region were identified.

  19. Pathogenic Network Analysis Predicts Candidate Genes for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Yun-Xia Zhang

    2016-01-01

    Full Text Available Purpose. The objective of our study was to predicate candidate genes in cervical cancer (CC using a network-based strategy and to understand the pathogenic process of CC. Methods. A pathogenic network of CC was extracted based on known pathogenic genes (seed genes and differentially expressed genes (DEGs between CC and normal controls. Subsequently, cluster analysis was performed to identify the subnetworks in the pathogenic network using ClusterONE. Each gene in the pathogenic network was assigned a weight value, and then candidate genes were obtained based on the weight distribution. Eventually, pathway enrichment analysis for candidate genes was performed. Results. In this work, a total of 330 DEGs were identified between CC and normal controls. From the pathogenic network, 2 intensely connected clusters were extracted, and a total of 52 candidate genes were detected under the weight values greater than 0.10. Among these candidate genes, VIM had the highest weight value. Moreover, candidate genes MMP1, CDC45, and CAT were, respectively, enriched in pathway in cancer, cell cycle, and methane metabolism. Conclusion. Candidate pathogenic genes including MMP1, CDC45, CAT, and VIM might be involved in the pathogenesis of CC. We believe that our results can provide theoretical guidelines for future clinical application.

  20. Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes involved in camptothecin biosynthesis and transport

    Directory of Open Access Journals (Sweden)

    Sun Yongzhen

    2011-10-01

    Full Text Available Abstract Background Camptotheca acuminata is a Nyssaceae plant, often called the "happy tree", which is indigenous in Southern China. C. acuminata produces the terpenoid indole alkaloid, camptothecin (CPT, which exhibits clinical effects in various cancer treatments. Despite its importance, little is known about the transcriptome of C. acuminata and the mechanism of CPT biosynthesis, as only few nucleotide sequences are included in the GenBank database. Results From a constructed cDNA library of young C. acuminata leaves, a total of 30,358 unigenes, with an average length of 403 bp, were obtained after assembly of 74,858 high quality reads using GS De Novo assembler software. Through functional annotation, a total of 21,213 unigenes were annotated at least once against the NCBI nucleotide (Nt, non-redundant protein (Nr, Uniprot/SwissProt, Kyoto Encyclopedia of Genes and Genomes (KEGG, and Arabidopsis thaliana proteome (TAIR databases. Further analysis identified 521 ESTs representing 20 enzyme genes that are involved in the backbone of the CPT biosynthetic pathway in the library. Three putative genes in the upstream pathway, including genes for geraniol-10-hydroxylase (CaPG10H, secologanin synthase (CaPSCS, and strictosidine synthase (CaPSTR were cloned and analyzed. The expression level of the three genes was also detected using qRT-PCR in C. acuminata. With respect to the branch pathway of CPT synthesis, six cytochrome P450s transcripts were selected as candidate transcripts by detection of transcript expression in different tissues using qRT-PCR. In addition, one glucosidase gene was identified that might participate in CPT biosynthesis. For CPT transport, three of 21 transcripts for multidrug resistance protein (MDR transporters were also screened from the dataset by their annotation result and gene expression analysis. Conclusion This study produced a large amount of transcriptome data from C. acuminata by 454 pyrosequencing. According to

  1. Allatostatin-type A, kisspeptin and galanin GPCRs and putative ligands as candidate regulatory factors of mantle function.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Bjärnmark, Nadège; Power, Deborah M

    2016-06-01

    Allatostatin-type A (AST-A), kisspeptin (KISS) and galanin (GAL) G-protein coupled receptor (GPCR) systems share a common ancestral origin in arthropods and the vertebrates where they regulate metabolism and reproduction. The molluscs are the second most diverse phylum in the animal kingdom, they occupy an important phylogenetic position, and their genome is more similar to deuterostomes than the arthropods and nematodes and thus they are good models for studies of gene family evolution and function. This mini-review intends to extend the current knowledge about AST-A, KISS and GAL GPCR system evolution and their putative function in the mollusc mantle. Comparative evolutionary analysis of the target GPCR systems was established by identifying homologues in genomes and tissue transcriptome datasets available for molluscs and comparing them to those of other metazoan systems. Studies in arthropods have revealed the existence of the AST-A system but the loss of homologues of the KISS and GAL systems. Homologues of the insect AST-AR and vertebrate KISSR genes were found in molluscs but putative GALR genes were absent. Receptor gene number suggested that members of this family have suffered lineage specific evolution during the molluscan radiation. In molluscs, orthologues of the insect AST-A peptides were not identified but buccalin peptides that are structurally related were identified and are putative receptor agonists. The identification of AST-AR and KISSR genes in molluscs strengthens the hypotheses that in metazoans members of the AST-AR subfamily share evolutionary proximity with KISSRs. The variable number of receptors and large repertoire of buccalin peptides may be indicative of the functional diversity of the AST-AR/KISSR systems in molluscs. The identification of AST-A and KISS receptors and ligands in the mantle transcriptome indicates that in molluscs they may have acquired a novel function and may play a role in shell development or sensory detection in

  2. Evaluating gene × gene and gene × smoking interaction in rheumatoid arthritis using candidate genes in GAW15

    OpenAIRE

    Mei Ling; Li Xiaohui; Yang Kai; Cui Jinrui; Fang Belle; Guo Xiuqing; Rotter Jerome I

    2007-01-01

    Abstract We examined the potential gene × gene interactions and gene × smoking interactions in rheumatoid arthritis (RA) using the candidate gene data sets provided by Genetic Analysis Workshop 15 Problem 2. The multifactor dimensionality reduction (MDR) method was used to test gene × gene interactions among candidate genes. The case-only sample was used to test gene × smoking interactions. The best predictive model was the single-locus model with single-nucleotide polymorphism (SNP) rs247660...

  3. Mapping of Candidate Genes Involved in Bud Dormancy and Flowering Time in Sweet Cherry (Prunus avium.

    Directory of Open Access Journals (Sweden)

    Sophie Castède

    Full Text Available The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions.

  4. Mapping of Candidate Genes Involved in Bud Dormancy and Flowering Time in Sweet Cherry (Prunus avium).

    Science.gov (United States)

    Castède, Sophie; Campoy, José Antonio; Le Dantec, Loïck; Quero-García, José; Barreneche, Teresa; Wenden, Bénédicte; Dirlewanger, Elisabeth

    2015-01-01

    The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs) associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions. PMID:26587668

  5. Identification of candidate genes for susceptibility to reactive arthritis

    NARCIS (Netherlands)

    M. Rihl; C. Barthel; A. Klos; R.E. Schmidt; P.P. Tak; H. Zeidler; J.G. Kuipers

    2009-01-01

    This study was undertaken to evaluate the gene expression profile in monocytes from three patients with reactive arthritis (ReA) in remission in order to identify candidate genes accounting for a potential susceptibility to ReA. Gene expression analyses revealed eight differentially expressed mRNA t

  6. The Important Candidate Genes in Goats - A Review

    Directory of Open Access Journals (Sweden)

    China SUPAKORN

    2009-01-01

    Full Text Available A total of 271 candidate genes have been detected in goats. However, comprehensive investigations have been carried out on the polymorphism of some genes, involved in the control of economic traits. Candidate genes have an effect on the physiological pathway, metabolism and expression of phenotypes. For growth traits, growth hormone (GH, growth hormone receptor (GHR, insulin like growth factor I (IGF-I, leptin (LEP, caprine pituitary specific transcription factor-1 (POU1F1, caprine myostatin (MSTN and bone morphogenetic protein (BMP genes are necessary for bone formation, birth weight, weaning weight, body condition and muscle growth. For reproduction, forkhead box L 2 (FOXL2, melatonin receptor 1A (MTNR1A, sex determination region of Y chromosome (SRY and amelogenin (AMEL genes influence sex determination and proliferation. The major candidate genes for milk yield and milk composition traits are the casein gene and their family. Keratin associated protein (KAP and melanocortin 1 receptor (MC1R genes are candidate genes for wool traits. The major histocompatibility complex (MHC gene is considered important for the immune system and disease resistance traits. The functions of these genes on economically important traits are different. Some genes have synergistic or antagonistic effects in nature for expression of phenotypic traits. On the other hand, some genes could control more than one trait. Also, the producers should be concerned with these effects because selection of a single trait by using only a gene could affect other traits. Therefore, the identification of candidate genes and their mutations which cause variations of gene expression and phenotype of economic traits will help breeders to search some genetic markers for these economic traits. It may be used as an aid in the selection of parent stock at an early age in the future.

  7. Unifying candidate gene and GWAS Approaches in Asthma.

    Directory of Open Access Journals (Sweden)

    Sven Michel

    Full Text Available The first genome wide association study (GWAS for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing. Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a GWAS coverage is insufficient for many asthma candidate genes, (b imputation based on these data is reliable but incomplete, and (c SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes.

  8. Characterization of Two Putative Protein Phosphatase Genes and Their Involvement in Phosphorus Efficiency in Phaseolus vulgari

    Institute of Scientific and Technical Information of China (English)

    Cui-Yue Liang; Zhi-Jian Chen; Zhu-Fang Yao; Jiang Tian; Hong Liao

    2012-01-01

    Protein dephosphorylation mediated by protein phosphatases plays a major role in signal transduction of plant responses to environmental stresses.In this study,two putative protein phosphatases,PvPS2:1 and PvPS2:2 were identified and characterized in bean (Phaseolus vulgaris).The two PvPS2 members were found to be localized to the plasma membrane and the nucleus by transient expression of PvPS2:GFP in onion epidermal cells.Transcripts of the two PvPS2 genes were significantly increased by phosphate (Pi) starvation in the two bean genotypes,G19833 (a P-efficient genotype) and DOR364 (a P-inefficient genotype).However,G19833 exhibited higher PvPS2:1 expression levels than DOR364 in both leaves and roots during P1 starvation.Increased transcription of PvPS2:1 in response to Pi starvation was further verified through histochemical analysis of PvPS2:1 promoter fusion β-glucuronidase (GUS) in transgenic Arabidopsis plants.Analysis of PvPS2∶1 overexpression lines in bean hairy roots and Arabidopsis showed that PvS2:1 was involved in root growth and P accumulation.Furthermore,expression levels of two P(1) starvation responsive genes were upregulated and the APase activities were enhanced in the overexpressing PvPS2∶1 Arabidopsis lines.Taken together,our results strongly suggested that PvPS2∶1positively regulated plant responses to P1 starvation,and could be further targeted as a candidate gene to improve crop P efficiency.

  9. Using the candidate gene approach for detecting genes underlying seed oil concentration and yield in soybean.

    Science.gov (United States)

    Eskandari, Mehrzad; Cober, Elroy R; Rajcan, Istvan

    2013-07-01

    Increasing the oil concentration in soybean seeds has been given more attention in recent years because of demand for both edible oil and biodiesel production. Oil concentration in soybean is a complex quantitative trait regulated by many genes as well as environmental conditions. To identify genes governing seed oil concentration in soybean, 16 putative candidate genes of three important gene families (GPAT: acyl-CoA:sn-glycerol-3-phosphate acyltransferase, DGAT: acyl-CoA:diacylglycerol acyltransferase, and PDAT: phospholipid:diacylglycerol acyltransferase) involved in triacylglycerol (TAG) biosynthesis pathways were selected and their sequences retrieved from the soybean database ( http://www.phytozome.net/soybean ). Three sequence mutations were discovered in either coding or noncoding regions of three DGAT soybean isoforms when comparing the parents of a 203 recombinant inbreed line (RIL) population; OAC Wallace and OAC Glencoe. The RIL population was used to study the effects of these mutations on seed oil concentration and other important agronomic and seed composition traits, including seed yield and protein concentration across three field locations in Ontario, Canada, in 2009 and 2010. An insertion/deletion (indel) mutation in the GmDGAT2B gene in OAC Wallace was significantly associated with reduced seed oil concentration across three environments and reduced seed yield at Woodstock in 2010. A mutation in the 3' untranslated (3'UTR) region of GmDGAT2C was associated with seed yield at Woodstock in 2009. A mutation in the intronic region of GmDGAR1B was associated with seed yield and protein concentration at Ottawa in 2010. The genes identified in this study had minor effects on either seed yield or oil concentration, which was in agreement with the quantitative nature of the traits. However, the novel gene-specific markers designed in the present study can be used in soybean breeding for marker-assisted selection aimed at increasing seed yield and oil

  10. Using the candidate gene approach for detecting genes underlying seed oil concentration and yield in soybean.

    Science.gov (United States)

    Eskandari, Mehrzad; Cober, Elroy R; Rajcan, Istvan

    2013-07-01

    Increasing the oil concentration in soybean seeds has been given more attention in recent years because of demand for both edible oil and biodiesel production. Oil concentration in soybean is a complex quantitative trait regulated by many genes as well as environmental conditions. To identify genes governing seed oil concentration in soybean, 16 putative candidate genes of three important gene families (GPAT: acyl-CoA:sn-glycerol-3-phosphate acyltransferase, DGAT: acyl-CoA:diacylglycerol acyltransferase, and PDAT: phospholipid:diacylglycerol acyltransferase) involved in triacylglycerol (TAG) biosynthesis pathways were selected and their sequences retrieved from the soybean database ( http://www.phytozome.net/soybean ). Three sequence mutations were discovered in either coding or noncoding regions of three DGAT soybean isoforms when comparing the parents of a 203 recombinant inbreed line (RIL) population; OAC Wallace and OAC Glencoe. The RIL population was used to study the effects of these mutations on seed oil concentration and other important agronomic and seed composition traits, including seed yield and protein concentration across three field locations in Ontario, Canada, in 2009 and 2010. An insertion/deletion (indel) mutation in the GmDGAT2B gene in OAC Wallace was significantly associated with reduced seed oil concentration across three environments and reduced seed yield at Woodstock in 2010. A mutation in the 3' untranslated (3'UTR) region of GmDGAT2C was associated with seed yield at Woodstock in 2009. A mutation in the intronic region of GmDGAR1B was associated with seed yield and protein concentration at Ottawa in 2010. The genes identified in this study had minor effects on either seed yield or oil concentration, which was in agreement with the quantitative nature of the traits. However, the novel gene-specific markers designed in the present study can be used in soybean breeding for marker-assisted selection aimed at increasing seed yield and oil

  11. Putative resistance genes in the CitEST database

    Directory of Open Access Journals (Sweden)

    Simone Guidetti-Gonzalez

    2007-01-01

    Full Text Available Disease resistance in plants is usually associated with the activation of a wide variety of defense responses to prevent pathogen replication and/or movement. The ability of the host plant to recognize the pathogen and to activate defense responses is regulated by direct or indirect interaction between the products of plant resistance (R and pathogen avirulence (Avr genes. Attempted infection of plants by avirulent pathogens elicits a battery of defenses often followed by the collapse of the challenged host cells. Localized host cell death may help to prevent the pathogen from spreading to uninfected tissues, known as hypersensitive response (HR. When either the plant or the pathogen lacks its cognate gene, activation of the plant’s defense responses fails to occur or is delayed and does not prevent pathogen colonization. In the CitEST database, we identified 1,300 reads related to R genes in Citrus which have been reported in other plant species. These reads were translated in silico, and alignments of their amino acid sequences revealed the presence of characteristic domains and motifs that are specific to R gene classes. The description of the reads identified suggests that they function as resistance genes in citrus.

  12. Identification of quantitative trait loci and candidate genes for cadmium tolerance in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Induri, Brahma R [West Virginia University; Ellis, Danielle R [West Virginia University; Slavov, Goncho T. [West Virginia University; Yin, Tongming [ORNL; Zhang, Xinye [ORNL; Tuskan, Gerald A [ORNL; DiFazio, Steven P [West Virginia University

    2012-01-01

    Understanding genetic variation for the response of Populus to heavy metals like cadmium (Cd) is an important step in elucidating the underlying mechanisms of tolerance. In this study, a pseudo-backcross pedigree of Populus trichocarpa Torr. & Gray and Populus deltoides Bart. was characterized for growth and performance traits after Cd exposure. A total of 16 quantitative trait loci (QTL) at logarithm of odds (LOD) ratio 2.5 were detected for total dry weight, its components and root volume. Major QTL for Cd responses were mapped to two different linkage groups and the relative allelic effects were in opposing directions on the two chromosomes, suggesting differential mechanisms at these two loci. The phenotypic variance explained by Cd QTL ranged from 5.9 to 11.6% and averaged 8.2% across all QTL. A whole-genome microarray study led to the identification of nine Cd-responsive genes from these QTL. Promising candidates for Cd tolerance include an NHL repeat membrane-spanning protein, a metal transporter and a putative transcription factor. Additional candidates in the QTL intervals include a putative homolog of a glutamate cysteine ligase, and a glutathione-S-transferase. Functional characterization of these candidate genes should enhance our understanding of Cd metabolism and transport and phytoremediation capabilities of Populus.

  13. Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Nielsen, Mette Gilling

    Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...

  14. Candidate gene studies in human anxiety disorders

    OpenAIRE

    Donner, Jonas

    2012-01-01

    Anxiety disorders, such as panic disorder (PD), obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and phobias are common psychiatric disorders, characterized by exaggerated, prolonged and debilitating levels of anxiety. They are complex diseases with onset influenced by both environmental and genetic factors, but so far little progress has been made in identifying solid susceptibility genes. The aim of this study was to shed light on the genetic basi...

  15. Identification of putative gene based markers of renal toxicity.

    OpenAIRE

    Amin, Rupesh P; Vickers, Alison E; Sistare, Frank; Thompson, Karol L.; Roman, Richard J.; Lawton, Michael; Kramer, Jeffrey; Hamadeh, Hisham K.; Collins, Jennifer; Grissom, Sherry; Bennett, Lee; Tucker, C Jeffrey; Wild, Stacie; Kind, Clive; Oreffo, Victor

    2004-01-01

    This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for...

  16. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

    Indian Academy of Sciences (India)

    N. Johns; B. H. Tan; M. Macmillan; T. S. Solheim; J. A. Ross; V. E. Baracos; S. Damaraju; K. C. H. Fearon

    2014-12-01

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  17. Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

    Science.gov (United States)

    The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

  18. Identification of genes from the Treacher Collins candidate region

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, M.; Dixon, J.; Edwards, S. [Univ. of California, Irvine, CA (United States)]|[Univ. of Manchester (United Kingdom)] [and others

    1994-09-01

    Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development. The TCOF1 locus has previously been mapped to chromosome 5q32-33. The candidate gene region has been defined as being between two flanking markers, ribosomal protein S14 (RPS14) and Annexin 6 (ANX6), by analyzing recombination events in affected individuals. It is estimated that the distance between these flanking markers is 500 kb by three separate analysis methods: (1) radiation hybrid mapping; (2) genetic linkage; and (3) YAC contig analysis. A cosmid contig which spans the candidate gene region for TCOF1 has been constructed by screening the Los Alamos National Laboratory flow-sorted chromosome 5 cosmid library. Cosmids were obtained by using a combination of probes generated from YAC end clones, Alu-PCR fragments from YACs, and asymmetric PCR fragments from both T7 and T3 cosmid ends. Exon amplifications, the selection of genomic coding sequences based upon the presence of functional splice acceptor and donor sites, was used to identify potential exon sequences. Sequences found to be conserved between species were then used to screen cDNA libraries in order to identify candidate genes. To date, four different cDNAs have been isolated from this region and are being analyzed as potential candidate genes for TCOF1. These include the genes encoding plasma glutathione peroxidase (GPX3), heparin sulfate sulfotransferase (HSST), a gene with homology to the ETS family of proteins and one which shows no homology to any known genes. Work is also in progress to identify and characterize additional cDNAs from the candidate gene region.

  19. Oligonucleotide conjugates - Candidates for gene silencing therapeutics.

    Science.gov (United States)

    Gooding, Matt; Malhotra, Meenakshi; Evans, James C; Darcy, Raphael; O'Driscoll, Caitriona M

    2016-10-01

    The potential therapeutic and diagnostic applications of oligonucleotides (ONs) have attracted great attention in recent years. The capability of ONs to selectively inhibit target genes through antisense and RNA interference mechanisms, without causing un-intended sideeffects has led them to be investigated for various biomedical applications, especially for the treatment of viral diseases and cancer. In recent years, many researchers have focused on enhancing the stability and target specificity of ONs by encapsulating/complexing them with polymers or lipid chains to formulate nanoparticles/nanocomplexes/micelles. Also, chemical modification of nucleic acids has emerged as an alternative to impart stability to ONs against nucleases and other degrading enzymes and proteins found in blood. In addition to chemically modifying the nucleic acids directly, another strategy that has emerged, involves conjugating polymers/peptide/aptamers/antibodies/proteins, preferably to the sense strand (3'end) of siRNAs. Conjugation to the siRNA not only enhances the stability and targeting specificity of the siRNA, but also allows for the development of self-administering siRNA formulations, with a much smaller size than what is usually observed for nanoparticle (∼200nm). This review concentrates mainly on approaches and studies involving ON-conjugates for biomedical applications. PMID:27521696

  20. Candidate genes of idiopathic pulmonary fibrosis: current evidence and research

    Directory of Open Access Journals (Sweden)

    Zhou W

    2016-02-01

    Full Text Available Wei Zhou,1,2 Yaping Wang1,2 1Department of Medical Genetics, 2Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, People's Republic of China Abstract: Idiopathic pulmonary fibrosis (IPF is a group of common and lethal forms of idiopathic interstitial pulmonary disease. IPF is characterized by a progressive decline in lung function with a median survival of 2–3 years after diagnosis. Although the pathogenesis of the disease remains unknown, genetic predisposition could play a causal role in IPF. A set of genes have been identified as candidate genes of IPF in the past 20 years. However, the recent technological advances that allow for the analysis of millions of polymorphisms in different subjects have deepened the understanding of the genetic complexity of IPF susceptibility. Genome-wide association studies and whole-genome sequencing continue to reveal the genetic loci associated with IPF risk. In this review, we describe candidate genes on the basis of their functions and aim to gain a better understanding of the genetic basis of IPF. The discovered candidate genes may help to clarify pivotal aspects in the diagnosis, prognosis, and therapies of IPF. Keywords: idiopathic pulmonary fibrosis, candidate genes, susceptibility 

  1. Influence of putative exopolysaccharide genes on Pseudomonas putida KT2440 biofilm stability

    DEFF Research Database (Denmark)

    Nilsson, Martin; Chiang, Wen-Chi; Fazli, Mustafa;

    2011-01-01

    We report a study of the role of putative exopolysaccharide gene clusters in the formation and stability of Pseudomonas putida KT2440 biofilm. Two novel putative exopolysaccharide gene clusters, pea and peb, were identified, and evidence is provided that they encode products that stabilize P....... putida KT2440 biofilm. The gene clusters alg and bcs, which code for proteins mediating alginate and cellulose biosynthesis, were found to play minor roles in P. putida KT2440 biofilm formation and stability under the conditions tested. A P. putida KT2440 derivative devoid of any identifiable...... exopolysaccharide genes was found to form biofilm with a structure similar to wild-type biofilm, but with a stability lower than that of wild-type biofilm. Based on our data, we suggest that the formation of structured P. putida KT2440 biofilm can occur in the absence of exopolysaccharides; however...

  2. Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes

    DEFF Research Database (Denmark)

    Russell, Meaghan K; Longoni, Mauro; Wells, Julie;

    2012-01-01

    perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes...... expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental...... previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously...

  3. Cloning and molecular characterization of a putative voltage-gated sodium channel gene in the crayfish.

    Science.gov (United States)

    Coskun, Cagil; Purali, Nuhan

    2016-06-01

    Voltage-gated sodium channel genes and associated proteins have been cloned and studied in many mammalian and invertebrate species. However, there is no data available about the sodium channel gene(s) in the crayfish, although the animal has frequently been used as a model to investigate various aspects of neural cellular and circuit function. In the present work, by using RNA extracts from crayfish abdominal ganglia samples, the complete open reading frame of a putative sodium channel gene has firstly been cloned and molecular properties of the associated peptide have been analyzed. The open reading frame of the gene has a length of 5793 bp that encodes for the synthesis of a peptide, with 1930 amino acids, that is 82% similar to the α-peptide of a sodium channel in a neighboring species, Cancer borealis. The transmembrane topology analysis of the crayfish peptide indicated a pattern of four folding domains with several transmembrane segments, as observed in other known voltage-gated sodium channels. Upon analysis of the obtained sequence, functional regions of the putative sodium channel responsible for the selectivity filter, inactivation gate, voltage sensor, and phosphorylation have been predicted. The expression level of the putative sodium channel gene, as defined by a qPCR method, was measured and found to be the highest in nervous tissue. PMID:27032955

  4. Identification of candidate genes for dyslexia susceptibility on chromosome 18.

    Directory of Open Access Journals (Sweden)

    Thomas S Scerri

    Full Text Available Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s conferring susceptibility by a two stage strategy of linkage and association analysis.Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R, dymeclin (DYM and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L.Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

  5. Candidate olfaction genes identified within the Helicoverpa armigera Antennal Transcriptome.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available Antennal olfaction is extremely important for insect survival, mediating key behaviors such as host preference, mate choice, and oviposition site selection. Multiple antennal proteins are involved in olfactory signal transduction pathways. Of these, odorant receptors (ORs and ionotropic receptors (IRs confer specificity on olfactory sensory neuron responses. In this study, we identified the olfactory gene repertoire of the economically important agricultural pest moth, Helicoverpa armigera, by assembling the adult male and female antennal transcriptomes. Within the male and female antennal transcriptomes we identified a total of 47 OR candidate genes containing 6 pheromone receptor candidates. Additionally, 12 IR genes as well as 26 odorant-binding proteins and 12 chemosensory proteins were annotated. Our results allow a systematic functional analysis across much of conventional ORs repertoire and newly reported IRs mediating the key olfaction-mediated behaviors of H. armigera.

  6. Retinoblastoma-associated protein 140 as a candidate for a novel etiological gene to hypertension.

    Science.gov (United States)

    Crespo, Kimberley; Ménard, Annie; Deng, Alan Y

    2016-01-01

    Gene discovery in animal models may lead to the revelation of therapeutic targets for essential hypertension as well as mechanistic insights into blood pressure (BP) regulation. Our aim was to identify a disease-causing gene for a component of polygenic hypertension contrasting inbred hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats. The chromosome segment harboring a quantitative trait locus (QTL), C16QTL, was first isolated from the rat genome via congenic strains. A candidate gene responsible for C16QTL causing a BP difference between DSS and Lewis rats was then identified using molecular analyses combining our independently-conducted total genome and gene-specific sequencings. The retinoblastoma-associated protein 140 (Rap140)/family with sequence similarity 208 member A (Fam208a) is the only candidate gene supported to be C16QTL among three genes in genome block 1 present in the C16QTL-residing interval. A mode of its actions could be to influence the expressions of genes that are downstream in a pathway potentially leading to BP regulation such as that encoding the solute carrier family 7 (cationic amino acid transporter, y+ system) member 12 (Slc7a12), which is specifically expressed in kidneys. Thus, Rap140/Fam208a probably encoding a transcription factor is the strongest candidate for a novel BP QTL that acts via a putative Rap140/Fam208a-Slc7a12-BP pathway. These data implicate a premier physiological role for Rap140/Fam208 beyond development and a first biological function for the Slc7a12 protein in any organism. PMID:27391979

  7. Transcriptomic analysis using olive varieties and breeding progenies identify candidate genes involved in plant architecture

    Directory of Open Access Journals (Sweden)

    Juan José eGonzález Plaza

    2016-03-01

    Full Text Available Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2,252 differentially expressed genes associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  8. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  9. QTLs and candidate genes for desiccation and abscisic acid content in maize kernels

    Directory of Open Access Journals (Sweden)

    Charcosset Alain

    2010-01-01

    Full Text Available Abstract Background Kernel moisture at harvest is an important trait since a low value is required to prevent unexpected early germination and ensure seed preservation. It is also well known that early germination occurs in viviparous mutants, which are impaired in abscisic acid (ABA biosynthesis. To provide some insight into the genetic determinism of kernel desiccation in maize, quantitative trait loci (QTLs were detected for traits related to kernel moisture and ABA content in both embryo and endosperm during kernel desiccation. In parallel, the expression and mapping of genes involved in kernel desiccation and ABA biosynthesis, were examined to detect candidate genes. Results The use of an intermated recombinant inbred line population allowed for precise QTL mapping. For 29 traits examined in an unreplicated time course trial of days after pollination, a total of 78 QTLs were detected, 43 being related to kernel desiccation, 15 to kernel weight and 20 to ABA content. Multi QTL models explained 35 to 50% of the phenotypic variation for traits related to water status, indicating a large genetic control amenable to breeding. Ten of the 20 loci controlling ABA content colocated with previously detected QTLs controlling water status and ABA content in water stressed leaves. Mapping of candidate genes associated with kernel desiccation and ABA biosynthesis revealed several colocations between genes with putative functions and QTLs. Parallel investigation via RT-PCR experiments showed that the expression patterns of the ABA-responsive Rab17 and Rab28 genes as well as the late embryogenesis abundant Emb5 and aquaporin genes were related to desiccation rate and parental allele effect. Database searches led to the identification and mapping of two zeaxanthin epoxidase (ZEP and five novel 9-cis-epoxycarotenoid dioxygenase (NCED related genes, both gene families being involved in ABA biosynthesis. The expression of these genes appeared independent in

  10. Speeding disease gene discovery by sequence based candidate prioritization

    Directory of Open Access Journals (Sweden)

    Porteous David J

    2005-03-01

    Full Text Available Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

  11. No Evidence for Association between Amelogenesis Imperfecta and Candidate Genes

    Directory of Open Access Journals (Sweden)

    M Ghandehari Motlagh

    2009-03-01

    Full Text Available "nBackground: Amelogenesis imperfecta (AI is an inherited tooth disorder. Despite the fact that up to now, several gene muta­tions in MMP20, ENAM, AMELX and KLK4 genes have been reported to be associated with AI, many other genes sug­gested to be involved. The main objective of this study was to find the mutations in three major candidate genes including MMP20, ENAM and KLK4 responsible for AI from three Iranian families with generalized hypoplastic phenotype in all teeth. "nMethods: All exon/intron boundaries of subjected genes were amplified by polymerase chain reaction and subjected to direct sequencing."nResults: One polymorphisms was identified in KLK4 exon 2, in one family a homozygous mutation was found in the third base of codon 22 for serine (TCG>TCT, but not in other families. Although these base substitutions have been occurred in the signaling domain, they do not seem to influence the activity of KLK4 protein."nConclusion: Our results might support the further evidence for genetic heterogeneity; at least, in some AI cases are not caused by a gene in these reported candidate genes.

  12. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne;

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  13. Putative cis-regulatory elements in genes highly expressed in rice sperm cells

    Directory of Open Access Journals (Sweden)

    Singh Mohan B

    2011-09-01

    Full Text Available Abstract Background The male germ line in flowering plants is initiated within developing pollen grains via asymmetric division. The smaller cell then becomes totally encased within a much larger vegetative cell, forming a unique "cell within a cell structure". The generative cell subsequently divides to give rise to two non-motile diminutive sperm cells, which take part in double fertilization and lead to the seed set. Sperm cells are difficult to investigate because of their presence within the confines of the larger vegetative cell. However, recently developed techniques for the isolation of rice sperm cells and the fully annotated rice genome sequence have allowed for the characterization of the transcriptional repertoire of sperm cells. Microarray gene expression data has identified a subset of rice genes that show unique or highly preferential expression in sperm cells. This information has led to the identification of cis-regulatory elements (CREs, which are conserved in sperm-expressed genes and are putatively associated with the control of cell-specific expression. Findings We aimed to identify the CREs associated with rice sperm cell-specific gene expression data using in silico prediction tools. We analyzed 1-kb upstream regions of the top 40 sperm cell co-expressed genes for over-represented conserved and novel motifs. Analysis of upstream regions with the SIGNALSCAN program with the PLACE database, MEME and the Mclip tool helped to find combinatorial sets of known transcriptional factor-binding sites along with two novel motifs putatively associated with the co-expression of sperm cell-specific genes. Conclusions Our data shows the occurrence of novel motifs, which are putative CREs and are likely targets of transcriptional factors regulating sperm cell gene expression. These motifs can be used to design the experimental verification of regulatory elements and the identification of transcriptional factors that regulate sperm cell

  14. Tagging Blast Resistance Gene Pi 1 in Rice (Oryza sativa) Using Candidate Resistance Genes

    Institute of Scientific and Technical Information of China (English)

    LI Ai-hong; WU Jian-li; XU Xin-ping; Menchu BERNADO; DAI Zheng-yuan; ZHUANG Jie-yun; CHEN Zong-xiang; ZHENG Kang-le; LI Bao-jian; Hei LEUNG; ZHANG Hong-xi; PAN Xue-biao

    2004-01-01

    An F3 population derived from C101LAC/CO39 containing 90 lines was analyzed for blast resistance with 48 candidate genes developed from resistance gene analogs (RGA) and suppression subtractive library. Genetic analysis confirmed that blast resistance of the population was controlled by a single gene Pi 1. One of the candidate genes, R10 was identified as associated with the blast resistance gene on the long arm of chromosome 11 and mapped using a DH population derived from Azucena/IR64.A pair of PCR based primers was designed based on the sequence of R10 for marker-aided selection of the blast resistance gene.The recombination frequency between Pi 1 and the marker was estimated as 1.28%. It suggested that strategy of employing candidate genes is useful for gene identification and mapping. A new RFLP marker and the corresponding PCR marker for tagging of Pi 1 were provided.

  15. Genetics of osteoporosis: searching for candidate genes for bone fragility.

    Science.gov (United States)

    Rocha-Braz, Manuela G M; Ferraz-de-Souza, Bruno

    2016-08-01

    The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype. PMID:27533615

  16. Genetics of intracerebral hemorrhage: Insights from candidate gene approaches

    OpenAIRE

    Baoqiong Liu; Le Zhang; Qidong Yang

    2012-01-01

    Intracerebral hemorrhage (ICH) is a heterogeneous disease with genetic factors playing an important role. Association studies on a wide range of candidate pathways suggest a weak but significant effect for several alleles with ICH risk. Among the most widely investigated genes are those involved in the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme), coagulation pathway (e.g., Factor XIII, Factor VII, platelet-activating factor acetylhydrolase, Factor V Leiden, and ...

  17. Association of candidate genes with antisocial drug dependence in adolescents

    OpenAIRE

    Corley, Robin P.; Zeiger, Joanna S.; Crowley, Thomas; Ehringer, Marissa A.; Hewitt, John K.; Christian J Hopfer; Lessem, Jeffrey; McQueen, Matthew B.; Rhee, Soo Hyun; Smolen, Andrew; Stallings, Michael C.; Young, Susan E.; Krauter, Kenneth

    2008-01-01

    The Colorado Center for Antisocial Drug Dependence (CADD) is using several research designs and strategies in its study of the genetic basis for antisocial drug dependence in adolescents. This study reports Single Nucleotide Polymorphism (SNP) association results from a Targeted Gene Assay (SNP chip) of 231 Caucasian male probands in treatment with antisocial drug dependence and a matched set of community controls. The SNP chip was designed to assay 1500 SNPs distributed across 50 candidate g...

  18. Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

    Directory of Open Access Journals (Sweden)

    Luo Hongmei

    2011-12-01

    Full Text Available Abstract Background Panax notoginseng (Burk F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. Results Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS, which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158 and UDP-glycosyltransferase (Pn00082 gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH, and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. Conclusion This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next

  19. Duplications and losses in gene families of rust pathogens highlight putative effectors

    Directory of Open Access Journals (Sweden)

    Amanda L. Pendleton

    2014-06-01

    Full Text Available Rust fungi are a group of fungal pathogens that cause some of the world’s most destructive diseases of trees and crops. A shared characteristic among rust fungi is obligate biotrophy, the inability to complete a lifecycle without a host. This dependence on a host species likely affects patterns of gene expansion, contraction, and innovation within rust pathogen genomes. The establishment of disease by biotrophic pathogens is reliant upon effector proteins that are encoded in the fungal genome and secreted from the pathogen into the host’s cell apoplast or within the cells. This study uses a comparative genomic approach to elucidate putative effectors and determine their evolutionary histories. We used OrthoMCL to identify nearly 20,000 gene families in proteomes of sixteen diverse fungal species, which include fifteen basidiomycetes and one ascomycete. We inferred patterns of duplication and loss for each gene family and identified families with distinctive patterns of expansion/contraction associated with the evolution of rust fungal genomes. To recognize potential contributors for the unique features of rust pathogens, we identified families harboring secreted proteins that: i arose or expanded in rust pathogens relative to other fungi, or ii contracted or were lost in rust fungal genomes. While the origin of rust fungi appears to be associated with considerable gene loss, there are many gene duplications associated with each sampled rust fungal genome. We also highlight two putative effector gene families that have expanded in Cqf that we hypothesize have roles in pathogenicity.

  20. Transcriptome Analysis Reveals Putative Genes Involved in Iridoid Biosynthesis in Rehmannia glutinosa

    Directory of Open Access Journals (Sweden)

    Xianen Li

    2012-10-01

    Full Text Available Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R. glutinosa and investigate genes involved in iridoid biosynthesis, we used massively parallel pyrosequencing on the 454 GS FLX Titanium platform to generate a substantial EST dataset. Based on sequence similarity searches against the public sequence databases, the sequences were first annotated and then subjected to Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG based analysis. Bioinformatic analysis indicated that the 454 assembly contained a set of genes putatively involved in iridoid biosynthesis. Significantly, homologues of the secoiridoid pathway genes that were only identified in terpenoid indole alkaloid producing plants were also identified, whose presence implied that route II iridoids and route I iridoids share common enzyme steps in the early stage of biosynthesis. The gene expression patterns of four prenyltransferase transcripts were analyzed using qRT-PCR, which shed light on their putative functions in tissues of R. glutinosa. The data explored in this study will provide valuable information for further studies concerning iridoid biosynthesis.

  1. Identification of putative circadian clock genes in the American horseshoe crab, Limulus polyphemus.

    Science.gov (United States)

    Chesmore, Kevin N; Watson, Winsor H; Chabot, Christopher C

    2016-09-01

    While the American horseshoe crab, Limulus polyphemus, has robust circadian and circatidal rhythms, virtually nothing is known about the molecular basis of these rhythms in this species or any other chelicerate. In this study, next generation sequencing was used to assemble transcriptomic reads and then putative homologs of known core and accessory circadian genes were identified in these databases. Homologous transcripts were discovered for one circadian clock input gene, five core genes, 22 accessory genes, and two possible output pathways. Alignments and functional domain analyses showed generally high conservation between the putative L. polyphemus clock genes and homologs from Drosophila melanogaster and Daphnia pulex. The presence of both cry1 and cry2 in the L. polyphemus transcriptome would classify its system as an "ancestral", type 2 clock system. In addition, a novel duplication of CYCLE, and a novel triplication of PERIOD were found. Investigations are currently underway to determine if any of these "circadian" genes also participate in the molecular processes that drive the Limulus circatidal clock. PMID:27341138

  2. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S;

    2011-01-01

    The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere...... as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a...

  3. Identification of a Putative Tetrasporophyte-Specific Gene in Gracilaria lemaneiformis(Gracilariales, Rhodophyte)

    Institute of Scientific and Technical Information of China (English)

    REN Xueying; ZHANG Xuecheng

    2008-01-01

    A putative tetrasporophyte-specific gene, designated as SSH466 (GenBank accession No. DQ019223), was one of the genes identified in this work using suppression subtractive hybridization (SSH) method in Gracilaria lemaneiformis. The full length of the gene was obtained using SMART RACE strategy. Sequence analysis revealed that the gene had 1 019 nucleotides, including an open reading frame of 498 nucleotides encoding 166 amino acid residues, 158 nucleotides of 5' untranslated region and 363 nucleo- tides of 3' non-coding region. Protein motif and secondary structure prediction showed that there existed a transmembrane domain with a unique β-sheet. Thus, SSH466 protein might be a cross-membrane protein. Sequence homology search in the public GenBank databases did not reveal any significant match with SSH466. Virtual Northern blot analysis confirmed that it was a tetrasporo- phyte-specific gene.

  4. Identification of a putative tetrasporophyte-specific gene in Gracilaria lemaneiformis (Gracilariales, Rhodophyte)

    Science.gov (United States)

    Ren, Xueying; Zhang, Xuecheng

    2008-08-01

    A putative tetrasporophyte-specific gene, designated as SSH466 (GenBank accession No. DQ019223), was one of the genes identified in this work using suppression subtractive hybridization (SSH) method in Gracilaria lemaneiformis. The full length of the gene was obtained using SMART RACE strategy. Sequence analysis revealed that the gene had 1 019 nucleotides, including an open reading frame of 498 nucleotides encoding 166 amino acid residues, 158 nucleotides of 5' untranslated region and 363 nucleotides of 3' non-coding region. Protein motif and secondary structure prediction showed that there existed a transmembrane domain with a unique β-sheet. Thus, SSH466 protein might be a cross-membrane protein. Sequence homology search in the public GenBank databases did not reveal any significant match with SSH466. Virtual Northern blot analysis confirmed that it was a tetrasporophyte-specific gene.

  5. Annual Killifish Transcriptomics and Candidate Genes for Metazoan Diapause.

    Science.gov (United States)

    Thompson, Andrew W; Ortí, Guillermo

    2016-09-01

    Dormancy has evolved in all major metazoan lineages. It is critical for survival when environmental stresses are not conducive to growth, maturation, or reproduction. Embryonic diapause is a form of dormancy where development is reversibly delayed and metabolism is depressed. We report the diapause transcriptome of the annual killifish Nematolebias whitei, and compare gene expression between diapause embryos and free-living larvae to identify a candidate set of 945 differentially expressed "diapause" genes for this species. Similarity of transcriptional patterns among N. whitei and other diapausing animals is striking for a small set of genes associated with stress resistance, circadian rhythm, and metabolism, while other genes show discordant patterns. Although convergent evolution of diapause may require shared molecular mechanisms for fundamental processes, similar physiological phenotypes also may arise through modification of alternative pathways. Annual killifishes are a tractable model system for comparative transcriptomic studies on the evolution of diapause. PMID:27297470

  6. Candidate gene analysis of GH1 for effects on growth and carcass composition of cattle.

    Science.gov (United States)

    Taylor, J F; Coutinho, L L; Herring, K L; Gallagher, D S; Brenneman, R A; Burney, N; Sanders, J O; Turner, J W; Smith, S B; Miller, R K; Savell, J W; Davis, S K

    1998-06-01

    We present an approach to evaluate the support for candidate genes as quantitative trait loci (QTLs) within the context of genome-wide map-based cloning strategies. To establish candidacy, a bacterial artificial chromosome (BAC) clone containing a putative candidate gene is physically assigned to an anchored linkage map to localise the gene relative to an identified QTL effect. Microsatellite loci derived from BAC clones containing an established candidate gene are integrated into the linkage map facilitating the evaluation by interval analysis of the statistical support for QTL identity. Permutation analysis is employed to determine experiment-wise statistical support. The approach is illustrated for the growth hormone 1 (GH1) gene and growth and carcass phenotypes in cattle. Polymerase chain reaction (PCR) primers which amplify a 441 bp fragment of GH1 were used to systematically screen a bovine BAC library comprising 60,000 clones and with a 95% probability of containing a single copy sequence. The presence of GH1 in BAC-110R2C3 was confirmed by sequence analysis of the PCR product from this clone and by the physical assignment of BAC110R2C3 to bovine chromosome 19 (BTA19) band 22 by fluorescence in situ hybridisation (FISH). Microsatellite KHGH1 was isolated from BAC110R2C3 and scored in 529 reciprocal backcross and F2 fullsib progeny from 41 resource families derived from Angus (Bos taurus) and Brahman (Bos indicus). The microsatellite KHGH1 was incorporated into a framework genetic map of BTA19 comprising 12 microsatellite loci, the erythrocyte antigen T and a GH1-TaqI restriction fragment length polymorphism (RFLP). Interval analysis localised effects of taurus vs. indicus alleles on subcutaneous fat and the percentage of either extractable fat from the Iongissimus dorsi muscle to the region of BTA19 harbouring GH1.

  7. Candidate gene analysis of GH1 for effects on growth and carcass composition of cattle.

    Science.gov (United States)

    Taylor, J F; Coutinho, L L; Herring, K L; Gallagher, D S; Brenneman, R A; Burney, N; Sanders, J O; Turner, J W; Smith, S B; Miller, R K; Savell, J W; Davis, S K

    1998-06-01

    We present an approach to evaluate the support for candidate genes as quantitative trait loci (QTLs) within the context of genome-wide map-based cloning strategies. To establish candidacy, a bacterial artificial chromosome (BAC) clone containing a putative candidate gene is physically assigned to an anchored linkage map to localise the gene relative to an identified QTL effect. Microsatellite loci derived from BAC clones containing an established candidate gene are integrated into the linkage map facilitating the evaluation by interval analysis of the statistical support for QTL identity. Permutation analysis is employed to determine experiment-wise statistical support. The approach is illustrated for the growth hormone 1 (GH1) gene and growth and carcass phenotypes in cattle. Polymerase chain reaction (PCR) primers which amplify a 441 bp fragment of GH1 were used to systematically screen a bovine BAC library comprising 60,000 clones and with a 95% probability of containing a single copy sequence. The presence of GH1 in BAC-110R2C3 was confirmed by sequence analysis of the PCR product from this clone and by the physical assignment of BAC110R2C3 to bovine chromosome 19 (BTA19) band 22 by fluorescence in situ hybridisation (FISH). Microsatellite KHGH1 was isolated from BAC110R2C3 and scored in 529 reciprocal backcross and F2 fullsib progeny from 41 resource families derived from Angus (Bos taurus) and Brahman (Bos indicus). The microsatellite KHGH1 was incorporated into a framework genetic map of BTA19 comprising 12 microsatellite loci, the erythrocyte antigen T and a GH1-TaqI restriction fragment length polymorphism (RFLP). Interval analysis localised effects of taurus vs. indicus alleles on subcutaneous fat and the percentage of either extractable fat from the Iongissimus dorsi muscle to the region of BTA19 harbouring GH1. PMID:9720178

  8. Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis.

    Science.gov (United States)

    Frasson, Amanda Piccoli; Dos Santos, Odelta; Meirelles, Lúcia Collares; Macedo, Alexandre José; Tasca, Tiana

    2016-01-01

    Trichomonas vaginalis is a protozoan that parasitizes the human urogenital tract causing trichomoniasis, the most common non-viral sexually transmitted disease. The parasite has unique genomic characteristics such as a large genome size and expanded gene families. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is an enzyme responsible for hydrolyzing nucleoside tri- and diphosphates and has already been biochemically characterized in T. vaginalis. Considering the important role of this enzyme in the production of extracellular adenosine for parasite uptake, we evaluated the gene expression of five putative NTPDases in T. vaginalis. We showed that all five putative TvNTPDase genes (TvNTPDase1-5) were expressed by both fresh clinical and long-term grown isolates. The amino acid alignment predicted the presence of the five crucial apyrase conserved regions, transmembrane domains, signal peptides, phosphorylation and catalytic sites. Moreover, a phylogenetic analysis showed that TvNTPDase sequences make up a clade with NTPDases intracellularly located. Biochemical NTPDase activity (ATP and ADP hydrolysis) is responsive to the serum-restrictive conditions and the gene expression of TvNTPDases was mostly increased, mainly TvNTPDase2 and TvNTPDase4, although there was not a clear pattern of expression among them. In summary, the present report demonstrates the gene expression patterns of predicted NTPDases in T. vaginalis.

  9. Genetic Variation in Candidate Genes Like the HMGA2 Gene in the Extremely Tall

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Brown, M. R.; Boot, A. M.; Oostra, B. A.; Drop, S. L. S.; Parks, J. S.

    2011-01-01

    Background/Aims: Genetic variation in several candidate genes has been associated with short stature. Recently, a high-mobility group A2 (HMGA2) gene SNP has been robustly associated with height in the general population. Only few have attempted to study these genes in extremely tall stature. We the

  10. Comparative and genetic analyses of the putative Vibrio cholerae lipopolysaccharide core oligosaccharide biosynthesis (wav) gene cluster.

    Science.gov (United States)

    Nesper, Jutta; Kraiss, Anita; Schild, Stefan; Blass, Julia; Klose, Karl E; Bockemühl, Jochen; Reidl, Joachim

    2002-05-01

    We identified five different putative wav gene cluster types, which are responsible for the synthesis of the core oligosaccharide (OS) region of Vibrio cholerae lipopolysaccharide. Preliminary evidence that the genes encoded by this cluster are involved in core OS biosynthesis came from analysis of the recently released O1 El Tor V. cholerae genome sequence and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of O1 El Tor mutant strains defective in three genes (waaF, waaL, and wavB). Investigations of 38 different V. cholerae strains by Southern blotting, PCR, and sequencing analyses showed that the O1 El Tor wav gene cluster type is prevalent among clinical isolates of different serogroups associated with cholera and environmental O1 strains. In contrast, we found differences in the wav gene contents of 19 unrelated non-O1, non-O139 environmental and human isolates not associated with cholera. These strains contained four new wav gene cluster types that differ from each other in distinct gene loci, providing evidence for horizontal transfer of wav genes and for limited structural diversity of the core OS among V. cholerae isolates. Our results show genetic diversity in the core OS biosynthesis gene cluster and predominance of the type 1 wav gene locus in strains associated with clinical cholera, suggesting that a specific core OS structure could contribute to V. cholerae virulence.

  11. Sleeping Beauty Mouse Models Identify Candidate Genes Involved in Gliomagenesis

    Science.gov (United States)

    Vyazunova, Irina; Maklakova, Vilena I.; Berman, Samuel; De, Ishani; Steffen, Megan D.; Hong, Won; Lincoln, Hayley; Morrissy, A. Sorana; Taylor, Michael D.; Akagi, Keiko; Brennan, Cameron W.; Rodriguez, Fausto J.; Collier, Lara S.

    2014-01-01

    Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma. PMID:25423036

  12. A multistep bioinformatic approach detects putative regulatory elements in gene promoters

    Directory of Open Access Journals (Sweden)

    Pizzi Cinzia

    2005-05-01

    Full Text Available Abstract Background Searching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for definition of a sheltered search space and of appropriate search parameters, in order to develop a method for identification of a tractable number of sequence motifs. Results Novel software (COOP was developed for extraction of sequence motifs, based on clustering of exact or approximate patterns according to the frequency of their overlapping occurrences. Genomic sequences of 1 Kb upstream of 91 genes differentially expressed and/or encoding proteins with relevant function in adult human retina were analyzed. Methodology and results were tested by analysing 1,000 groups of putatively unrelated sequences, randomly selected among 17,156 human gene promoters. When applied to a sample of human promoters, the method identified 279 putative motifs frequently occurring in retina promoters sequences. Most of them are localized in the proximal portion of promoters, less variable in central region than in lateral regions and similar to known regulatory sequences. COOP software and reference manual are freely available upon request to the Authors. Conclusion The approach described in this paper seems effective for identifying a tractable number of sequence motifs with putative regulatory role.

  13. A multistep bioinformatic approach detects putative regulatory elements in gene promoters

    Science.gov (United States)

    Bortoluzzi, Stefania; Coppe, Alessandro; Bisognin, Andrea; Pizzi, Cinzia; Danieli, Gian Antonio

    2005-01-01

    Background Searching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for definition of a sheltered search space and of appropriate search parameters, in order to develop a method for identification of a tractable number of sequence motifs. Results Novel software (COOP) was developed for extraction of sequence motifs, based on clustering of exact or approximate patterns according to the frequency of their overlapping occurrences. Genomic sequences of 1 Kb upstream of 91 genes differentially expressed and/or encoding proteins with relevant function in adult human retina were analyzed. Methodology and results were tested by analysing 1,000 groups of putatively unrelated sequences, randomly selected among 17,156 human gene promoters. When applied to a sample of human promoters, the method identified 279 putative motifs frequently occurring in retina promoters sequences. Most of them are localized in the proximal portion of promoters, less variable in central region than in lateral regions and similar to known regulatory sequences. COOP software and reference manual are freely available upon request to the Authors. Conclusion The approach described in this paper seems effective for identifying a tractable number of sequence motifs with putative regulatory role. PMID:15904489

  14. Classification of genes and putative biomarker identification using distribution metrics on expression profiles.

    Directory of Open Access Journals (Sweden)

    Hung-Chung Huang

    Full Text Available BACKGROUND: Identification of genes with switch-like properties will facilitate discovery of regulatory mechanisms that underlie these properties, and will provide knowledge for the appropriate application of Boolean networks in gene regulatory models. As switch-like behavior is likely associated with tissue-specific expression, these gene products are expected to be plausible candidates as tissue-specific biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: In a systematic classification of genes and search for biomarkers, gene expression profiles (GEPs of more than 16,000 genes from 2,145 mouse array samples were analyzed. Four distribution metrics (mean, standard deviation, kurtosis and skewness were used to classify GEPs into four categories: predominantly-off, predominantly-on, graded (rheostatic, and switch-like genes. The arrays under study were also grouped and examined by tissue type. For example, arrays were categorized as 'brain group' and 'non-brain group'; the Kolmogorov-Smirnov distance and Pearson correlation coefficient were then used to compare GEPs between brain and non-brain for each gene. We were thus able to identify tissue-specific biomarker candidate genes. CONCLUSIONS/SIGNIFICANCE: The methodology employed here may be used to facilitate disease-specific biomarker discovery.

  15. Conserved co-expression for candidate disease gene prioritization

    Directory of Open Access Journals (Sweden)

    Huynen Martijn A

    2008-04-01

    Full Text Available Abstract Background Genes that are co-expressed tend to be involved in the same biological process. However, co-expression is not a very reliable predictor of functional links between genes. The evolutionary conservation of co-expression between species can be used to predict protein function more reliably than co-expression in a single species. Here we examine whether co-expression across multiple species is also a better prioritizer of disease genes than is co-expression between human genes alone. Results We use co-expression data from yeast (S. cerevisiae, nematode worm (C. elegans, fruit fly (D. melanogaster, mouse and human and find that the use of evolutionary conservation can indeed improve the predictive value of co-expression. The effect that genes causing the same disease have higher co-expression than do other genes from their associated disease loci, is significantly enhanced when co-expression data are combined across evolutionarily distant species. We also find that performance can vary significantly depending on the co-expression datasets used, and just using more data does not necessarily lead to better prioritization. Instead, we find that dataset quality is more important than quantity, and using a consistent microarray platform per species leads to better performance than using more inclusive datasets pooled from various platforms. Conclusion We find that evolutionarily conserved gene co-expression prioritizes disease candidate genes better than human gene co-expression alone, and provide the integrated data as a new resource for disease gene prioritization tools.

  16. Adaptations to climate in candidate genes for common metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Angela M Hancock

    2008-02-01

    Full Text Available Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.

  17. Identification and functional analysis of Penicillium digitatum genes putatively involved in virulence towards citrus fruit.

    Science.gov (United States)

    López-Pérez, Mario; Ballester, Ana-Rosa; González-Candelas, Luis

    2015-04-01

    The fungus Penicillium digitatum, the causal agent of green mould rot, is the most destructive post-harvest pathogen of citrus fruit in Mediterranean regions. In order to identify P. digitatum genes up-regulated during the infection of oranges that may constitute putative virulence factors, we followed a polymerase chain reaction (PCR)-based suppression subtractive hybridization and cDNA macroarray hybridization approach. The origin of expressed sequence tags (ESTs) was determined by comparison against the available genome sequences of both organisms. Genes coding for fungal proteases and plant cell wall-degrading enzymes represent the largest categories in the subtracted cDNA library. Northern blot analysis of a selection of P. digitatum genes, including those coding for proteases, cell wall-related enzymes, redox homoeostasis and detoxification processes, confirmed their up-regulation at varying time points during the infection process. Agrobacterium tumefaciens-mediated transformation was used to generate knockout mutants for two genes encoding a pectin lyase (Pnl1) and a naphthalene dioxygenase (Ndo1). Two independent P. digitatum Δndo1 mutants were as virulent as the wild-type. However, the two Δpnl1 mutants analysed were less virulent than the parental strain or an ectopic transformant. Together, these results provide a significant advance in our understanding of the putative determinants of the virulence mechanisms of P. digitatum. PMID:25099378

  18. Identification and functional analysis of Penicillium digitatum genes putatively involved in virulence towards citrus fruit.

    Science.gov (United States)

    López-Pérez, Mario; Ballester, Ana-Rosa; González-Candelas, Luis

    2015-04-01

    The fungus Penicillium digitatum, the causal agent of green mould rot, is the most destructive post-harvest pathogen of citrus fruit in Mediterranean regions. In order to identify P. digitatum genes up-regulated during the infection of oranges that may constitute putative virulence factors, we followed a polymerase chain reaction (PCR)-based suppression subtractive hybridization and cDNA macroarray hybridization approach. The origin of expressed sequence tags (ESTs) was determined by comparison against the available genome sequences of both organisms. Genes coding for fungal proteases and plant cell wall-degrading enzymes represent the largest categories in the subtracted cDNA library. Northern blot analysis of a selection of P. digitatum genes, including those coding for proteases, cell wall-related enzymes, redox homoeostasis and detoxification processes, confirmed their up-regulation at varying time points during the infection process. Agrobacterium tumefaciens-mediated transformation was used to generate knockout mutants for two genes encoding a pectin lyase (Pnl1) and a naphthalene dioxygenase (Ndo1). Two independent P. digitatum Δndo1 mutants were as virulent as the wild-type. However, the two Δpnl1 mutants analysed were less virulent than the parental strain or an ectopic transformant. Together, these results provide a significant advance in our understanding of the putative determinants of the virulence mechanisms of P. digitatum.

  19. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

    Directory of Open Access Journals (Sweden)

    Junhua Li

    2014-01-01

    Full Text Available Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

  20. Digital transcriptome analysis of putative sex-determination genes in papaya (Carica papaya.

    Directory of Open Access Journals (Sweden)

    Naoya Urasaki

    Full Text Available Papaya (Carica papaya is a trioecious plant species that has male, female and hermaphrodite flowers on different plants. The primitive sex chromosomes genetically determine the sex of the papaya. Although draft sequences of the papaya genome are already available, the genes for sex determination have not been identified, likely due to the complicated structure of its sex-chromosome sequences. To identify the candidate genes for sex determination, we conducted a transcriptome analysis of flower samples from male, female and hermaphrodite plants using high-throughput SuperSAGE for digital gene expression analysis. Among the short sequence tags obtained from the transcripts, 312 unique tags were specifically mapped to the primitive sex chromosome (X or Y(h sequences. An annotation analysis revealed that retroelements are the most abundant sequences observed in the genes corresponding to these tags. The majority of tags on the sex chromosomes were located on the X chromosome, and only 30 tags were commonly mapped to both the X and Y(h chromosome, implying a loss of many genes on the Y(h chromosome. Nevertheless, candidate Y(h chromosome-specific female determination genes, including a MADS-box gene, were identified. Information on these sex chromosome-specific expressed genes will help elucidating sex determination in the papaya.

  1. Digital transcriptome analysis of putative sex-determination genes in papaya (Carica papaya).

    Science.gov (United States)

    Urasaki, Naoya; Tarora, Kazuhiko; Shudo, Ayano; Ueno, Hiroki; Tamaki, Moritoshi; Miyagi, Norimichi; Adaniya, Shinichi; Matsumura, Hideo

    2012-01-01

    Papaya (Carica papaya) is a trioecious plant species that has male, female and hermaphrodite flowers on different plants. The primitive sex chromosomes genetically determine the sex of the papaya. Although draft sequences of the papaya genome are already available, the genes for sex determination have not been identified, likely due to the complicated structure of its sex-chromosome sequences. To identify the candidate genes for sex determination, we conducted a transcriptome analysis of flower samples from male, female and hermaphrodite plants using high-throughput SuperSAGE for digital gene expression analysis. Among the short sequence tags obtained from the transcripts, 312 unique tags were specifically mapped to the primitive sex chromosome (X or Y(h)) sequences. An annotation analysis revealed that retroelements are the most abundant sequences observed in the genes corresponding to these tags. The majority of tags on the sex chromosomes were located on the X chromosome, and only 30 tags were commonly mapped to both the X and Y(h) chromosome, implying a loss of many genes on the Y(h) chromosome. Nevertheless, candidate Y(h) chromosome-specific female determination genes, including a MADS-box gene, were identified. Information on these sex chromosome-specific expressed genes will help elucidating sex determination in the papaya.

  2. A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy

    DEFF Research Database (Denmark)

    Bruhn, Sören; Fang, Yu; Barrenäs, Fredrik;

    2014-01-01

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identi...

  3. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Directory of Open Access Journals (Sweden)

    Giovannetti Marco

    2012-10-01

    Full Text Available Abstract Background Arbuscular mycorrhizas (AM are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis.

  4. Candidate Genes Involved in the Biosynthesis of Triterpenoid Saponins in Platycodon grandiflorum Identified by Transcriptome Analysis

    Science.gov (United States)

    Ma, Chun-Hua; Gao, Zheng-Jie; Zhang, Jia-Jin; Zhang, Wei; Shao, Jian-Hui; Hai, Mei-Rong; Chen, Jun-Wen; Yang, Sheng-Chao; Zhang, Guang-Hui

    2016-01-01

    Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese, and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable. Principal findings: A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80%) were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG, and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant. Conclusion: The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level. PMID:27242873

  5. Candidate genes involved in the biosynthesis of triterpenoid saponins in Platycodon grandiflorum identified by transcriptome analysis

    Directory of Open Access Journals (Sweden)

    Chunhua eMa

    2016-05-01

    Full Text Available Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable.Principal Findings:A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80% were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant.Conclusion:The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level.

  6. Mutation analysis of novel human liver-related putative tumor suppressor gene in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Liao; Tsai-Ping Li; Mu-Jun Zhao; Jing Zhao; Hai Song; Pascal Pineau; Agnès Marchio; Anne Dejean; Pierre Tiollais; Hong-Yang Wang

    2003-01-01

    AIM: To find the point mutations meaningful for inactivationof liver-related putative tumor suppressor gene (LPTS) gene,a human novel liver-related putative tumor suppressor geneand telomerase inhibitor in hepatocellular carcinoma.METHODS: The entire coding sequence of LPTS genewas examined for mutations by single strand conformationpolymorphism (SSCP) assay and PCR products directsequencing in 56 liver cancer cell lines, 7 ovarian cancerand 7 head & neck tumor cell lines and 70 pairs of HCCtissues samples. The cDNA fragment coding for the mostfrequent mutant protein was subcloned into GST fusionexpression vector. The product was expressed in E. coliand purified by glutathione-agarose column. Telomericrepeat amplification protocol (TRAP) assays wereperformed to study the effect of point mutation totelomerase inhibitory activity.RESULTS: SSCP gels showed the abnormal shifting bandsand DNA sequencing found that there were 5 differentmutations and/or polymorphisms in 12 tumor cell lineslocated at exon2, exon5 and exon7. The main alterationswere A(778)A/G and A(880)T in exon7. The change in siteof 778 could not be found in HCC tissue samples, while themutation in position 880 was seen in 7 (10 %) cases. Themutation in the site of 880 had no effect on telomeraseinhibitory activity.CONCLUSION: Alterations identified in this study arepolymorphisms of LPTS gene. LPTS mutations occur in HCCbut are infrequent and of little effect on the telomeraseinhibitory function of the protein. Epigenetics, such asmethylation, acetylation, may play the key role in inactivationof LPTS.

  7. Eliminated chromatin of Ascaris contains a gene that encodes a putative ribosomal protein.

    OpenAIRE

    Etter, A; Aboutanos, M; Tobler, H; Müller, F.

    1991-01-01

    Chromatin diminution in the nematodes Parascaris equorum and Ascaris lumbricoides leads to the formation of somatic cells that contain less DNA than the germ-line cells. We present molecular evidence for the coding potential of germ-line-specific DNA. We report on a cDNA clone that codes for a putative ribosomal protein (ALEP-1, for A. lumbricoides eliminated protein 1). That the corresponding gene is located in the eliminated portion of the genome indicates a difference in germ-line and soma...

  8. Mammalian mitochondrial ribosomal small subunit (MRPS) genes: A putative role in human disease.

    Science.gov (United States)

    Gopisetty, Gopal; Thangarajan, Rajkumar

    2016-09-01

    Mitochondria are prominently understood as power houses producing ATP the primary energy currency of the cell. However, mitochondria are also known to play an important role in apoptosis and autophagy, and mitochondrial dysregulation can lead to pathological outcomes. Mitochondria are known to contain 1500 proteins of which only 13 are coded by mitochondrial DNA and the rest are coded by nuclear genes. Protein synthesis in mitochondria involves mitochondrial ribosomes which are 55-60S particles and are composed of small 28S and large 39S subunits. A feature of mammalian mitoribosome which differentiate it from bacterial ribosomes is the increased protein content. The human mitochondrial ribosomal protein (MRP) gene family comprises of 30 genes which code for mitochondrial ribosomal small subunit and 50 genes for the large subunit. The present review focuses on the mitochondrial ribosomal small subunit genes (MRPS), presents an overview of the literature and data gleaned from publicly available gene and protein expression databases. The survey revealed aberrations in MRPS gene expression patterns in varied human diseases indicating a putative role in their etiology. PMID:27170550

  9. Computational disease gene identification : a concert of methods prioritizes type 2 diabetes and obesity candidate genes

    NARCIS (Netherlands)

    Tiffin, N.; Adie, E.; Turner, F.; Brunner, H.G.; Driel, M.A. van; Oti, M.O.; Lopez-Bigas, N.; Ouzounis, C.A.; Perez-Iratxeta, C.; Andrade-Navarro, M.A.; Adeyemo, A.; Patti, M.E.; Semple, C.A.; Hide, W.

    2006-01-01

    Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most li

  10. Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes.

    NARCIS (Netherlands)

    Tiffin, N.; Adie, E.; Turner, F.; Brunner, H.G.; Driel, M.A. van; Oti, M.O.; Lopez-Bigas, N.; Ouzounis, C.A.; Perez-Iratxeta, C.; Andrade-Navarro, M.A.; Adeyemo, A.; Patti, M.E.; Semple, C.A.; Hide, W.

    2006-01-01

    Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most li

  11. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Eneour Puill-Stephan

    Full Text Available BACKGROUND: Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. METHODOLOGY/PRINCIPAL FINDINGS: Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR. Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria during winnowing processes as symbioses are fine-tuned. CONCLUSIONS/SIGNIFICANCE: Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies

  12. Syndrome to gene (S2G): in-silico identification of candidate genes for human diseases.

    Science.gov (United States)

    Gefen, Avitan; Cohen, Raphael; Birk, Ohad S

    2010-03-01

    The identification of genomic loci associated with human genetic syndromes has been significantly facilitated through the generation of high density SNP arrays. However, optimal selection of candidate genes from within such loci is still a tedious labor-intensive bottleneck. Syndrome to Gene (S2G) is based on novel algorithms which allow an efficient search for candidate genes in a genomic locus, using known genes whose defects cause phenotypically similar syndromes. S2G (http://fohs.bgu.ac.il/s2g/index.html) includes two components: a phenotype Online Mendelian Inheritance in Man (OMIM)-based search engine that alleviates many of the problems in the existing OMIM search engine (negation phrases, overlapping terms, etc.). The second component is a gene prioritizing engine that uses a novel algorithm to integrate information from 18 databases. When the detailed phenotype of a syndrome is inserted to the web-based software, S2G offers a complete improved search of the OMIM database for similar syndromes. The software then prioritizes a list of genes from within a genomic locus, based on their association with genes whose defects are known to underlie similar clinical syndromes. We demonstrate that in all 30 cases of novel disease genes identified in the past year, the disease gene was within the top 20% of candidate genes predicted by S2G, and in most cases--within the top 10%. Thus, S2G provides clinicians with an efficient tool for diagnosis and researchers with a candidate gene prediction tool based on phenotypic data and a wide range of gene data resources. S2G can also serve in studies of polygenic diseases, and in finding interacting molecules for any gene of choice.

  13. Investigation of two candidate genes for Hailey-Hailey disease

    Energy Technology Data Exchange (ETDEWEB)

    Peluso, A.M.; Ikeda, S.; Bonifas, J.M. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant skin disease characterized by impaired keratinocyte cohesion and consequent blister formation. Recently we have used linkage to map the gene for this disease to a region of chromosome 3q between D3S1589 and D3S1316. The maximum combined two point lod score in four families studied was 14.60 at {theta} = 0 at the D3S1290 microsatellite repeat. Several genes have been mapped to chromosome 3q21-24, including cellular retinol binding protein (RBP1) and rhodopsin (RHO). Using microsatellite repeat for RHO we have found a recombinant with the RHO gene and Hailey-Hailey disease in one patient. Because of the profound effects of retinoids on epidermal differentiation, RBP1 could be considered as a possible candidate gene. We have amplified genomic DNA from patients from 14 individual families with Hailey-Hailey disease and 10 different control samples for each of the 4 exons of RBP1. Thus far, SSCP analysis has failed to detect different banding patterns in patients versus controls. We are now attempting to extend this RBP1 analysis and are collecting new families to use linkage analysis to narrow this still rather large (approximately 14 cM) interval.

  14. Candidate gene analysis of osteochondrosis in Spanish Purebred horses.

    Science.gov (United States)

    Sevane, N; Dunner, S; Boado, A; Cañon, J

    2016-10-01

    Equine osteochondrosis (OC) is a frequent developmental orthopaedic disease with high economic impact on the equine industry and may lead to premature retirement of the animal as a result of chronic pain and lameness. The genetic background of OC includes different genes affecting several locations; however, these genetic associations have been tested in only one or few populations, lacking the validation in others. The aim of this study was to identify the genetic determinants of OC in the Spanish Purebred horse breed. For that purpose, we used a candidate gene approach to study the association between loci previously implicated in the onset and development of OC in other breeds and different OC locations using radiographic data from 144 individuals belonging to the Spanish Purebred horse breed. Of the 48 polymorphisms analysed, three single nucleotide polymorphisms (SNPs) located in the FAF1, FCN3 and COL1A2 genes were found to be associated with different locations of OC lesions. These data contribute insights into the complex gene networks underlying the multifactorial disease OC, and the associated SNPs could be used in a marker-assisted selection strategy to improve horse health, welfare and competitive lifespan. PMID:27422688

  15. Novel primary immunodeficiency candidate genes predicted by the human gene connectome

    Directory of Open Access Journals (Sweden)

    Yuval eItan

    2015-04-01

    Full Text Available Germline genetic mutations underlie various primary immunodeficiency (PID diseases. Patients with rare PID diseases (like most non-PID patients and healthy individuals carry, on average, 20,000 rare and common coding variants detected by high throughput sequencing. It is thus a major challenge to select only a few candidate disease-causing variants for experimental testing. One of the tools commonly used in the pipeline for estimating a potential PID candidate gene is to test whether the specific gene is included in the list of genes that were already experimentally validated as PID-causing in previous studies. However, this approach is limited because it cannot detect the PID-causing mutation(s in the many PID patients carrying causal mutations of as yet unidentified PID-causing genes. In this study, we expanded in silico the list of potential PID-causing candidate genes from 229 to 3,110. We first identified the top 1% of human genes predicted by the human genes connectome to be biologically close to the 229 known PID genes. We then further narrowed down the list of genes by retaining only the most biologically relevant genes, with functionally enriched gene ontology biological categories similar to those for the known PID genes. We validated this prediction by showing that 17 of the 21 novel PID genes published since the last IUIS classification fall into this group of 3,110 genes (p<10-7. The resulting new extended list of 3,110 predicted PID genes should be useful for the discovery of novel PID genes in patients.

  16. Identifying disease candidate genes via large-scale gene network analysis.

    Science.gov (United States)

    Kim, Haseong; Park, Taesung; Gelenbe, Erol

    2014-01-01

    Gene Regulatory Networks (GRN) provide systematic views of complex living systems, offering reliable and large-scale GRNs to identify disease candidate genes. A reverse engineering technique, Bayesian Model Averaging-based Networks (BMAnet), which ensembles all appropriate linear models to tackle uncertainty in model selection that integrates heterogeneous biological data sets is introduced. Using network evaluation metrics, we compare the networks that are thus identified. The metric 'Random walk with restart (Rwr)' is utilised to search for disease genes. In a simulation our method shows better performance than elastic-net and Gaussian graphical models, but topological quantities vary among the three methods. Using real-data, brain tumour gene expression samples consisting of non-tumour, grade III and grade IV are analysed to estimate networks with a total of 4422 genes. Based on these networks, 169 brain tumour-related candidate genes were identified and some were found to relate to 'wound', 'apoptosis', and 'cell death' processes. PMID:25796737

  17. Combining quantitative trait loci and heterogeneous microarray data analyses reveals putative candidate pathways affecting mastitis in cattle.

    Science.gov (United States)

    Lewandowska-Sabat, A M; Günther, J; Seyfert, H M; Olsaker, I

    2012-12-01

    Mastitis is a frequent disease and considerable problem for the global dairy industry. Identification of solutions leading to the development of new control strategies is therefore of high importance. In this study, we have integrated genomic data from genome-wide association mapping in cattle with transcriptomic data from microarray studies of several mastitis pathogens and host species in vitro and in vivo. To identify significant candidate pathways directly and indirectly involved in the immune response to mastitis, ingenuity pathway analysis (ipa) and database for annotation, visualization and integrated discovery bioinformatic (david) were applied. Several candidate pathways were found. Of great interest are IL-17 and IL-8 signalling pathways, responsible for the recruitment and migration of inflammatory cells into tissue during inflammation and infection. These results may emphasize further functional studies for identification of factors contributing to resistance to mastitis pathogens in cattle.

  18. Identification of Candidate Genes Associated with Beef Marbling Using QTL and Pathway Analysis in Hanwoo (Korean Cattle)

    OpenAIRE

    Park, Hyesun; Seo, Seongwon; Cho, Yong Min; Oh, Sung Jong; Seong, Hwan-Hoo; Lee, Seung Hwan; Lim, Dajeong

    2012-01-01

    Marbling from intramuscular fat is an important trait of meat quality and has an economic benefit for the beef industry. Quantitative trait loci (QTL) fine mapping was performed to identify the marbling trait in 266 Hanwoo steers using a 10K single nucleotide polymorphism panel with the combined linkage and linkage disequilibrium method. As a result, we found nine putative QTL regions for marbling: three on BTA6, two on BTA17, two on BTA22, and two on BTA29. We detected candidate genes for ma...

  19. Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze).

    Science.gov (United States)

    Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar

    2016-01-01

    To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops. PMID:27465480

  20. Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze)

    Science.gov (United States)

    Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar

    2016-07-01

    To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.

  1. Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes

    Directory of Open Access Journals (Sweden)

    Rowe J

    2009-08-01

    Full Text Available Abstract Background Guanine-rich nucleic acid sequences are capable of folding into an intramolecular four-stranded structure called a G-quadruplex. When found in gene promoter regions, G-quadruplexes can downregulate gene expression, possibly by blocking the transcriptional machinery. Here we have used a genome-wide bioinformatic approach to identify Putative G-Quadruplex Sequences (PQS in the Plasmodium falciparum genome, along with biophysical techniques to examine the physiological stability of P. falciparum PQS in vitro. Results We identified 63 PQS in the non-telomeric regions of the P. falciparum clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the P. falciparum var genes (group B var genes. The var gene family encodes PfEMP1, the parasite's major variant antigen and adhesin expressed at the surface of infected erythrocytes, that plays a key role in malaria pathogenesis and immune evasion. The ability of the PQS found in the upstream regions of group B var genes (UpsB-Q to form stable G-quadruplex structures in vitro was confirmed using 1H NMR, circular dichroism, UV spectroscopy, and thermal denaturation experiments. Moreover, the synthetic compound BOQ1 that shows a higher affinity for DNA forming quadruplex rather than duplex structures was found to bind with high affinity to the UpsB-Q. Conclusion This is the first demonstration of non-telomeric PQS in the genome of P. falciparum that form stable G-quadruplexes under physiological conditions in vitro. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of var genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family.

  2. Genetics of intracerebral hemorrhage: Insights from candidate gene approaches

    Directory of Open Access Journals (Sweden)

    Baoqiong Liu

    2012-01-01

    Full Text Available Intracerebral hemorrhage (ICH is a heterogeneous disease with genetic factors playing an important role. Association studies on a wide range of candidate pathways suggest a weak but significant effect for several alleles with ICH risk. Among the most widely investigated genes are those involved in the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme, coagulation pathway (e.g., Factor XIII, Factor VII, platelet-activating factor acetylhydrolase, Factor V Leiden, and beta1-tubulin, lipid metabolism (e.g., apolipoproteins (ApoE, Apo(a, ApoH, homocysteine metabolism (e.g., methylenetetrahydrofolate reductase, inflammation (e.g., interleukin-6 and tumor necrosis-alpha and other candidate pathways. To identify the robustness of the above associations with ICH, a search of Pubmed (1988 through December 2011 was performed, with searches limited to English-language studies conducted among adult human subjects. This article presents a review of the examined literature on the genetics of ICH.

  3. Isolation of a rice gene homologous to the human putative tumor suppressor gene QM

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    QM gene was originally isolated from human by Dowdy et al during a search for a wilms′ tumor suppressor gene. Researches of QM gene focused mainly on animals and yeasts, little was known about plant QM gene. For better understanding of QM gene in rice, a QM homologous fragment was used as a probe to screen rice (Oryza sativa subsp. indica c.v. Guanglu′ ai 4) genomic DNA library,and two clones were obtained. One of them, OSQM2, encoded a highly basic protein of 184 amino acids, the sequence was about 3.1 kb long with a very special promoter region compared with other known QM genes. Seven potential G boxes could be found between -690 and -230. G box, which contains a ACGT core motif, had been reported in many plants to act as a cis acting DNA element in the regulation of genes in a variety of environmental conditions, such as ABA regulated gene expression, red light, UV light, anaerobiosis, and wounding etc. Two closely linked DRE related motifs (dehydration responsive element) could also be found between -182 and 173, which had a CCGAC conserved sequence and had been identified in many cold and drought responsive genes in Arabidopsis. Six MYC recognition sequences with the conserved motif NCANNTGN were also presented, which might be essential for ABA and drought responsive expression of the plant genes.

  4. Complete Genome Sequence of the Filamentous Fungus Aspergillus westerdijkiae Reveals the Putative Biosynthetic Gene Cluster of Ochratoxin A.

    Science.gov (United States)

    Chakrabortti, Alolika; Li, Jinming; Liang, Zhao-Xun

    2016-01-01

    Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae, a major producer of OTA, reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins. PMID:27635003

  5. Complete Genome Sequence of the Filamentous Fungus Aspergillus westerdijkiae Reveals the Putative Biosynthetic Gene Cluster of Ochratoxin A

    Science.gov (United States)

    Chakrabortti, Alolika; Li, Jinming

    2016-01-01

    Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae, a major producer of OTA, reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins. PMID:27635003

  6. Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer.

    Science.gov (United States)

    Mercier, Pierre-Luc; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Ghani, Karim; Têtu, Bernard; Bairati, Isabelle; Bachvarov, Dimcho

    2011-10-01

    In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest was DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5'-non-coding DNA region (located at nt -1158 to -850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the contrary, DOK1 was found to be strongly overexpressed in serous EOC tumors as compared to normal tissue and importantly, DOK1 overexpression significantly correlated with improved progression-free survival (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC cells and consecutive functional analyses pointed toward association of DOK1 expression with increased EOC cell migration and proliferation, and better sensitivity to cisplatin treatment. Gene expression profiling and consecutive network and pathway analyses were also confirmative for DOK1 association with EOC cell migration and proliferation. These analyses were also indicative for DOK1 protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some tumor suppressor factors and its suppression of pro-metastasis genes. Taken together, our findings are suggestive for a possible tumor suppressor role of DOK1 in EOC; however its implication in enhanced EOC cell migration and proliferation restrain us to conclude that DOK1 represents a true TSG in EOC. Further studies are needed to more completely elucidate the functional implications of DOK1 and other members of the DOK gene family in ovarian

  7. A candidate gene for X-linked Ocular Albinism (OA1)

    Energy Technology Data Exchange (ETDEWEB)

    Bassi, M.T.; Schiaffino, V.; Rugarli, E. [Baylor College of Medicine, Houston, TX (United States)

    1994-09-01

    Ocular Albinism of the Nettleship-Fall type 1 (OA1) is the most common form of ocular albinism. It is transmitted as an X-linked recessive trait with affected males showing severe reduction of visual acuity, nystagmus, strabismus, photophobia. Ophthalmologic examination reveals foveal hypoplasia, hypopigmentation of the retina and iris translucency. Microscopic examination of melanocytes suggests that the underlying defect in OA1 is an abnormality in melanosome formation. Recently we assembled a 350 kb cosmid contig spanning the entire critical region on Xp22.3, which measures approximately 110 kb. A minimum set of cosmids was used to identify transcribed sequences using both cDNA selection and exon amplification. Two putative exons recovered by exon amplification strategy were found to be highly conserved throughout evolution and, therefore, they were used as probes for the screening of fetal and adult retina cDNA libraries. This led to the isolation of clones spanning a full-length cDNA which measures 7.6 kb. Sequence analysis revealed that the predicted protein product shows homology with syntrophines and a Xenopus laevis apical protein. The gene covers approximately 170 kb of DNA and spans the entire critical region for OA1, being deleted in two patients with contiguous gene deletion including OA1 and in one patient with isolated OA1. Therefore, this new gene represents a very strong candidate for involvement in OA1 (an alternative, but unlikely possibility to be considered is that the true OA1 gene lies within an intron of the former). Northern analysis revealed very high level of expression in retina and melanoma. Unlike most Xp22.3 genes, this gene is conserved in the mouse. We are currently performing SSCP analysis and direct sequencing of exons on DNAs from approximately 60 unrelated patients with OA1 for mutation detection.

  8. Flower Development and Perianth Identity Candidate Genes in the Basal Angiosperm Aristolochia fimbriata (Piperales: Aristolochiaceae)

    Science.gov (United States)

    Pabón-Mora, Natalia; Suárez-Baron, Harold; Ambrose, Barbara A.; González, Favio

    2015-01-01

    Aristolochia fimbriata (Aristolochiaceae: Piperales) exhibits highly synorganized flowers with a single convoluted structure forming a petaloid perianth that surrounds the gynostemium, putatively formed by the congenital fusion between stamens and the upper portion of the carpels. Here we present the flower development and morphology of A. fimbriata, together with the expression of the key regulatory genes that participate in flower development, particularly those likely controlling perianth identity. A. fimbriata is a member of the magnoliids, and thus gene expression detected for all ABCE MADS-box genes in this taxon, can also help to elucidate patterns of gene expression prior the independent duplications of these genes in eudicots and monocots. Using both floral development and anatomy in combination with the isolation of MADS-box gene homologs, gene phylogenetic analyses and expression studies (both by reverse transcription PCR and in situ hybridization), we present hypotheses on floral organ identity genes involved in the formation of this bizarre flower. We found that most MADS-box genes were expressed in vegetative and reproductive tissues with the exception of AfimSEP2, AfimAGL6, and AfimSTK transcripts that are only found in flowers and capsules but are not detected in leaves. Two genes show ubiquitous expression; AfimFUL that is found in all floral organs at all developmental stages as well as in leaves and capsules, and AfimAG that has low expression in leaves and is found in all floral organs at all stages with a considerable reduction of expression in the limb of anthetic flowers. Our results indicate that expression of AfimFUL is indicative of pleiotropic roles and not of a perianth identity specific function. On the other hand, expression of B-class genes, AfimAP3 and AfimPI, suggests their conserved role in stamen identity and corroborates that the perianth is sepal and not petal-derived. Our data also postulates an AGL6 ortholog as a candidate

  9. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis

    DEFF Research Database (Denmark)

    Grauers, Anna; Wang, Jingwen; Einarsdottir, Elisabet;

    2015-01-01

    that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding. PURPOSE: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study...... samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5'UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing......, were Sanger sequenced in the 100 pooled samples. RESULTS: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10(-18)). We identified 20 novel variants...

  10. Prevalence of ten putative virulence genes in the emerging foodborne pathogen Arcobacter isolated from food products.

    Science.gov (United States)

    Girbau, Cecilia; Guerra, Cristian; Martínez-Malaxetxebarria, Irati; Alonso, Rodrigo; Fernández-Astorga, Aurora

    2015-12-01

    Arcobacter spp. are considered to be emerging food- and waterborne pathogens for both humans and animals. However, their virulence mechanisms are still poorly understood. In this study the presence of ten virulence genes (cadF, ciaB, cj1349, hecA, hecB, mviN, pldA, irgA, tlyA and iroE) was assessed in a set of 47 strains of Arcobacter butzleri, 10 of Arcobacter cryaerophilus and 1 Arcobacter skirrowii strain recovered from different food products (pork, chicken, beef, milk, clams and mussels). Overall, the genes cadF, ciaB, cj1349, mviN, pldA and tlyA were detected in all A. butzleri and A. skirrowii strains. Lower detection rates were observed for irgA, iroE, hecA and hecB. The genes hecB and iroE were detected neither in A. cryaerophilus nor in A. skirrowii. The genes hecA and irgA were not detected in A. skirrowii. It was noteworthy that the genes hecA and hecB were significantly (P < 0.05) highly detected in A. butzleri strains isolated from clams compared with strains isolated from milk and chicken. Therefore, our findings underline clams as a source of A. butzleri strains with high prevalence of putative virulence genes. This could be hazardous to human health, especially because these bivalves are usually consumed raw or undercooked.

  11. Association of single nucleotide polymorphisms in candidate genes residing under quantitative trait loci in beef cattle

    Science.gov (United States)

    The objective was to assess the association of single nucleotide polymorphisms (SNP) developed on candidate genes residing under previously identified quantitative trait loci for marbling score and meat tenderness. Two hundred five SNP were identified on twenty candidate genes. Genes selected under ...

  12. Association of twelve candidate gene polymorphisms and response to challenge with Salmonella enteritidis in poultry

    NARCIS (Netherlands)

    Kramer, J.; Malek, M.; Lamont, S.J.

    2003-01-01

    Breeding for disease resistance to Salmonella enteritidis (SE) could be an effective approach to control Salmonella in poultry. The candidate gene approach is a useful method to investigate genes that are involved in genetic resistance. In this study, 12 candidate genes that are involved in the path

  13. Functional Characterization of a Putative Nitrate Transporter Gene Promoter from Rice

    Institute of Scientific and Technical Information of China (English)

    Ting-Zhang HU; Kai-Ming CAO; Mian XIA; Xi-Ping WANG

    2006-01-01

    Drought is one of the most significant abiotic stresses that influence plant growth and development. Expression analysis revealed that OsNRT1.3, a putative nitrate transporter gene in rice, was induced by drought. To confirm if the OsNRT1.3 promoter can respond to drought stress, a 2019 bp upstream sequence of OsNRT1.3 was cloned. Three OsNRT1.3 promoter fragments were generated by 5'-deletion, and fused to the β-glucuronidase (GUS) gene. The chimeric genes were introduced into rice plants. NRT2019::GUS, NRT1196: :GUS and NRT719::GUS showed similar expression patterns in seeds,roots, leaves and flowers in all transgenic rice, and GUS activity conferred by different OsNRT1.3 promoter fragments was significantly upregulated by drought stress, indicating that OsNRT1.3 promoter responds to drought stress and the 719 bp upstream sequence of OsNRT1.3 contains the drought response elements.

  14. Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes.

    Science.gov (United States)

    Schriemer, Duco; Sribudiani, Yunia; IJpma, Arne; Natarajan, Dipa; MacKenzie, Katherine C; Metzger, Marco; Binder, Ellen; Burns, Alan J; Thapar, Nikhil; Hofstra, Robert M W; Eggen, Bart J L

    2016-08-01

    The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor A2a (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR. PMID:27266404

  15. Disruption of the Putative Vascular Leak Peptide Sequence in the Stabilized Ricin Vaccine Candidate RTA1-33/44-198

    Directory of Open Access Journals (Sweden)

    Charles B. Millard

    2013-01-01

    Full Text Available Vitetta and colleagues identified and characterized a putative vascular leak peptide (VLP consensus sequence in recombinant ricin toxin A-chain (RTA that contributed to dose-limiting human toxicity when RTA was administered intravenously in large quantities during chemotherapy. We disrupted this potentially toxic site within the more stable RTA1-33/44-198 vaccine immunogen and determined the impact of these mutations on protein stability, structure and protective immunogenicity using an experimental intranasal ricin challenge model in BALB/c mice to determine if the mutations were compatible. Single amino acid substitutions at the positions corresponding with RTA D75 (to A, or N and V76 (to I, or M had minor effects on the apparent protein melting temperature of RTA1-33/44-198 but all four variants retained greater apparent stability than the parent RTA. Moreover, each VLP(− variant tested provided protection comparable with that of RTA1-33/44-198 against supralethal intranasal ricin challenge as judged by animal survival and several biomarkers. To understand better how VLP substitutions and mutations near the VLP site impact epitope structure, we introduced a previously described thermal stabilizing disulfide bond (R48C/T77C along with the D75N or V76I substitutions in RTA1-33/44-198. The D75N mutation was compatible with the adjacent stabilizing R48C/T77C disulfide bond and the Tm was unaffected, whereas the V76I mutation was less compatible with the adjacent disulfide bond involving C77. A crystal structure of the RTA1-33/44-198 R48C/T77C/D75N variant showed that the structural integrity of the immunogen was largely conserved and that a stable immunogen could be produced from E. coli. We conclude that it is feasible to disrupt the VLP site in RTA1-33/44-198 with little or no impact on apparent protein stability or protective efficacy in mice and such variants can be stabilized further by introduction of a disulfide bond.

  16. Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive architecture in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Carla P. Coelho

    2014-05-01

    Full Text Available Agriculturally important grasses such as rice, maize and sugarcane are evolutionarily distant from Arabidopsis, yet some components of the floral induction process are highly conserved. Flowering in sugarcane is an important factor that negatively affects cane yield and reduces sugar/ethanol production from this important perennial bioenergy crop. Comparative studies have facilitated the identification and characterization of putative orthologs of key flowering time genes in sugarcane, a complex polyploid plant whose genome has yet to be sequenced completely. Using this approach we identified phosphatidylethanolamine-binding protein (PEBP gene family members in sugarcane that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play an essential role in controlling the transition from vegetative to reproductive growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral repressors, showed transcripts in developing leaves surrounding the shoot apex but not at the apex itself. ScFT1 was detected in immature leaves and apical regions of vegetatively growing plants and, after the floral transition, expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a gene related to TFL1. In addition, lines with the latest flowering phenotype exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which has greatest similarity to the florigen-encoding FT, also caused a delay in flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene family members from Saccharum spp. suggests that their expression patterns and roles in the floral transition has diverged from the predicted role of similar PEBP family members.

  17. Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive architecture in Arabidopsis

    Science.gov (United States)

    Coelho, Carla P.; Minow, Mark A. A.; Chalfun-Júnior, Antonio; Colasanti, Joseph

    2014-01-01

    Agriculturally important grasses such as rice, maize, and sugarcane are evolutionarily distant from Arabidopsis, yet some components of the floral induction process are highly conserved. Flowering in sugarcane is an important factor that negatively affects cane yield and reduces sugar/ethanol production from this important perennial bioenergy crop. Comparative studies have facilitated the identification and characterization of putative orthologs of key flowering time genes in sugarcane, a complex polyploid plant whose genome has yet to be sequenced completely. Using this approach we identified phosphatidylethanolamine-binding protein (PEBP) gene family members in sugarcane that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play an essential role in controlling the transition from vegetative to reproductive growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral repressors, showed transcripts in developing leaves surrounding the shoot apex but not at the apex itself. ScFT1 was detected in immature leaves and apical regions of vegetatively growing plants and, after the floral transition, expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a gene related to TFL1. In addition, lines with the latest flowering phenotype exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which has greatest similarity to the florigen-encoding FT, also caused a delay in flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene family members from Saccharum spp. suggests that their expression patterns and roles in the floral transition has diverged from the predicted role of similar PEBP family members. PMID:24904616

  18. Analysis of dyslexia candidate genes in the Raine cohort representing the general Australian population

    OpenAIRE

    Paracchini, S; Ang, Q W; Stanley, F J; Monaco, A. P.; Pennell, C E; Whitehouse, A J O

    2011-01-01

    Several genes have been suggested as dyslexia candidates. Some of these candidate genes have been recently shown to be associated with literacy measures in sample cohorts derived from the general population. Here, we have conducted an association study in a novel sample derived from the Australian population (the Raine cohort) to further investigate the role of dyslexia candidate genes. We analysed markers, previously reported to be associated with dyslexia, located within the MRPL19/C2ORF3, ...

  19. A candidate gene association study for growth performance in an improved giant freshwater prawn (Macrobrachium rosenbergii ) culture line.

    Science.gov (United States)

    Jung, Hyungtaek; Lyons, Russell E; Li, Yutao; Thanh, Nguyen Minh; Dinh, Hung; Hurwood, David A; Salin, Krishna R; Mather, Peter B

    2014-04-01

    A candidate gene approach using type I single nucleotide polymorphism (SNP) markers can provide an effective method for detecting genes and gene regions that underlie phenotypic variation in adaptively significant traits. In the absence of available genomic data resources, transcriptomes were recently generated in Macrobrachium rosenbergii to identify candidate genes and markers potentially associated with growth. The characterisation of 47 candidate loci by ABI re-sequencing of four cultured and eight wild samples revealed 342 putative SNPs. Among these, 28 SNPs were selected in 23 growth-related candidate genes to genotype in 200 animals selected for improved growth performance in an experimental GFP culture line in Vietnam. The associations between SNP markers and individual growth performance were then examined. For additive and dominant effects, a total of three exonic SNPs in glycogen phosphorylase (additive), heat shock protein 90 (additive and dominant) and peroxidasin (additive), and a total of six intronic SNPs in ankyrin repeats-like protein (additive and dominant), rolling pebbles (dominant), transforming growth factor-β induced precursor (dominant), and UTP-glucose-1-phosphate uridylyltransferase 2 (dominant) genes showed significant associations with the estimated breeding values in the experimental animals (P =0.001-0.031). Individually, they explained 2.6-4.8 % of the genetic variance (R²=0.026-0.048). This is the first large set of SNP markers reported for M. rosenbergii and will be useful for confirmation of associations in other samples or culture lines as well as having applications in marker-assisted selection in future breeding programs.

  20. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease.

    Science.gov (United States)

    Ward, Lucas D; Kellis, Manolis

    2016-01-01

    More than 90% of common variants associated with complex traits do not affect proteins directly, but instead the circuits that control gene expression. This has increased the urgency of understanding the regulatory genome as a key component for translating genetic results into mechanistic insights and ultimately therapeutics. To address this challenge, we developed HaploReg (http://compbio.mit.edu/HaploReg) to aid the functional dissection of genome-wide association study (GWAS) results, the prediction of putative causal variants in haplotype blocks, the prediction of likely cell types of action, and the prediction of candidate target genes by systematic mining of comparative, epigenomic and regulatory annotations. Since first launching the website in 2011, we have greatly expanded HaploReg, increasing the number of chromatin state maps to 127 reference epigenomes from ENCODE 2012 and Roadmap Epigenomics, incorporating regulator binding data, expanding regulatory motif disruption annotations, and integrating expression quantitative trait locus (eQTL) variants and their tissue-specific target genes from GTEx, Geuvadis, and other recent studies. We present these updates as HaploReg v4, and illustrate a use case of HaploReg for attention deficit hyperactivity disorder (ADHD)-associated SNPs with putative brain regulatory mechanisms. PMID:26657631

  1. In silico Analysis of Candidate Genes Involved in Sanfilippo Syndrome

    Directory of Open Access Journals (Sweden)

    Mehreen Zaka

    2015-04-01

    Full Text Available Sanfilippo syndrome is an autosomal recessive lysosomal storage disorder, caused by the deficiency of enzymes that play an important role in degradation of glycosaminoglycans and also called mucopolysaccharidosis III. Mucopolysaccharidosis is genetic disorder. Here, we searched the candidate genes for Sanfilippo syndrome by using BLAST with the query sequence. As no suitable homology was found against the query sequence we moved towards threading approach. The threading approach was carried out by employing online CPH models and LOMETS tools. Through present research, domains of the proteins were predicted by utilizing the Domain Sweep tools, GNS and two domains were reported. Motif search reported the maximum number of motifs for Type D protein as compared to other types. All four proteins were totally soluble proteins and no transmembrane domains were found. In future, these results and predicted 3D structures can be used for the molecular docking studies, binding activities and protein-protein interactions for all the four types of Sanfilippo syndrome.

  2. Cloning and Characterization of a Putative CTR1 Gene from Wheat

    Institute of Scientific and Technical Information of China (English)

    BI Cai-li; WEN Xiao-jie; ZHANG Xue-yong; LIU Xu

    2010-01-01

    CTR1 is a key negative regulator in ethylene signal transduction.A salt-induced CTR1 like gene(TaCTR1)was cloned from wheat,its expression under abiotie stresses,subcellular localization and the effect of overexpression of TaCTR1 on salt tolerance in tobacco was studied.A putative CTR1 gene was cloned and characterized from wheat via rapid amplification of cDNA ends(RACE)and RT-PCR.TaCTR1 expression under stresses was analyzed using semi-quantitative RT-PCR and the effect of overexpression of TaCTR1 on salt tolerance was conducted in tobacco.The full-length cDNA of TaCTR1is 2635 bp which codes for a polypeptide of 759 amino acids.There is a conserved serine/threonine protein kinase domain at the carboxyl terminus containing an ATP-binding site.Southern blot analysis revealed that TaCTR1 consisted of a gene family in wheat.The amino acid homologies of CTR1 among different organisms share higher similarities.Expression analysis revealed that TaCTR1 was induced by NaCl and drought stress but inhibited by ABA treatment.Transient expression of TaCTR1-GFP in the onion epidermal cells indicated that TaCTR1 was probably targeted to the plasma membrane.Overexpression of TaCTR1 decreased salt tolerance in transgenic tobacco(Nicotiana tabacum L.)plants compared with the control.To our knowledge,TaCTR1 is the first CTR1 gene cloned in wheat and may be involved in various abiotic stresses.Overexpression of TaCTR1 decreased the salt tolerance in tobacco suggested that TaCTR1 may act as a negative regulator of salt stress in plants.

  3. A putative plant organelle RNA recognition protein gene is essential for maize kernel development

    Institute of Scientific and Technical Information of China (English)

    Antony M Chettoor; Gibum Yi; Elisa Gomez; Gregorio Hueros; Robert B Meeley; Philip W Becraft

    2015-01-01

    Basal endosperm transfer layer (BETL) cel s are responsible for transferring apoplastic solutes from the maternal pedicel into the endosperm, supplying the grain with compounds required for embryo development and storage reserve accumulation. Here, we analyze the maize (Zea mays L.) empty pericarp6 (emp6) mutant, which causes early arrest in grain development. The Emp6þgene function is required independently in both the embryo and endo-sperm. The emp6 mutant causes a notable effect on the differentiation of BETL cel s; the extensive cel wal ingrowths that distinguish BETL cel s are diminished and BETL marker gene expression is compromised in mutant kernels. Transposon tagging identified the emp6 locus as encoding a putative plant organel e RNA recognition (PORR) protein, 1 of 15 PORR family members in maize. The emp6 transcript is widely detected in plant tissues with highest levels in embryos and developing kernels. EMP6‐green fluorescent protein (GFP) fusion proteins transiently expressed in Nicotiana benthamiana leaves were targeted specifical y to mitochondria. These results suggest that BETL cel differentia-tion might be particularly energy intensive, or alternatively, that mitochondria might confer a developmental function.

  4. Gene-level integrated metric of negative selection (GIMS) prioritizes candidate genes for nephrotic syndrome.

    Science.gov (United States)

    Sampson, Matthew G; Gillies, Christopher E; Ju, Wenjun; Kretzler, Matthias; Kang, Hyun Min

    2013-01-01

    Nephrotic syndrome (NS) gene discovery efforts are now occurring in small kindreds and cohorts of sporadic cases. Power to identify causal variants in these groups beyond a statistical significance threshold is challenging due to small sample size and/or lack of family information. There is a need to develop novel methods to identify NS-associated variants. One way to determine putative functional relevance of a gene is to measure its strength of negative selection, as variants in genes under strong negative selection are more likely to be deleterious. We created a gene-level, integrated metric of negative selection (GIMS) score for 20,079 genes by combining multiple comparative genomics and population genetics measures. To understand the utility of GIMS for NS gene discovery, we examined this score in a diverse set of NS-relevant gene sets. These included genes known to cause monogenic forms of NS in humans as well as genes expressed in the cells of the glomerulus and, particularly, the podocyte. We found strong negative selection in the following NS-relevant gene sets: (1) autosomal-dominant Mendelian focal segmental glomerulosclerosis (FSGS) genes (p = 0.03 compared to reference), (2) glomerular expressed genes (p = 4×10(-23)), and (3) predicted podocyte genes (p = 3×10(-9)). Eight genes causing autosomal dominant forms of FSGS had a stronger combined score of negative selection and podocyte enrichment as compared to all other genes (p = 1 x 10(-3)). As a whole, recessive FSGS genes were not enriched for negative selection. Thus, we also created a transcript-level, integrated metric of negative selection (TIMS) to quantify negative selection on an isoform level. These revealed transcripts of known autosomal recessive disease-causing genes that were nonetheless under strong selection. We suggest that a filtering strategy that includes measuring negative selection on a gene or isoform level could aid in identifying NS-related genes. Our GIMS and TIMS scores are

  5. Molecular cloning and primary sequence analysis of a gene encoding a putative shitinase gene in Brassica oleracea var.capitata

    Institute of Scientific and Technical Information of China (English)

    TANGGUOQING; YONGYANBAI; 等

    1996-01-01

    Chitinase,which catalyzes the hydrolysis of the β-1,4-acetyl-D-glucosamine linkages of the fungal cell wall polymer chitin,is involved in inducible plants defense system.By construction of cabbage(Brassica oleracea var. capitata) genomic library and screening the library with pRCH8,a probe of rice chitinase gene fragment,a chitinase genomic sequence was isolated.The complete uncleotide sequence of the putative cabbage chitinase gene (cabch29) was determined,with its longest open reading frame (ORF) encoding a polypeptide of 413 aa.This polypeptide consists of a 21 aa N-terminal signal peptide,two chitin-binding domains different from those of other classes of plant chitinases,and a catalytic domain.Homology analysis illustrated that this cabch29 gene has 58.8% identity at the nucleotide level with the pRCH8 ORF probe and has 50% identity at the amino acid level tiwh the catalytic domains of chitinase from bean,maize and sugar beet.Meanwhile,several kinds of cis-elements,such as TATA box,CAAT box,GATA motif,ASF-1 binding site,wound-response elements and AATAAA,have also been discovered in the flanking region of cabch29 gene.

  6. Cloning and sequence analysis of putative type II fatty acid synthase genes from Arachis hypogaea L.

    Indian Academy of Sciences (India)

    Meng-Jun Li; Ai-Qin Li; Han Xia; Chuan-Zhi Zhao; Chang-Sheng Li; Shu-Bo Wan; Yu-Ping Bi; Xing-Jun Wang

    2009-06-01

    The cultivated peanut is a valuable source of dietary oil and ranks fifth among the world oil crops. Plant fatty acid biosynthesis is catalysed by type II fatty acid synthase (FAS) in plastids and mitochondria. By constructing a full-length cDNA library derived from immature peanut seeds and homology-based cloning, candidate genes of acyl carrier protein (ACP), malonyl-CoA:ACP transacylase, -ketoacyl-ACP synthase (I, II, III), -ketoacyl-ACP reductase, -hydroxyacyl-ACP dehydrase and enoyl-ACP reductase were isolated. Sequence alignments revealed that primary structures of type II FAS enzymes were highly conserved in higher plants and the catalytic residues were strictly conserved in Escherichia coli and higher plants. Homologue numbers of each type II FAS gene expressing in developing peanut seeds varied from 1 in KASII, KASIII and HD to 5 in ENR. The number of single-nucleotide polymorphisms (SNPs) was quite different in each gene. Peanut type II FAS genes were predicted to target plastids except ACP2 and ACP3. The results suggested that peanut may contain two type II FAS systems in plastids and mitochondria. The type II FAS enzymes in higher plants may have similar functions as those in E. coli.

  7. Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Jun

    2010-11-01

    Full Text Available Abstract Background To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC, we performed a genome-wide survey and found that Myelin and lymphocyte-associated protein (MAL was a gene that was markedly down-regulated in HNSCC. Hence, we investigated the mechanism of MAL silencing and the effects of MAL on the proliferation, invasion, and apoptotic potential in HNSCC. Results MAL was significantly down-regulated in 91.7% of HNSCC specimens at the mRNA level as compared with adjacent normal tissues (P = 0.0004. Moreover, the relative transcript levels of the MAL gene were remarkably decreased by five-fold in nine HNSCC cell lines as compared with normal head and neck epithelium cells. MAL gene expression was restored in 44%, 67%, and 89% in HNSCC cell lines treated with TSA, 5-Aza-dC, and TSA plus 5-Aza-dC, respectively. Furthermore, bisulfate-treated DNA sequencing demonstrated that the two CpG islands (that is, M1 and M2 located in MAL promoter region were completely methylated in the HNSCC cell lines (CpG methylated ratio was more than 90%, and only one CpG island (that is, M1 was partially methylated in HNSCC tissues (CpG methylated ratio between 20% and 90%. A significant reduction in cell proliferation and a change in the cell cycle profile were also observed in MAL transfectants. Matrigel assay demonstrated that the invasiveness of HNSCC cells significantly decreased. A significant increase in the population of apoptotic cells was observed in MAL transfected cells. The exogenous expression of the MAL gene suppressed malignant phenotypes, while the cell death induced by MAL gene transfer was a result of apoptosis as demonstrated by the induction of cleavage of the poly (that is, ADP-ribose polymerase. Additionally, tumor growth was suppressed in cells expressing MAL as compared with cells not expressing MAL. Conclusion Our data suggest that the epigenetic inactivation of MAL, as a candidate tumor

  8. Differential transcript abundance and genotypic variation of four putative allergen-encoding gene families in melting peach

    NARCIS (Netherlands)

    Yang, Z.; Ma, Y.; Chen, L.; Xie, R.; Zhang, X.; Zhang, B.; Lu, M.; Wu, S.; Gilissen, L.J.W.J.; Ree, van R.; Gao, Z.

    2011-01-01

    We analysed the temporal and spatial transcript expression of the panel of 18 putative isoallergens from four gene families (Pru p 1–4) in the peach fruit, anther and leaf of two melting cultivars, to gain insight into their expression profiles and to identify the key family members. Genotypic varia

  9. Genome sequencing of a virulent avian Pasteurella multocida strain GX-Pm reveals the candidate genes involved in the pathogenesis.

    Science.gov (United States)

    Yu, Chengjie; Sizhu, Suolang; Luo, Qingping; Xu, Xuewen; Fu, Lei; Zhang, Anding

    2016-04-01

    Pasteurella multocida (P. multocida) was first shown to be the causative agent of fowl cholera by Louis Pasteur in 1881. First genomic study was performed on an avirulent avian strain Pm70, and until 2013, two genomes of virulent avian strains X73 and P1059 were sequenced. Comparative genome study supplied important information for further study on the pathogenesis of fowl cholera. In the previous study, a capsular serotype A strain GX-Pm was isolated from the liver of a chicken, which died during an outbreak of fowl cholera in 2011. The strain showed multiple drug resistance and was highly virulent to chickens. Therefore, the present study performed the genome sequencing and a comparative genomic analysis to reveal the candidate genes involved in virulence of P. multocida. Sequenced draft genome sequence of GX-Pm was 2,292,886 bp, contained 2941 protein-coding genes, 5 genomic islands, 4 IS elements and 2 prophage regions. Notability, all the predicted drug-resistance genes were included in predicted genomic islands. A comparative genome study on virulent avian strains P1059, X73 and GX-Pm with the avirulent avian strain Pm 70 indicated that 475 unique genes were only identified in either of virulent strains but absent in the avirulent strain. Among these genes, 20 genes were contained within genomes of all three virulent strains, including a few of putative virulence genes. Further characterization of the pathogenic functions of these genes would benefit the understanding of pathogenesis of fowl cholera. PMID:27033902

  10. Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

    Directory of Open Access Journals (Sweden)

    Steinmetz André

    2010-09-01

    Full Text Available Abstract Background Plants of the Huperziaceae family, which comprise the two genera Huperzia and Phlegmariurus, produce various types of lycopodium alkaloids that are used to treat a number of human ailments, such as contusions, swellings and strains. Huperzine A, which belongs to the lycodine type of lycopodium alkaloids, has been used as an anti-Alzheimer's disease drug candidate. Despite their medical importance, little genomic or transcriptomic data are available for the members of this family. We used massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform to generate a substantial EST dataset for Huperzia serrata (H. serrata and Phlegmariurus carinatus (P. carinatus as representative members of the Huperzia and Phlegmariurus genera, respectively. H. serrata and P. carinatus are important plants for research on the biosynthesis of lycopodium alkaloids. We focused on gene discovery in the areas of bioactive compound biosynthesis and transcriptional regulation as well as genetic marker detection in these species. Results For H. serrata, 36,763 unique putative transcripts were generated from 140,930 reads totaling over 57,028,559 base pairs; for P. carinatus, 31,812 unique putative transcripts were generated from 79,920 reads totaling over 30,498,684 base pairs. Using BLASTX searches of public databases, 16,274 (44.3% unique putative transcripts from H. serrata and 14,070 (44.2% from P. carinatus were assigned to at least one protein. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG orthology annotations revealed that the functions of the unique putative transcripts from these two species cover a similarly broad set of molecular functions, biological processes and biochemical pathways. In particular, a total of 20 H. serrata candidate cytochrome P450 genes, which are more abundant in leaves than in roots and might be involved in lycopodium alkaloid biosynthesis, were found based on the comparison of H

  11. The putative phosphoinositide-specific phospholipase C gene, PLC1, of the yeast Saccharomyces cerevisiae is important for cell growth.

    OpenAIRE

    Yoko-o, T; Matsui, Y; Yagisawa, H; Nojima, H; Uno, I; Toh-E, A

    1993-01-01

    Using the polymerase chain reaction technique, we have isolated a gene that encodes a putative phosphoinositide-specific phospholipase C (PLC) in the yeast Saccharomyces cerevisiae. The nucleotide sequence indicates that the gene encodes a polypeptide of 869 amino acid residues with a calculated molecular mass of 101 kDa. This polypeptide has both the X and Y regions conserved among mammalian PLC-beta, -gamma, and -delta, and the structure is most similar to that of mammalian PLC-delta. This ...

  12. RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Bignone, P A; Lee, K Y; Liu, Y;

    2007-01-01

    We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen...

  13. Differential Gene Expression Reveals Candidate Genes for Drought Stress Response in Abies alba (Pinaceae)

    OpenAIRE

    David Behringer; Heike Zimmermann; Birgit Ziegenhagen; Sascha Liepelt

    2015-01-01

    Increasing drought periods as a result of global climate change pose a threat to many tree species by possibly outpacing their adaptive capabilities. Revealing the genetic basis of drought stress response is therefore implemental for future conservation strategies and risk assessment. Access to informative genomic regions is however challenging, especially for conifers, partially due to their large genomes, which puts constraints on the feasibility of whole genome scans. Candidate genes offer...

  14. RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population.

    Science.gov (United States)

    Li, Cong; Cai, Wentao; Zhou, Chenghao; Yin, Hongwei; Zhang, Ziqi; Loor, Juan J; Sun, Dongxiao; Zhang, Qin; Liu, Jianfeng; Zhang, Shengli

    2016-06-02

    Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration. Integrated interpretation of differential gene expression indicated that SERPINA1, CLU, CNTFR, ERBB2, NEDD4L, ANG, GALE, HSPA8, LPAR6 and CD14 are the most promising candidate genes affecting milk protein concentration. Similarly, LTF, FCGR3A, MEGF10, RRM2 and UBE2C are the most promising candidates that in the non-lactating period could help the mammary tissue prevent issues with inflammation and udder disorders. Putative genes will be valuable resources for designing better breeding strategies to optimize the content of milk protein and also to provide new insights into regulation of lactogenesis.

  15. Linkage mapping of putative regulator genes of barley grain development characterized by expression profiling

    Directory of Open Access Journals (Sweden)

    Wobus Ulrich

    2009-01-01

    Full Text Available Abstract Background Barley (Hordeum vulgare L. seed development is a highly regulated process with fine-tuned interaction of various tissues controlling distinct physiological events during prestorage, storage and dessication phase. As potential regulators involved within this process we studied 172 transcription factors and 204 kinases for their expression behaviour and anchored a subset of them to the barley linkage map to promote marker-assisted studies on barley grains. Results By a hierachical clustering of the expression profiles of 376 potential regulatory genes expressed in 37 different tissues, we found 50 regulators preferentially expressed in one of the three grain tissue fractions pericarp, endosperm and embryo during seed development. In addition, 27 regulators found to be expressed during both seed development and germination and 32 additional regulators are characteristically expressed in multiple tissues undergoing cell differentiation events during barley plant ontogeny. Another 96 regulators were, beside in the developing seed, ubiquitously expressed among all tissues of germinating seedlings as well as in reproductive tissues. SNP-marker development for those regulators resulted in anchoring 61 markers on the genetic linkage map of barley and the chromosomal assignment of another 12 loci by using wheat-barley addition lines. The SNP frequency ranged from 0.5 to 1.0 SNP/kb in the parents of the various mapping populations and was 2.3 SNP/kb over all eight lines tested. Exploration of macrosynteny to rice revealed that the chromosomal orders of the mapped putative regulatory factors were predominantly conserved during evolution. Conclusion We identified expression patterns of major transcription factors and signaling related genes expressed during barley ontogeny and further assigned possible functions based on likely orthologs functionally well characterized in model plant species. The combined linkage map and reference

  16. Exclusion of the PAX2 gene as a candidate gene for Crouzon craniofacial dysostosis

    Energy Technology Data Exchange (ETDEWEB)

    Preston, R.A.; Gorry, M.C. [Univ. of Pittsburgh, PA (United States); Warman, M. [Harvard Univ., Boston, MA (United States)] [and others

    1994-09-01

    Crouzon craniofacial dysostosis (CFD, MIM 123500) is an abnormality of craniofacial development characterized by premature craniosynostosis, maxillary hypoplasia, and shallow orbits. We have mapped the CFD gene locus using a candidate gene approach to a 7 centiMorgan region on chromosome 10q in three CFD families. A maximal multipoint LOD score of 12.33 was achieved for a locus 2 cM distal to the microsatellite marker D10S209. A comparison of several physical, cytogenetic, and linkage maps revealed that the cytogenetic bands, 10q25-q26, most likely contain this CFD locus. The PAX2 gene, which has been mapped near another marker which in turn has been mapped to 10q25, was analyzed as a candidate gene. PAX2 was chosen for analysis because mutations in other members of the PAX gene family have been identified with human craniofacial abnormalities (e.g. Waardenburg syndrome). A YAC contig, consisting of 5 overlapping groups and composed of 11 YACs that spans the entire 7 cM region, was assembled for PAX2 analyses. None of these YACs supported PAX2-specific amplification using primer sets for both the second and third PAX2 exons. Control amplifications for YAC vector sequences produced robust amplifications in all cases. In addition, SSCP analyses of amplification products generated from the second and third PAX2 exons and the 3{prime} untranslated region of the PAX2 gene from both affected and unaffected family members in two of the kindreds failed to reveal any polymorphisms. Although it remains theoretically possible, due to artifacts in the YAC contigs, it is unlikely that PAX2 is the CFD gene.

  17. Fine mapping and candidate gene analysis of purple pericarp gene Pb in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Purple rice is a type of rice with anthocyanins deposited in its grain pericarp. The rice Pb gene controlling purple pericarp character is known to be on chromosome 4, and the purple color is dominant over white color. In this study, we fine mapped the Pb gene using two F2 segregating populations, i.e. Pei'ai 64S (white) × Yunanheixiannuo (purple) and Pei'ai 64S × Chuanheinuo (purple). In the first-pass mapping, the Pb gene was located in the region downstream the SSR marker RM3820. In the fine mapping, the candidate region was saturated with InDel and CAPS markers developed specifically for this study. Eventually, the Pb gene was mapped within the 25-kb region delimited by the upstream marker RID3 and the downstream marker RID4. The delimited region contained two annotated genes, Ra and bhlh16 (TIGR Rice Genome, R.5). The former is a homologue of the Myc transcription factor Lc controlling anthocyanin biosynthesis in maize, and the latter is a homologue of the TT8 gene, which is also an Myc transcription factor gene controlling the pericarp pigmentation in Arabidopsis thaliana. Sequence analysis showed that the exon 7 of the Ra gene of Yunanheixiannuo and Chuanheinuo had a 2-bp (GT) deletion compared with those of the white rice varieties Pei'ai 64S, 9311 and Nipponbare. A CAPS marker, CAPSRa, was developed according to the GT deletion for analysis of the two F2 segregating populations and 106 rice lines. The results showed that all F2 plants with white pericarp, and all non-purple rice lines (63 white and 22 red) contained no GT deletion, but all 20 purple rice lines contained the GT deletion. These results suggested that the Ra gene may be the Pb gene and the purple pericarp characteristic of rice is caused by the GT deletion within exon 7 of the Ra gene.

  18. Identification of Candidate Genes related to Bovine Marbling using Protein-Protein Interaction Networks

    OpenAIRE

    Lim, Dajeong; Kim, Nam-Kuk; Park, Hye-Sun; Lee, Seung-Hwan; Cho, Yong-Min; Oh, Sung Jong; Kim, Tae-Hun; Kim, Heebal

    2011-01-01

    Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The present study systemically analyzed genes associated with bovine marbling score and identified their relationships. The candidate nodes were obtained using MedScan text-mining tools and linked by protein-protein intera...

  19. Molecular genetic gene-environment studies using candidate genes in schizophrenia: a systematic review.

    Science.gov (United States)

    Modinos, Gemma; Iyegbe, Conrad; Prata, Diana; Rivera, Margarita; Kempton, Matthew J; Valmaggia, Lucia R; Sham, Pak C; van Os, Jim; McGuire, Philip

    2013-11-01

    The relatively high heritability of schizophrenia suggests that genetic factors play an important role in the etiology of the disorder. On the other hand, a number of environmental factors significantly influence its incidence. As few direct genetic effects have been demonstrated, and there is considerable inter-individual heterogeneity in the response to the known environmental factors, interactions between genetic and environmental factors may be important in determining whether an individual develops the disorder. To date, a considerable number of studies of gene-environment interactions (G×E) in schizophrenia have employed a hypothesis-based molecular genetic approach using candidate genes, which have led to a range of different findings. This systematic review aims to summarize the results from molecular genetic candidate studies and to review challenges and opportunities of this approach in psychosis research. Finally, we discuss the potential of future prospects, such as new studies that combine hypothesis-based molecular genetic candidate approaches with agnostic genome-wide association studies in determining schizophrenia risk.

  20. Microphthalmia with linear skin defects syndrome (MLS): Characterization of the critical region and isolation of candidate genes

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, L.; Wapenaar, M.C.; Grillo, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder characterized by abnormalities in the development of the eye, skin, and brain. We defined the MLS critical region through analysis of hybrid cell lines retaining various deletion breakpoints in Xp22, including cell lines from 17 female patients showing features of MLS. Using a combination of YAC cloning and long-range restriction analysis, the MLS candidate region was estimated to be 450-550 kb. A minimally overlapping cosmid contig comprised of 20 cosmid clones was subsequently developed in this region. These cosmids are currently being used to isolate expressed sequences using cross-species conservation studies and exon-trapping. An evolutionarily conserved sequence isolated from a cosmid within the critical region has been used to isolate several overlapping cDNAs from a human embryonic library. Northern analysis using these cDNA clones identified a 5.2 kb transcript in all tissues examined. Sequence analysis revealed a 777 base pair open reading frame encoding a putative 258 amino acid protein. Using the exon-trapping method, fifty-four putative exons have been isolated from fourteen cosmids within the critical region. The expression patterns of the genes containing these exons are being analyzed by polymerase chain reaction (PCR) using reverse-transcribed mRNA from several human tissues and primers corresponding to the exon sequences. Using this approach in combination with exon connection, we determined the four of the trapped exons belong to the same cDNA transcript, which is expressed in adult retina, lymphoblast, skeletal muscle, and fetal brain. To date, we have isolated and sequenced 1 kilobase of this gene, all of which appears to be open reading frame. Both of the genes isolated from the critical region are being analyzed as possible candidates for MLS.

  1. Identification of candidate methylation-responsive genes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dickerson Erin B

    2007-01-01

    Full Text Available Abstract Background Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers. Results In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3 before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC. An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified. Conclusion We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.

  2. De Novo assembly of the Japanese flounder (Paralichthys olivaceus spleen transcriptome to identify putative genes involved in immunity.

    Directory of Open Access Journals (Sweden)

    Lin Huang

    Full Text Available Japanese flounder (Paralichthys olivaceus is an economically important marine fish in Asia and has suffered from disease outbreaks caused by various pathogens, which requires more information for immune relevant genes on genome background. However, genomic and transcriptomic data for Japanese flounder remain scarce, which limits studies on the immune system of this species. In this study, we characterized the Japanese flounder spleen transcriptome using an Illumina paired-end sequencing platform to identify putative genes involved in immunity.A cDNA library from the spleen of P. olivaceus was constructed and randomly sequenced using an Illumina technique. The removal of low quality reads generated 12,196,968 trimmed reads, which assembled into 96,627 unigenes. A total of 21,391 unigenes (22.14% were annotated in the NCBI Nr database, and only 1.1% of the BLASTx top-hits matched P. olivaceus protein sequences. Approximately 12,503 (58.45% unigenes were categorized into three Gene Ontology groups, 19,547 (91.38% were classified into 26 Cluster of Orthologous Groups, and 10,649 (49.78% were assigned to six Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, 40,928 putative simple sequence repeats and 47, 362 putative single nucleotide polymorphisms were identified. Importantly, we identified 1,563 putative immune-associated unigenes that mapped to 15 immune signaling pathways.The P. olivaceus transciptome data provides a rich source to discover and identify new genes, and the immune-relevant sequences identified here will facilitate our understanding of the mechanisms involved in the immune response. Furthermore, the plentiful potential SSRs and SNPs found in this study are important resources with respect to future development of a linkage map or marker assisted breeding programs for the flounder.

  3. Identification of candidate B-lymphoma genes by cross-species gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Van S Tompkins

    Full Text Available Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL and Burkitt lymphoma (BL. We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the "mouse filter" for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists.

  4. Validation of putative reference genes for normalization of Q-RT-PCR data from paraffin-embedded lymphoid tissue

    DEFF Research Database (Denmark)

    Green, Tina Marie; de Stricker, Karin; Møller, Michael Boe

    2009-01-01

    Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to appropriate tissue-specific reference genes is an essential part of interpreting the results. This study aimed to determine the most appropriate reference genes for normalizing gene expressions in lymphatic tissue......, represented by non-neoplastic lymph nodes and diffuse large B-cell lymphomas, by using 2 statistical software applications, geNorm and NormFinder. In addition, we wanted to validate the usefulness of paraffin-embedded samples for Q-RT-PCR studies by investigating gene expressions of relevant target genes...... in paired frozen and paraffin-embedded samples. Moreover, we studied the impact of amplicon sizes on the efficiency of Q-RT-PCR in paraffin-embedded tissues. Six putative reference genes were tested for stability of expression in 21 pairs of snap-frozen and formalin-fixed, paraffin-embedded lymph nodes...

  5. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  6. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage;

    2014-01-01

    Residual feed intake (RFI) is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and...... biological pathways involved in regulating RFI using Genome-wide association (GWA) and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2) and 60k genotypic data was used. Genome-wide association analysis was performed using a univariate mixed model...... and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as XIRP2, TTC29, SOGA1, MAS1, GRK5, PROX1, GPR155 and ZFYVE26 were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located...

  7. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    OpenAIRE

    Giovannetti Marco; Balestrini Raffaella; Volpe Veronica; Guether Mike; Straub Daniel; Costa Alex; Ludewig Uwe; Bonfante Paola

    2012-01-01

    Abstract Background Arbuscular mycorrhizas (AM) are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus...

  8. Expression of the dyslexia candidate gene kiaa0319-like in insect cells

    NARCIS (Netherlands)

    Holster, S.; Oers, van M.M.; Roode, E.C.; Tsang, O.W.H.; Yeung, V.S.Y.; Vlak, J.M.; Waye, M.M.Y.

    2013-01-01

    The human kiaa0319-like gene is one of the candidate genes for developmental dyslexia, but the exact function of the encoded KIAA0319L (KL) protein is not known. To allow functional analysis a purified, biologically active KL protein is required. The kiaa0319-like gene was expressed in insect cells

  9. Epidermal growth factor gene is a newly identified candidate gene for gout.

    Science.gov (United States)

    Han, Lin; Cao, Chunwei; Jia, Zhaotong; Liu, Shiguo; Liu, Zhen; Xin, Ruosai; Wang, Can; Li, Xinde; Ren, Wei; Wang, Xuefeng; Li, Changgui

    2016-01-01

    Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67-0.88, Padjusted = 6.42 × 10(-3)). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations. PMID:27506295

  10. Transcriptome-Wide Survey and Expression Profile Analysis of Putative Chrysanthemum HD-Zip I and II Genes

    Directory of Open Access Journals (Sweden)

    Aiping Song

    2016-05-01

    Full Text Available The homeodomain-leucine zipper (HD-Zip transcription factor family is a key transcription factor family and unique to the plant kingdom. It consists of a homeodomain and a leucine zipper that serve in combination as a dimerization motif. The family can be classified into four subfamilies, and these subfamilies participate in the development of hormones and mediation of hormone action and are involved in plant responses to environmental conditions. However, limited information on this gene family is available for the important chrysanthemum ornamental species (Chrysanthemum morifolium. Here, we characterized 17 chrysanthemum HD-Zip genes based on transcriptome sequences. Phylogenetic analyses revealed that 17 CmHB genes were distributed in the HD-Zip subfamilies I and II and identified two pairs of putative orthologous proteins in Arabidopsis and chrysanthemum and four pairs of paralogous proteins in chrysanthemum. The software MEME was used to identify 7 putative motifs with E values less than 1e-3 in the chrysanthemum HD-Zip factors, and they can be clearly classified into two groups based on the composition of the motifs. A bioinformatics analysis predicted that 8 CmHB genes could be targeted by 10 miRNA families, and the expression of these 17 genes in response to phytohormone treatments and abiotic stresses was characterized. The results presented here will promote research on the various functions of the HD-Zip gene family members in plant hormones and stress responses.

  11. Transcriptome-Wide Survey and Expression Profile Analysis of Putative Chrysanthemum HD-Zip I and II Genes.

    Science.gov (United States)

    Song, Aiping; Li, Peiling; Xin, Jingjing; Chen, Sumei; Zhao, Kunkun; Wu, Dan; Fan, Qingqing; Gao, Tianwei; Chen, Fadi; Guan, Zhiyong

    2016-01-01

    The homeodomain-leucine zipper (HD-Zip) transcription factor family is a key transcription factor family and unique to the plant kingdom. It consists of a homeodomain and a leucine zipper that serve in combination as a dimerization motif. The family can be classified into four subfamilies, and these subfamilies participate in the development of hormones and mediation of hormone action and are involved in plant responses to environmental conditions. However, limited information on this gene family is available for the important chrysanthemum ornamental species (Chrysanthemum morifolium). Here, we characterized 17 chrysanthemum HD-Zip genes based on transcriptome sequences. Phylogenetic analyses revealed that 17 CmHB genes were distributed in the HD-Zip subfamilies I and II and identified two pairs of putative orthologous proteins in Arabidopsis and chrysanthemum and four pairs of paralogous proteins in chrysanthemum. The software MEME was used to identify 7 putative motifs with E values less than 1e-3 in the chrysanthemum HD-Zip factors, and they can be clearly classified into two groups based on the composition of the motifs. A bioinformatics analysis predicted that 8 CmHB genes could be targeted by 10 miRNA families, and the expression of these 17 genes in response to phytohormone treatments and abiotic stresses was characterized. The results presented here will promote research on the various functions of the HD-Zip gene family members in plant hormones and stress responses. PMID:27196930

  12. Candidate gene prioritization by network analysis of differential expression using machine learning approaches

    Directory of Open Access Journals (Sweden)

    Nitsch Daniela

    2010-09-01

    Full Text Available Abstract Background Discovering novel disease genes is still challenging for diseases for which no prior knowledge - such as known disease genes or disease-related pathways - is available. Performing genetic studies frequently results in large lists of candidate genes of which only few can be followed up for further investigation. We have recently developed a computational method for constitutional genetic disorders that identifies the most promising candidate genes by replacing prior knowledge by experimental data of differential gene expression between affected and healthy individuals. To improve the performance of our prioritization strategy, we have extended our previous work by applying different machine learning approaches that identify promising candidate genes by determining whether a gene is surrounded by highly differentially expressed genes in a functional association or protein-protein interaction network. Results We have proposed three strategies scoring disease candidate genes relying on network-based machine learning approaches, such as kernel ridge regression, heat kernel, and Arnoldi kernel approximation. For comparison purposes, a local measure based on the expression of the direct neighbors is also computed. We have benchmarked these strategies on 40 publicly available knockout experiments in mice, and performance was assessed against results obtained using a standard procedure in genetics that ranks candidate genes based solely on their differential expression levels (Simple Expression Ranking. Our results showed that our four strategies could outperform this standard procedure and that the best results were obtained using the Heat Kernel Diffusion Ranking leading to an average ranking position of 8 out of 100 genes, an AUC value of 92.3% and an error reduction of 52.8% relative to the standard procedure approach which ranked the knockout gene on average at position 17 with an AUC value of 83.7%. Conclusion In this study we

  13. Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease.

    Directory of Open Access Journals (Sweden)

    Nicholette D Palmer

    Full Text Available Type 2 diabetes (T2D-associated end-stage kidney disease (ESKD is a complex disorder resulting from the combined influence of genetic and environmental factors. This study contains a comprehensive genetic analysis of putative nephropathy loci in 965 African American (AA cases with T2D-ESKD and 1029 AA population-based controls extending prior findings. Analysis was based on 4,341 directly genotyped and imputed single nucleotide polymorphisms (SNPs in 22 nephropathy candidate genes. After admixture adjustment and correction for multiple comparisons, 37 SNPs across eight loci were significantly associated (1.6E-05candidate loci (FRMD3 and TRPC6 trended toward association with T2D-ESKD (P(emp<0.05. These results suggest that risk contributed by putative nephropathy genes is shared across populations of African and European ancestry.

  14. Predicting sensation seeking from dopamine genes: A candidate system approach

    OpenAIRE

    Derringer, Jaime; Robert F Krueger; Dick, Danielle M; Saccone, Scott; Grucza, Richard A.; Agrawal, Arpana; Lin, Peng; Almasy, Laura; Edenberg, Howard J.; Foroud, Tatiana; Nurnberger, John I.; Hesselbrock, Victor M.; Kramer, John R.; Kuperman, Samuel; Porjesz, Bernice

    2010-01-01

    Sensation seeking is a heritable personality trait that has been reliably linked to behavior disorders. The dopamine system has been hypothesized to contribute to individual differences in sensation seeking, and both experimental and observational studies in humans and non-human animals provide evidence for this relationship. We present here a candidate-system approach to genetic association analysis of sensation seeking, in which single nucleotide polymorphisms (SNPs) from a number of dopami...

  15. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  16. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    Science.gov (United States)

    Siegel, Erin M; Riggs, Bridget M; Delmas, Amber L; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  17. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    Science.gov (United States)

    Siegel, Erin M; Riggs, Bridget M; Delmas, Amber L; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated.

  18. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    Directory of Open Access Journals (Sweden)

    Erin M Siegel

    Full Text Available Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2. A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003. Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated.

  19. Dickkopf-1 is an epigenetically silenced candidate tumor suppressor gene in medulloblastoma1

    OpenAIRE

    Vibhakar, Rajeev; Foltz, Greg; Yoon, Jae-Geun; Field, Lorie; Lee, Hwahyung; Ryu, Gi-Yung; Pierson, Jessica; Davidson, Beverly; Madan, Anup

    2007-01-01

    Medulloblastoma is a heterogeneous pediatric brain tumor with significant therapy-related morbidity, its five-year survival rates ranging from 30% to 70%. Improvement in diagnosis and therapy requires better understanding of medulloblastoma pathology. We used whole-genome microarray analysis to identify putative tumor suppressor genes silenced by epigenetic mechanisms in medulloblastoma. This analysis yielded 714 up-regulated genes in immortalized medulloblastoma cell line D283 on treatment w...

  20. SORBS1 gene, a new candidate for diabetic nephropathy

    DEFF Research Database (Denmark)

    Germain, Marine; Pezzolesi, Marcus G; Sandholm, Niina;

    2015-01-01

    AIMS/HYPOTHESIS: The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy. METHODS: We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy......-wide statistical significance. The 46 top hits (p gene were......-effect meta-analysed rs1326934-C allele OR for diabetic nephropathy was 0.83 (95% CI 0.72, 0.96; p = 0.009). CONCLUSIONS/INTERPRETATION: These data suggest that SORBS1 might be a gene involved in diabetic nephropathy....

  1. Application of a Colorimetric Assay to Identify Putative Ribofuranosylaminobenzene 5'-Phosphate Synthase Genes Expressed with Activity in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Bechard Matthew E.

    2003-01-01

    Full Text Available Tetrahydromethanopterin (H4MPT is a tetrahydrofolate analog originally discovered in methanogenic archaea, but later found in other archaea and bacteria. The extent to which H4MPT occurs among living organisms is unknown. The key enzyme which distinguishes the biosynthetic pathways of H4MPT and tetrahydrofolate is ribofuranosylaminobenzene 5'-phosphate synthase (RFAP synthase. Given the importance of RFAP synthase in H4MPT biosynthesis, the identification of putative RFAP synthase genes and measurement of RFAP synthase activity would provide an indication of the presence of H4MPT in untested microorganisms. Investigation of putative archaeal RFAP synthase genes has been hampered by the tendency of the resulting proteins to form inactive inclusion bodies in Escherichia coli. The current work describes a colorimetric assay for measuring RFAP synthase activity, and two modified procedures for expressing recombinant RFAP synthase genes to produce soluble, active enzyme. By lowering the incubation temperature during expression, RFAP synthase from Archaeoglobus fulgidus was produced in E. coli and purified to homogeneity. The production of active RFAP synthase from Methanothermobacter thermautotrophicus was achieved by coexpression of the gene MTH0830 with a molecular chaperone. This is the first direct biochemical identification of a methanogen gene that codes for an active RFAP synthase.

  2. Characterization of two poplar homologs of the GRAS/SCL gene, which encodes a transcription factor putatively associated with salt tolerance

    Directory of Open Access Journals (Sweden)

    Galovic V

    2015-12-01

    Full Text Available To cope with soil salinity, which is one of the most severe forms of abiotic stress, efforts are being undertaken to enhance the salt tolerance of economically important poplar clones in the Vojvodina region of Serbia. One approach is to screen nucleotide diversity in candidate genes (CG in several poplar clones of high economic importance to Serbia to search for associations with salt stress tolerance. As plant-specific GRAS/SCL transcription factors (TFs play diverse roles in abiotic stress resistance, two poplar homologs of GRAS/SCL TFs were chosen to differentiate the species background with respect to salt tolerance. A BLAST search of the Populus trichocarpa genome using the P. euphratica gene GRAS/SCL TF_GH611858 sequence identified two putative orthologs, Scaf_5 and Scaf_7, with identities of 100% and 94%, respectively. Primers were designed in identical sequences of Scaf_5 and Scaf_7 to amplify fragments of GRAS/SCL TF orthologs in four poplar clones that are economically important to Serbia. The primers spanned regions where, at least in P. trichocarpa, single nucleotide polymorphisms (SNPs are present, thereby increasing the probability of distinguishing Scaf_5 and Scaf_7 orthologs in the four clones. Alignments and analyses of the gene fragments revealed that both orthologs were representative of the genetic diversity between different poplar clones, and the identified SNP markers differentiated the four poplar clones with respect to salt tolerance.

  3. Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer

    OpenAIRE

    Erin M Siegel; Riggs, Bridget M; Delmas, Amber L.; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D.

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and ...

  4. Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome

    Directory of Open Access Journals (Sweden)

    L.V.S. Teixeira

    2011-08-01

    Full Text Available Marfan syndrome (MFS is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34 of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.

  5. Phylogenomic Study of Lipid Genes Involved in Microalgal Biofuel Production—Candidate Gene Mining and Metabolic Pathway Analyses

    OpenAIRE

    Barada Kanta Mishra; Bikram Kumar Parida; Prasanna Kumar Panda; Namrata Misra

    2012-01-01

    Optimizing microalgal biofuel production using metabolic engineering tools requires an in-depth understanding of the structure-function relationship of genes involved in lipid biosynthetic pathway. In the present study, genome-wide identification and characterization of 398 putative genes involved in lipid biosynthesis in Arabidopsis thaliana Chlamydomonas reinhardtii, Volvox carteri, Ostreococcus lucimarinus, Ostreococcus tauri and Cyanidioschyzon merolae was undertaken on the basis of their...

  6. Clinal Variation in phyB2, a Candidate Gene for Day-Length-Induced Growth Cessation and Bud Set, Across a Latitudinal Gradient in European Aspen (Populus tremula)

    OpenAIRE

    Ingvarsson, Pär K.; García, M. Victoria; Hall, David; Luquez, Virginia; Jansson, Stefan

    2006-01-01

    The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short-day-induced bud set and growth cessation in Populus. We characterized patterns of DNA sequence variation at the putative candidate gene phyB2 in 4 populations of European aspen ...

  7. Candidate genes for cross-resistance against DNA-damaging drugs

    DEFF Research Database (Denmark)

    Wittig, Rainer; Nessling, Michelle; Will, Rainer D;

    2002-01-01

    Drug resistance of tumor cells leads to major drawbacks in the treatment of cancer. To identify candidate genes for drug resistance, we compared the expression patterns of the drug-sensitive human malignant melanoma cell line MeWo and three derived sublines with acquired resistance to the DNA......-damaging agents cisplatin, etoposide, and fotemustine. Subarray analyses confirmed 57 candidate genes recovered from a genome-wide scan for differential expression. By specifically addressing cancer genes we retrieved another set of 209 candidates. Exemplary Northern blot studies indicated qualitative concordance...... converged in their expression patterns. A total of 110 genes was transiently or permanently deregulated in at least two resistant sublines. Fourteen genes displayed differential expression in all three of the sublines. We hypothesize that the variations in fotemustine and cisplatin resistance are based...

  8. Triterpenoid Saponin Biosynthetic Pathway Profiling and Candidate Gene Mining of the Ilex asprella Root Using RNA-Seq

    Directory of Open Access Journals (Sweden)

    Xiasheng Zheng

    2014-04-01

    Full Text Available Ilex asprella, which contains abundant α-amyrin type triterpenoid saponins, is an anti-influenza herbal drug widely used in south China. In this work, we first analysed the transcriptome of the I. asprella root using RNA-Seq, which provided a dataset for functional gene mining. mRNA was isolated from the total RNA of the I. asprella root and reverse-transcribed into cDNA. Then, the cDNA library was sequenced using an Illumina HiSeq™ 2000, which generated 55,028,452 clean reads. De novo assembly of these reads generated 51,865 unigenes, in which 39,269 unigenes were annotated (75.71% yield. According to the structures of the triterpenoid saponins of I. asprella, a putative biosynthetic pathway downstream of 2,3-oxidosqualene was proposed and candidate unigenes in the transcriptome data that were potentially involved in the pathway were screened using homology-based BLAST and phylogenetic analysis. Further amplification and functional analysis of these putative unigenes will provide insight into the biosynthesis of Ilex triterpenoid saponins.

  9. Candidate genes of hypertension with defective environmental expression

    Institute of Scientific and Technical Information of China (English)

    SUNYULIN; JOHANNETREMBLAY; 等

    1995-01-01

    Previous studies in our laboratory have demonstrated that the thermosensitivity locus cosegregates with blood pressure and that the elevated expression and restriction fragment length polymorphism of HSP70 gene are associated with hypertension.Cell protection against environmental stressors such as heat and chemicals is often accompanied by up-regulated expression of a wide spectrum of heat shock genes(HSP).To further investigate the interrelation between HSP expression and blood pressure regulation,we employed an effective method of cloning 2 potential hypertension-related HSPs.Synthetic oligonucleotides corresponding either to a highly-conserved region of the known HSP family or a repetitive sequence in the proteinencoding gene were used as target primers for polymerase chain reaction(PCR).cDNA prepared from heat-stressed and non-stressed vascular smooth muscle cells(VSMC)of Brown Norway rats(BN.1x)and spontaneously hypertensive rats(SHRp) respectively served as template in the reaction.The PCR products were subsequently analyzed in a single-stranded conformational polymorphism(SSCP) electrophoresing system.Differential gene expression in BN.1x and SHRp was seen on autoradiographs of SSCP gel by comparing the migration patterns of PCR-amplified DNA fragments.Using this technique,we also found that HSP27 and a new member of the large HSP gene family were differentially expressed in BN.1x and SHRp VSMC.

  10. Isolation, characterization, and structure analysis of a non-TIR-NBS-LRR encoding candidate gene from MYMIV-resistant Vigna mungo.

    Science.gov (United States)

    Maiti, Soumitra; Paul, Sujay; Pal, Amita

    2012-11-01

    Yellow mosaic disease of Vigna mungo caused by Mungbean yellow mosaic India virus (MYMIV) is still a major threat in the crop production. A candidate disease resistance (R) gene, CYR1 that co-segregates with MYMIV-resistant populations of V. mungo has been isolated. CYR1 coded in silico translated protein sequence comprised of 1,176 amino acids with coiled coil structure at the N-terminus, central nucleotide binding site (NBS) and C-terminal leucine-rich repeats (LRR) that belongs to non-TIR-NBS-LRR subfamily of plant R genes. CYR1 transcript was unambiguously expressed during incompatible plant virus interactions. A putative promoter-like sequence present upstream of this candidate gene perhaps regulates its expression. Enhanced transcript level upon MYMIV infection suggests involvement of this candidate gene in conferring resistance against the virus. In silico constructed 3D models of NBS and LRR regions of this candidate protein and MYMIV-coat protein (CP) revealed that CYR1-LRR forms an active pocket and successively interacts with MYMIV-CP during docking, like that of receptor-ligand interaction; indicating a critical role of CYR1 as signalling molecule to protect V. mungo plants from MYMIV. This suggests involvement of CYR1 in recognizing MYMIV-effector molecule thus contributing to incompatible interaction. This study is the first stride to understand molecular mechanism of MYMIV resistance.

  11. Analysis of gene expression during flowering in apomeiotic mutants of Medicago spp.: cloning of ESTs and candidate genes for 2n eggs.

    Science.gov (United States)

    Barcaccia, G; Varotto, S; Meneghetti, S; Albertini, E; Porceddu, A; Parrini, P; Lucchin, M

    2001-12-01

    Mutants showing features of apomixis have been documented in alfalfa (Medicago sativa L.), a natural outcrossing sexual species. A differential display of mRNAs that combines cDNA-AFLP markers and bulked segregant analysis was carried out with the aim of selecting expressed sequence tags (ESTs) and cloning candidate genes for apomeiosis in mutants of alfalfa characterized by 2n egg formation at high frequencies. The approach enabled us to select either mutant- or wild type-specific transcript derived-fragments and to detect transcriptional changes potentially related to 2n eggs. Sequence alignments of a subset of 40 polymorphic clones showed significant homologies to genes of known function. An EST with identity to a β-tubulin gene, highly expressed in the wild type and poorly expressed in the apomeiotic mutants, and an EST with identity to a Mob1-like gene, qualitatively polymorphic between pre- and post-meiotic stages, were selected as candidate genes for apomeiosis because of their putative roles in the cell cycle. A number of clone-specific primers were designed for performing both 5' and 3' rapid amplification of cDNA ends to obtain the full-length clones. Southern blot hybridization revealed that both clones belong to a multi-gene family with a minimum of three genomic DNA members each. Northern blot hybridization of total RNA samples and in situ hybridization of whole buds enabled the definition of their temporal and spatial expression patterns in reproductive organs. Experimental achievements towards the elucidation of apomeiotic megasporogenesis in alfalfa are presented and discussed.

  12. Characterizing gene-gene interactions in a statistical epistasis network of twelve candidate genes for obesity

    OpenAIRE

    Rishika; Hu, Ting; Moore, Jason H.; Gilbert-Diamond, Diane

    2015-01-01

    Background Recent findings have reemphasized the importance of epistasis, or gene-gene interactions, as a contributing factor to the unexplained heritability of obesity. Network-based methods such as statistical epistasis networks (SEN), present an intuitive framework to address the computational challenge of studying pairwise interactions between thousands of genetic variants. In this study, we aimed to analyze pairwise interactions that are associated with Body Mass Index (BMI) between SNPs...

  13. LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

    Institute of Scientific and Technical Information of China (English)

    DENG Hongwen; GAO Guimin

    2006-01-01

    The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2.0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

  14. Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning

    Directory of Open Access Journals (Sweden)

    Atkins John F

    2010-01-01

    Full Text Available Abstract Background Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community. Results Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae, Reoviridae, Rhabdoviridae and Coronaviridae, respectively.

  15. Bioinformatic Analysis of Putative Gene Products Encoded in SARS-HCoV Genome

    Institute of Scientific and Technical Information of China (English)

    赵心刚; 韩敬东; 宁元亨; 孟安明; 陈晔光

    2003-01-01

    The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus named as SARS-HCoV.Using bioinformatic methods, we have performed a detailed domain search.In addition to the viral structure proteins, we have found that several putative polypeptides share sequence similarity to known domains or proteins.This study may provide a basis for future studies on the infection and replication process of this notorious virus.

  16. Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

    DEFF Research Database (Denmark)

    Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E;

    2013-01-01

    Background:The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.Methods:We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were...

  17. Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing

    Directory of Open Access Journals (Sweden)

    Nataڑa Vasiljeviš

    2011-01-01

    Full Text Available Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa. We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH samples using the pyrosequencing (PSQ method to identify genes with diagnostic and prognostic potential.

  18. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk

    DEFF Research Database (Denmark)

    Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A;

    2009-01-01

    Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from exis...

  19. Haplotype sharing analysis with SNPs in candidate genes : The genetic analysis workshop 12 example

    NARCIS (Netherlands)

    Fischer, C; Beckmann, L; Majoram, P; Meerman, GT; Chang-Claude, J

    2003-01-01

    Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct

  20. Whole genome amplification of DNA for genotyping pharmacogenetics candidate genes.

    Directory of Open Access Journals (Sweden)

    Santosh ePhilips

    2012-03-01

    Full Text Available Whole genome amplification (WGA technologies can be used to amplify genomic DNA when only small amounts of DNA are available. The Multiple Displacement Amplification Phi polymerase based amplification has been shown to accurately amplify DNA for a variety of genotyping assays; however, it has not been tested for genotyping many of the clinically relevant genes important for pharmacogenetic studies, such as the cytochrome P450 genes, that are typically difficult to genotype due to multiple pseudogenes, copy number variations, and high similarity to other related genes. We evaluated whole genome amplified samples for Taqman™ genotyping of SNPs in a variety of pharmacogenetic genes. In 24 DNA samples from the Coriell human diversity panel, the call rates and concordance between amplified (~200-fold amplification and unamplified samples was 100% for two SNPs in CYP2D6 and one in ESR1. In samples from a breast cancer clinical trial (Trial 1, we compared the genotyping results in samples before and after WGA for four SNPs in CYP2D6, one SNP in CYP2C19, one SNP in CYP19A1, two SNPs in ESR1, and two SNPs in ESR2. The concordance rates were all >97%. Finally, we compared the allele frequencies of 143 SNPs determined in Trial 1 (whole genome amplified DNA to the allele frequencies determined in unamplified DNA samples from a separate trial (Trial 2 that enrolled a similar population. The call rates and allele frequencies between the two trials were 98% and 99.7%, respectively. We conclude that the whole genome amplified DNA is suitable for Taqman™ genotyping for a wide variety of pharmacogenetically relevant SNPs.

  1. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  2. The gut fungus Basidiobolus ranarum has a large genome and different copy numbers of putatively functionally redundant elongation factor genes.

    Directory of Open Access Journals (Sweden)

    Daniel A Henk

    Full Text Available Fungal genomes range in size from 2.3 Mb for the microsporidian Encephalitozoon intestinalis up to 8000 Mb for Entomophaga aulicae, with a mean genome size of 37 Mb. Basidiobolus, a common inhabitant of vertebrate guts, is distantly related to all other fungi, and is unique in possessing both EF-1α and EFL genes. Using DNA sequencing and a quantitative PCR approach, we estimated a haploid genome size for Basidiobolus at 350 Mb. However, based on allelic variation, the nuclear genome is at least diploid, leading us to believe that the final genome size is at least 700 Mb. We also found that EFL was in three times the copy number of its putatively functionally overlapping paralog EF-1α. This suggests that gene or genome duplication may be an important feature of B. ranarum evolution, and also suggests that B. ranarum may have mechanisms in place that favor the preservation of functionally overlapping genes.

  3. The gut fungus Basidiobolus ranarum has a large genome and different copy numbers of putatively functionally redundant elongation factor genes.

    Science.gov (United States)

    Henk, Daniel A; Fisher, Matthew C

    2012-01-01

    Fungal genomes range in size from 2.3 Mb for the microsporidian Encephalitozoon intestinalis up to 8000 Mb for Entomophaga aulicae, with a mean genome size of 37 Mb. Basidiobolus, a common inhabitant of vertebrate guts, is distantly related to all other fungi, and is unique in possessing both EF-1α and EFL genes. Using DNA sequencing and a quantitative PCR approach, we estimated a haploid genome size for Basidiobolus at 350 Mb. However, based on allelic variation, the nuclear genome is at least diploid, leading us to believe that the final genome size is at least 700 Mb. We also found that EFL was in three times the copy number of its putatively functionally overlapping paralog EF-1α. This suggests that gene or genome duplication may be an important feature of B. ranarum evolution, and also suggests that B. ranarum may have mechanisms in place that favor the preservation of functionally overlapping genes. PMID:22363602

  4. Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner; Angquist, Lars; Larsen, Lesli Hingstrup;

    2013-01-01

    after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol, LDL...

  5. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    Directory of Open Access Journals (Sweden)

    Baoman Wang

    2015-01-01

    Full Text Available Apoptosis is the process of programmed cell death (PCD that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature.

  6. Expression of putative zinc-finger protein lcn61 gene in lymphocystis disease virus China (LCDV-cn) genome

    Institute of Scientific and Technical Information of China (English)

    YAN Xiuying; SUN Xiuqin

    2009-01-01

    An open reading frame (lcn61) of iymphocystis disease virus China (LCDV-cn), probably responsible for encoding putative zinc-finger proteins was amplified and inserted into pET24a (+) vector.Then it expressed in E. coli BL21 (DE3), and His-tag fusion protein of high yield was obtained. It was found that the fusion protein existed in E. coli mainly as inclusion bodies. The bioinformatics analysis indicates that LCN61 is C2H2 type zinc-finger protein containing four C2H2 zinc-finger motifs. This work provides a theory for functional research of lcn61 gene.

  7. Candidate driver genes in microsatellite-unstable colorectal cancer

    DEFF Research Database (Denmark)

    Alhopuro, Pia; Sammalkorpi, Heli; Niittymäki, Iina;

    2012-01-01

    . Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6–10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were...... identified in >20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut-off mutation frequencies for repeats of all...

  8. The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components.

    Directory of Open Access Journals (Sweden)

    Peter C Stirling

    2011-04-01

    Full Text Available Chromosome instability (CIN is observed in most solid tumors and is linked to somatic mutations in genome integrity maintenance genes. The spectrum of mutations that cause CIN is only partly known and it is not possible to predict a priori all pathways whose disruption might lead to CIN. To address this issue, we generated a catalogue of CIN genes and pathways by screening ∼ 2,000 reduction-of-function alleles for 90% of essential genes in Saccharomyces cerevisiae. Integrating this with published CIN phenotypes for other yeast genes generated a systematic CIN gene dataset comprised of 692 genes. Enriched gene ontology terms defined cellular CIN pathways that, together with sequence orthologs, created a list of human CIN candidate genes, which we cross-referenced to published somatic mutation databases revealing hundreds of mutated CIN candidate genes. Characterization of some poorly characterized CIN genes revealed short telomeres in mutants of the ASTRA/TTT components TTI1 and ASA1. High-throughput phenotypic profiling links ASA1 to TTT (Tel2-Tti1-Tti2 complex function and to TORC1 signaling via Tor1p stability, consistent with the role of TTT in PI3-kinase related kinase biogenesis. The comprehensive CIN gene list presented here in principle comprises all conserved eukaryotic genome integrity pathways. Deriving human CIN candidate genes from the list allows direct cross-referencing with tumor mutational data and thus candidate mutations potentially driving CIN in tumors. Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease.

  9. Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Ying [Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310009 (China); Wang Youxiang, E-mail: yx_wang@zju.edu.cn [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China); Hu Qiaoling; Shen Jiacong [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China)

    2009-04-30

    The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

  10. Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

    International Nuclear Information System (INIS)

    The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

  11. H2S exposure elicits differential expression of candidate genes in fish adapted to sulfidic and non-sulfidic environments.

    Science.gov (United States)

    Tobler, Michael; Henpita, Chathurika; Bassett, Brandon; Kelley, Joanna L; Shaw, Jennifer H

    2014-09-01

    Disentangling the effects of plasticity, genetic variation, and their interactions on organismal responses to environmental stressors is a key objective in ecological physiology. We quantified the expression of five candidate genes in response to hydrogen sulfide (H2S) exposure in fish (Poecilia mexicana, Poeciliidae) from a naturally sulfide-rich environment as well as an ancestral, non-sulfidic population to test for constitutive and environmentally dependent population differences in gene expression patterns. Common garden raised individuals that had never encountered environmental H2S during their lifetime were subjected to short or long term H2S exposure treatments or respective non-sulfidic controls. The expression of genes involved in responses to H2S toxicity (cytochrome c oxidase, vascular endothelial growth factor, and cytochrome P450-2J6), H2S detoxification (sulfide:quinone oxidoreductase), and endogenous H2S production (cystathionine γ lyase) was determined in both gill and liver tissues by real time PCR. The results indicated complex changes in expression patterns that--depending on the gene--not only differed between organs and populations, but also on the type of H2S exposure. Populations differences, both constitutive and H2S exposure dependent (i.e., plastic), in gene expression were particularly evident for sulfide:quinone oxidoreductase, vascular endothelial growth factor, and to a lesser degree for cytochrome P450-2J6. Our study uncovered putatively adaptive modifications in gene regulation that parallel previously documented adaptive changes in phenotypic traits. PMID:24813672

  12. Acquisition and evolution of plant pathogenesis-associated gene clusters and candidate determinants of tissue-specificity in xanthomonas.

    Directory of Open Access Journals (Sweden)

    Hong Lu

    Full Text Available BACKGROUND: Xanthomonas is a large genus of plant-associated and plant-pathogenic bacteria. Collectively, members cause diseases on over 392 plant species. Individually, they exhibit marked host- and tissue-specificity. The determinants of this specificity are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To assess potential contributions to host- and tissue-specificity, pathogenesis-associated gene clusters were compared across genomes of eight Xanthomonas strains representing vascular or non-vascular pathogens of rice, brassicas, pepper and tomato, and citrus. The gum cluster for extracellular polysaccharide is conserved except for gumN and sequences downstream. The xcs and xps clusters for type II secretion are conserved, except in the rice pathogens, in which xcs is missing. In the otherwise conserved hrp cluster, sequences flanking the core genes for type III secretion vary with respect to insertion sequence element and putative effector gene content. Variation at the rpf (regulation of pathogenicity factors cluster is more pronounced, though genes with established functional relevance are conserved. A cluster for synthesis of lipopolysaccharide varies highly, suggesting multiple horizontal gene transfers and reassortments, but this variation does not correlate with host- or tissue-specificity. Phylogenetic trees based on amino acid alignments of gum, xps, xcs, hrp, and rpf cluster products generally reflect strain phylogeny. However, amino acid residues at four positions correlate with tissue specificity, revealing hpaA and xpsD as candidate determinants. Examination of genome sequences of xanthomonads Xylella fastidiosa and Stenotrophomonas maltophilia revealed that the hrp, gum, and xcs clusters are recent acquisitions in the Xanthomonas lineage. CONCLUSIONS/SIGNIFICANCE: Our results provide insight into the ancestral Xanthomonas genome and indicate that differentiation with respect to host- and tissue-specificity involved not major

  13. Gene Duplication and Gene Expression Changes Play a Role in the Evolution of Candidate Pollen Feeding Genes in Heliconius Butterflies.

    Science.gov (United States)

    Smith, Gilbert; Macias-Muñoz, Aide; Briscoe, Adriana D

    2016-01-01

    Heliconius possess a unique ability among butterflies to feed on pollen. Pollen feeding significantly extends their lifespan, and is thought to have been important to the diversification of the genus. We used RNA sequencing to examine feeding-related gene expression in the mouthparts of four species of Heliconius and one nonpollen feeding species, Eueides isabella We hypothesized that genes involved in morphology and protein metabolism might be upregulated in Heliconius because they have longer proboscides than Eueides, and because pollen contains more protein than nectar. Using de novo transcriptome assemblies, we tested these hypotheses by comparing gene expression in mouthparts against antennae and legs. We first looked for genes upregulated in mouthparts across all five species and discovered several hundred genes, many of which had functional annotations involving metabolism of proteins (cocoonase), lipids, and carbohydrates. We then looked specifically within Heliconius where we found eleven common upregulated genes with roles in morphology (CPR cuticle proteins), behavior (takeout-like), and metabolism (luciferase-like). Closer examination of these candidates revealed that cocoonase underwent several duplications along the lineage leading to heliconiine butterflies, including two Heliconius-specific duplications. Luciferase-like genes also underwent duplication within lepidopterans, and upregulation in Heliconius mouthparts. Reverse-transcription PCR confirmed that three cocoonases, a peptidase, and one luciferase-like gene are expressed in the proboscis with little to no expression in labial palps and salivary glands. Our results suggest pollen feeding, like other dietary specializations, was likely facilitated by adaptive expansions of preexisting genes-and that the butterfly proboscis is involved in digestive enzyme production. PMID:27553646

  14. Transcriptome profiling of khat (Catha edulis and Ephedra sinica reveals gene candidates potentially involved in amphetamine-type alkaloid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Ryan A Groves

    Full Text Available Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis, and include the widely used decongestants and appetite suppressants (1S,2S-pseudoephedrine and (1R,2S-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications.

  15. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  16. Identification of Candidate Genes related to Bovine Marbling using Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Dajeong Lim, Nam-Kuk Kim, Hye-Sun Park, Seung-Hwan Lee, Yong-Min Cho, Sung Jong Oh, Tae-Hun Kim, Heebal Kim

    2011-01-01

    Full Text Available Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The present study systemically analyzed genes associated with bovine marbling score and identified their relationships. The candidate nodes were obtained using MedScan text-mining tools and linked by protein-protein interaction (PPI from the Human Protein Reference Database (HPRD. To determine key node of marbling, the degree and betweenness centrality (BC were used. The hub nodes and biological pathways of our network are consistent with the previous reports about marbling traits, and also suggest unknown candidate genes associated with intramuscular fat. Five nodes were identified as hub genes, which was consistent with the network analysis using quantitative reverse-transcription PCR (qRT-PCR. Key nodes of the PPI network have positive roles (PPARγ, C/EBPα, and RUNX1T1 and negative roles (RXRA, CAMK2A in the development of intramuscular fat by several adipogenesis-related pathways. This study provides genetic information for identifying candidate genes for the marbling trait in bovine.

  17. Mapping a candidate gene (MdMYB10) for red flesh and foliage colour in apple

    Science.gov (United States)

    Chagné, David; Carlisle, Charmaine M; Blond, Céline; Volz, Richard K; Whitworth, Claire J; Oraguzie, Nnadozie C; Crowhurst, Ross N; Allan, Andrew C; Espley, Richard V; Hellens, Roger P; Gardiner, Susan E

    2007-01-01

    Background Integrating plant genomics and classical breeding is a challenge for both plant breeders and molecular biologists. Marker-assisted selection (MAS) is a tool that can be used to accelerate the development of novel apple varieties such as cultivars that have fruit with anthocyanin through to the core. In addition, determining the inheritance of novel alleles, such as the one responsible for red flesh, adds to our understanding of allelic variation. Our goal was to map candidate anthocyanin biosynthetic and regulatory genes in a population segregating for the red flesh phenotypes. Results We have identified the Rni locus, a major genetic determinant of the red foliage and red colour in the core of apple fruit. In a population segregating for the red flesh and foliage phenotype we have determined the inheritance of the Rni locus and DNA polymorphisms of candidate anthocyanin biosynthetic and regulatory genes. Simple Sequence Repeats (SSRs) and Single Nucleotide Polymorphisms (SNPs) in the candidate genes were also located on an apple genetic map. We have shown that the MdMYB10 gene co-segregates with the Rni locus and is on Linkage Group (LG) 09 of the apple genome. Conclusion We have performed candidate gene mapping in a fruit tree crop and have provided genetic evidence that red colouration in the fruit core as well as red foliage are both controlled by a single locus named Rni. We have shown that the transcription factor MdMYB10 may be the gene underlying Rni as there were no recombinants between the marker for this gene and the red phenotype in a population of 516 individuals. Associating markers derived from candidate genes with a desirable phenotypic trait has demonstrated the application of genomic tools in a breeding programme of a horticultural crop species. PMID:17608951

  18. Mapping a candidate gene (MdMYB10 for red flesh and foliage colour in apple

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2007-07-01

    Full Text Available Abstract Background Integrating plant genomics and classical breeding is a challenge for both plant breeders and molecular biologists. Marker-assisted selection (MAS is a tool that can be used to accelerate the development of novel apple varieties such as cultivars that have fruit with anthocyanin through to the core. In addition, determining the inheritance of novel alleles, such as the one responsible for red flesh, adds to our understanding of allelic variation. Our goal was to map candidate anthocyanin biosynthetic and regulatory genes in a population segregating for the red flesh phenotypes. Results We have identified the Rni locus, a major genetic determinant of the red foliage and red colour in the core of apple fruit. In a population segregating for the red flesh and foliage phenotype we have determined the inheritance of the Rni locus and DNA polymorphisms of candidate anthocyanin biosynthetic and regulatory genes. Simple Sequence Repeats (SSRs and Single Nucleotide Polymorphisms (SNPs in the candidate genes were also located on an apple genetic map. We have shown that the MdMYB10 gene co-segregates with the Rni locus and is on Linkage Group (LG 09 of the apple genome. Conclusion We have performed candidate gene mapping in a fruit tree crop and have provided genetic evidence that red colouration in the fruit core as well as red foliage are both controlled by a single locus named Rni. We have shown that the transcription factor MdMYB10 may be the gene underlying Rni as there were no recombinants between the marker for this gene and the red phenotype in a population of 516 individuals. Associating markers derived from candidate genes with a desirable phenotypic trait has demonstrated the application of genomic tools in a breeding programme of a horticultural crop species.

  19. Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI

    Science.gov (United States)

    Vimaleswaran, Karani S.; Tachmazidou, Ioanna; Zhao, Jing Hua; Hirschhorn, Joel N.; Dudbridge, Frank; Loos, Ruth J.F.

    2012-01-01

    Before the advent of genome-wide association studies (GWASs), hundreds of candidate genes for obesity-susceptibility had been identified through a variety of approaches. We examined whether those obesity candidate genes are enriched for associations with body mass index (BMI) compared with non-candidate genes by using data from a large-scale GWAS. A thorough literature search identified 547 candidate genes for obesity-susceptibility based on evidence from animal studies, Mendelian syndromes, linkage studies, genetic association studies and expression studies. Genomic regions were defined to include the genes ±10 kb of flanking sequence around candidate and non-candidate genes. We used summary statistics publicly available from the discovery stage of the genome-wide meta-analysis for BMI performed by the genetic investigation of anthropometric traits consortium in 123 564 individuals. Hypergeometric, rank tail-strength and gene-set enrichment analysis tests were used to test for the enrichment of association in candidate compared with non-candidate genes. The hypergeometric test of enrichment was not significant at the 5% P-value quantile (P = 0.35), but was nominally significant at the 25% quantile (P = 0.015). The rank tail-strength and gene-set enrichment tests were nominally significant for the full set of genes and borderline significant for the subset without SNPs at P < 10−7. Taken together, the observed evidence for enrichment suggests that the candidate gene approach retains some value. However, the degree of enrichment is small despite the extensive number of candidate genes and the large sample size. Studies that focus on candidate genes have only slightly increased chances of detecting associations, and are likely to miss many true effects in non-candidate genes, at least for obesity-related traits. PMID:22791748

  20. Social cognitive role of schizophrenia candidate gene GABRB2.

    Directory of Open Access Journals (Sweden)

    Shui Ying Tsang

    Full Text Available The occurrence of positive selection in schizophrenia-associated GABRB2 suggests a broader impact of the gene product on population fitness. The present study considered the possibility of cognition-related GABRB2 involvement by examining the association of GABRB2 with psychosis and altruism, respectively representing psychiatric and psychological facets of social cognition. Four single nucleotide polymorphisms (SNPs were genotyped for quantitative trait analyses and population-based association studies. Psychosis was measured by either the Positive and Negative Syndrome Scale (PANSS or antipsychotics dosage, and altruism was based on a self-report altruism scale. The minor alleles of SNPs rs6556547, rs1816071 and rs187269 in GABRB2 were correlated with high PANSS score for positive symptoms in a Han Chinese schizophrenic cohort, whereas those of rs1816071 and rs1816072 were associated with high antipsychotics dosage in a US Caucasian schizophrenic cohort. Moreover, strongly significant GABRB2-disease associations were found among schizophrenics with severe psychosis based on high PANSS positive score, but no significant association was observed for schizophrenics with only mild psychosis. Interestingly, in addition to association with psychosis in schizophrenics, rs187269 was also associated with altruism in healthy Han Chinese. Furthermore, parallel to correlation with severe psychosis, its minor allele was correlated with high altruism scores. These findings revealed that GABRB2 is associated with psychosis, the core symptom and an endophenotype of schizophrenia. Importantly, the association was found across the breadth of the psychiatric (psychosis to psychological (altruism spectrum of social cognition suggesting GABRB2 involvement in human cognition.

  1. De Novo Transcriptome Assembly in Shiraia bambusicola to Investigate Putative Genes Involved in the Biosynthesis of Hypocrellin A.

    Science.gov (United States)

    Zhao, Ning; Lin, Xi; Qi, Shan-Shan; Luo, Zhi-Mei; Chen, Shuang-Lin; Yan, Shu-Zhen

    2016-01-01

    Shiraia bambusicola is a species of the monotypic genus Shiraia in the phylum Ascomycota. In China, it is known for its pharmacological properties that are used to treat rheumatic arthritis, sciatica, pertussis, tracheitis and so forth. Its major medicinal active metabolite is hypocrellin A, which exhibits excellent antiviral and antitumor properties. However, the genes involved in the hypocrellin A anabolic pathways were still unknown due to the lack of genomic information for this species. To investigate putative genes that are involved in the biosynthesis of hypocrellin A and determine the pathway, we performed transcriptome sequencing for Shiraia bambusicola S4201-W and the mutant S4201-D1 for the first time. S4201-W has excellent hypocrellin A production, while the mutant S4201-D1 does not. Then, we obtained 38,056,034 and 39,086,896 clean reads from S4201-W and S4201-D1, respectively. In all, 17,923 unigenes were de novo assembled, and the N50 length was 1970 bp. Based on the negative binomial distribution test, 716 unigenes were found to be upregulated, and 188 genes were downregulated in S4201-D1, compared with S4201-W. We have found seven unigenes involved in the biosynthesis of hypocrellin A and proposed a putative hypocrellin A biosynthetic pathway. These data will provide a valuable resource and theoretical basis for future molecular studies of hypocrellin A, help identify the genes involved in the biosynthesis of hypocrellin A and help facilitate functional studies for enhancing hypocrellin A production. PMID:26927096

  2. Characterization of five putative aspartate aminotransferase genes in the N2-fixing heterocystous cyanobacterium Anabaena sp. strain PCC 7120.

    Science.gov (United States)

    Xu, Xinyi; Gu, Liping; He, Ping; Zhou, Ruanbao

    2015-06-01

    Aspartate and glutamate are two key amino acids used in biosynthesis of many amino acids that play vital role in cellular metabolism. Aspartate aminotransferases (AspATs) are required for channelling nitrogen (N(2)) between Glu and Asp in all life forms. Biochemical and genetic characterization of AspATs have been lacking in N(2)-fixing cyanobacteria. In this report, five putative AspAT genes (alr1039, all2340, alr2765, all4327 and alr4853) were identified in the N(2)-fixing heterocystous cyanobacterium Anabaena sp. PCC 7120. Five recombinant C-terminal hexahistidine-tagged AspATs (AspAT-H(6)) were overexpressed in Escherichia coli and purified to homogeneity. Biochemical analysis demonstrated that these five putative AspATs have authentic AspAT activity in vitro using aspartate as an amino donor. However, the enzymic activities of the five AspATs differed in vitro. Alr4853-H(6) showed the highest AspAT activity, while the enzymic activity for the other four AspATs ranged from 6.5 to 53.7 % activity compared to Alr4853 (100 %). Genetic characterization of the five AspAT genes was also performed by inactivating each individual gene. All of the five AspAT knockout mutants exhibited reduced diazotrophic growth, and alr4853 was further identified to be a Fox gene (requiring fixed N(2) for growth in the presence of oxygen). Four out of five P(aspAT)-gfp transcriptional fusions were constitutively expressed in both diazotrophic and nitrate-dependent growth conditions. Quantitative reverse transcriptase PCR showed that alr4853 expression was increased by 2.3-fold after 24 h of N(2) deprivation. Taken together, these findings add to our understanding of the role of AspATs in N(2)-fixing within heterocystous cyanobacteria.

  3. Mouse autosomal homolog of DAZ, a candidate male sterility gene in humans, is expressed in male germ cells before and after puberty

    Energy Technology Data Exchange (ETDEWEB)

    Reijo, R.; Seligman, J.; Jaffe, T. [Massachusetts Institute of Technology, Cambridge, MA (United States)] [and others

    1996-07-15

    Deletion of the Azoospermia Factor (AZF) region of the human Y chromosome results in spermatogenic failure. While the identity of the critical missing gene has yet to be established, a strong candidate is the putative RNA-binding protein DAZ (Deleted in Azoospermia). Here we describe the mouse homolog of DAZ. Unlike human DAZ, which is Y-linked, in mouse the Dazh (DAZ homolog) gene maps to chromosome 17. Nonetheless, the predicted amino acid sequences of the gene products are quite similar, especially in their RNP/RRM (putative RNA-binding) domains, and both genes are transcribed predominantly in testes; the mouse gene is transcribed at a lower level in ovaries. Dazh transcripts were not detected in testes of mice that lack germ cells. In testes of wildtype mice, Dazh transcription is detectable 1 day after birth (when the only germ cells are prospermatogonia), increases steadily as spermatogonial stem cells appear, plateaus as the first wave of spermatogenic cells enters meiosis (10 days after birth), and is sustained at this level thereafter. This unique pattern of expression suggests the Dazh participates in differentiation, proliferation, or maintenance of germ cell founder populations before, during, and after the pubertal onset of spermatogenesis. Such functions could readily account for the diverse spermatogenic defects observed in human males with AZF deletion. 29 refs., 4 figs.

  4. Third chromosome candidate genes for conspecific sperm precedence between D. simulans and D. mauritiana

    Directory of Open Access Journals (Sweden)

    Brouwers Barb

    2010-04-01

    Full Text Available Abstract Background Male - female incompatibilities can be critical in keeping species as separate and discrete units. Premating incompatibilities and postzygotic hybrid sterility/inviability have been widely studied as isolating barriers between species. In recent years, a number of studies have brought attention to postmating prezygotic barriers arising from male - male competition and male - female interactions. Yet little is known about the genetic basis of postmating prezygotic isolation barriers between species. Results Using D. simulans lines with mapped introgressions of D. mauritiana into their third chromosome, we find at least two D. mauritiana introgressions causing male breakdown in competitive paternity success. Eighty one genes within the mapped introgressed regions were identified as broad-sense candidates on the basis of male reproductive tract expression and male-related function. The list of candidates was narrowed down to five genes based on differences in male reproductive tract expression between D. simulans and D. mauritiana. Another ten genes were confirmed as candidates using evidence of adaptive gene coding sequence diversification in the D. simulans and/or D. mauritiana lineage. Our results show a complex genetic basis for conspecific sperm precedence, with evidence of gene interactions between at least two third chromosome loci. Pleiotropy is also evident from correlation between conspecific sperm precedence and female induced fecundity and the identification of candidate genes that might exert an effect through genetic conflict and immunity. Conclusions We identified at least two loci responsible for conspecific sperm precedence. A third of candidate genes within these two loci are located in the 89B cytogenetic position, highlighting a possible major role for this chromosome position during the evolution of species specific adaptations to postmating prezygotic reproductive challenges.

  5. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    Science.gov (United States)

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

  6. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    Science.gov (United States)

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies. PMID:24736736

  7. Integrated Metabolo-Transcriptomics Reveals Fusarium Head Blight Candidate Resistance Genes in Wheat QTL-Fhb2

    Science.gov (United States)

    Dhokane, Dhananjay; Karre, Shailesh; Kushalappa, Ajjamada C.; McCartney, Curt

    2016-01-01

    Background Fusarium head blight (FHB) caused by Fusarium graminearum not only causes severe losses in yield, but also reduces quality of wheat grain by accumulating mycotoxins. Breeding for host plant resistance is considered as the best strategy to manage FHB. Resistance in wheat to FHB is quantitative in nature, involving cumulative effects of many genes governing resistance. The poor understanding of genetics and lack of precise phenotyping has hindered the development of FHB resistant cultivars. Though more than 100 QTLs imparting FHB resistance have been reported, none discovered the specific genes localized within the QTL region, nor the underlying mechanisms of resistance. Findings In our study recombinant inbred lines (RILs) carrying resistant (R-RIL) and susceptible (S-RIL) alleles of QTL-Fhb2 were subjected to metabolome and transcriptome profiling to discover the candidate genes. Metabolome profiling detected a higher abundance of metabolites belonging to phenylpropanoid, lignin, glycerophospholipid, flavonoid, fatty acid, and terpenoid biosynthetic pathways in R-RIL than in S-RIL. Transcriptome analysis revealed up-regulation of several receptor kinases, transcription factors, signaling, mycotoxin detoxification and resistance related genes. The dissection of QTL-Fhb2 using flanking marker sequences, integrating metabolomic and transcriptomic datasets, identified 4-Coumarate: CoA ligase (4CL), callose synthase (CS), basic Helix Loop Helix (bHLH041) transcription factor, glutathione S-transferase (GST), ABC transporter-4 (ABC4) and cinnamyl alcohol dehydrogenase (CAD) as putative resistance genes localized within the QTL-Fhb2 region. Conclusion Some of the identified genes within the QTL region are associated with structural resistance through cell wall reinforcement, reducing the spread of pathogen through rachis within a spike and few other genes that detoxify DON, the virulence factor, thus eventually reducing disease severity. In conclusion, we

  8. Differential expression of putative drug resistance genes in Mycobacterium tuberculosis clinical isolates.

    Science.gov (United States)

    González-Escalante, Laura; Peñuelas-Urquides, Katia; Said-Fernández, Salvador; Silva-Ramírez, Beatriz; Bermúdez de León, Mario

    2015-12-01

    Understanding drug resistance in Mycobacterium tuberculosis requires an integrated analysis of strain lineages, mutations and gene expression. Previously, we reported the differential expression of esxG, esxH, infA, groES, rpmI, rpsA and lipF genes in a sensitive M. tuberculosis strain and in a multidrug-resistant clinical isolate. Here, we have evaluated the expression of these genes in 24 clinical isolates that belong to different lineages and have different drug resistance profiles. In vitro, growth kinetics analysis showed no difference in the growth of the clinical isolates, and thus drug resistance occurred without a fitness cost. However, a quantitative reverse transcription PCR analysis of gene expression revealed high variability among the clinical isolates, including those with similar drug resistance profiles. Due to the complexity of gene regulation pathways and the wide diversity of M. tuberculosis lineages, the use of gene expression as a molecular signature for drug resistance is not straightforward. Therefore, we recommend that the expression of M. tuberculosis genes be performed individually, and baseline expression levels should be verified among several different clinical isolates, before any further applications of these findings.

  9. Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer

    OpenAIRE

    Burghel, George J.; Wei-Yu Lin; Helen Whitehouse; Ian Brock; David Hammond; Jonathan Bury; Yvonne Stephenson; Rina George; Angela Cox

    2013-01-01

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hy...

  10. Candidate gene study to investigate the genetic determinants of normal variation in central corneal thickness

    OpenAIRE

    Dimasi, David P.; Kathryn P Burdon; Hewitt, Alex W; Savarirayan, Ravi; Healey, Paul R.; Mitchell, Paul; Mackey, David A.; Craig, Jamie E

    2010-01-01

    Purpose The genetic component underlying variation in central corneal thickness (CCT) in the normal population remains largely unknown. As CCT is an identified risk factor for open-angle glaucoma, understanding the genes involved in CCT determination could improve our understanding of the mechanisms involved in this association. Methods To identify novel CCT genes, we selected eight different candidates based on a range of criteria. These included; aquaporin 1 (AQ1), aquaporin 5 (AQ5), decori...

  11. Physiological and molecular characterization of drought responses and identification of candidate tolerance genes in cassava

    OpenAIRE

    Turyagyenda, Laban F.; Kizito, Elizabeth B.; Ferguson, Morag; Baguma, Yona; Agaba, Morris; Jagger J W Harvey; Osiru, David S. O.

    2013-01-01

    Cassava is an important root crop to resource-poor farmers in marginal areas, where its production faces drought stress constraints. Given the difficulties associated with cassava breeding, a molecular understanding of drought tolerance in cassava will help in the identification of markers for use in marker-assisted selection and genes for transgenic improvement of drought tolerance. This study was carried out to identify candidate drought-tolerance genes and expression-based markers of droug...

  12. Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, L.; Ballabio, A.; Zoghbi, H.Y. [Baylor College of Medicine, Houston, TX (United States)

    1996-06-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder associated with X chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include microphthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. Using a cross-species conservation strategy, an expressed sequence from the 450- to the 550-kb MLS critical region on Xp22 was identified by screening a human embryo cDNA library. Northern analysis revealed a transcript of {approx}2.6 kb in all tissues examined, with weaker expression of {approx}1.2- and {approx}5.2-kb transcripts. The strongest expression was observed in heart and skeletal muscle. Sequence analysis of a 3-kb cDNA contig revealed an 807-bp open reading frame encoding a putative 268-amino-acid-protein. Comparison of the sequence with sequences in the databases revealed homology with holocytochrome c-type synthetases, which catalyze the covalent addition of a heme group onto c-type cytochromes in the mitochondria. The c-type cytochromes are required for proper functioning of the electron transport pathway. The human gene (HGMW-approved symbol HCCS) and the corresponding murine gene characterized in this paper are the first mammalian holocytochrome c-type synthetases to be described in the literature. Because of the lack of a neuromuscular phenotype in MLS, it is uncertain whether the deletion of a mitochondrial holocytochrome synthetase would contribute to the phenotype seen in MLS. The expression pattern of this gene and knowledge about the function of holocytochrome synthetases, however, suggest that it is a good candidate for X-linked encephalomyopathies typically associated with mitochondrial dysfunction. 25 refs., 4 figs.

  13. Functional annotation and identification of candidate disease genes by computational analysis of normal tissue gene expression data.

    Directory of Open Access Journals (Sweden)

    Laura Miozzi

    Full Text Available BACKGROUND: High-throughput gene expression data can predict gene function through the "guilt by association" principle: coexpressed genes are likely to be functionally associated. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed publicly available expression data on normal human tissues. The analysis is based on the integration of data obtained with two experimental platforms (microarrays and SAGE and of various measures of dissimilarity between expression profiles. The building blocks of the procedure are the Ranked Coexpression Groups (RCG, small sets of tightly coexpressed genes which are analyzed in terms of functional annotation. Functionally characterized RCGs are selected by means of the majority rule and used to predict new functional annotations. Functionally characterized RCGs are enriched in groups of genes associated to similar phenotypes. We exploit this fact to find new candidate disease genes for many OMIM phenotypes of unknown molecular origin. CONCLUSIONS/SIGNIFICANCE: We predict new functional annotations for many human genes, showing that the integration of different data sets and coexpression measures significantly improves the scope of the results. Combining gene expression data, functional annotation and known phenotype-gene associations we provide candidate genes for several genetic diseases of unknown molecular basis.

  14. Identification of candidate olfactory genes in Leptinotarsa decemlineata by antennal transcriptome analysis

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-06-01

    Full Text Available The sense of smell is critical for the survival of insects, by which insects detect the odor signals in the environment and make appropriate behavioral responses such as host preference, mate choice, and oviposition site selection. The antenna is the main olfactory organ in insects. Multiple antennal proteins have been suggested to be involved in olfactory signal transduction pathway such as odorant receptors (ORs, ionotropic receptors (IRs, odorant binding proteins (OBPs, chemosensory proteins (CSPs and sensory neuron membrane proteins (SNMPs. In this study, we identified several olfactory gene subfamilies in the economically important Coleopteran agricultural pest, Leptinotarsa decemlineata, by assembling the adult male and female antennal transcriptomes. In the male and female antennal transcriptome, we identified a total of 37 OR genes, 10 IR genes, 26 OBP genes, 15 CSP genes and 3 SNMP genes. Further all candidate ORs were validated to be expressed in male or female antenna by semi-quantitative reverse transcription PCR. Most of the candidate OR genes have similar expression level in male and female. A few OR genes have been detected as male-specific (LdecOR6 or male-bias (LdecOR5, LdecOR12, LdecOR26 and LdecOR32 expression. As well as that, two OR genes (LdecOR3 and LdecOR29 were proved to be expressed higher in female. Our findings make it possible for future research of the olfactory system of L. decemlineata at the molecular level.

  15. Molecular evolution of candidate genes for crop-related traits in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Mandel, Jennifer R; McAssey, Edward V; Nambeesan, Savithri; Garcia-Navarro, Elena; Burke, John M

    2014-01-01

    Evolutionary analyses aimed at detecting the molecular signature of selection during crop domestication and/or improvement can be used to identify genes or genomic regions of likely agronomic importance. Here, we describe the DNA sequence-based characterization of a pool of candidate genes for crop-related traits in sunflower. These genes, which were identified based on homology to genes of known effect in other study systems, were initially sequenced from a panel of improved lines. All genes that exhibited a paucity of sequence diversity, consistent with the possible effects of selection during the evolution of cultivated sunflower, were then sequenced from a panel of wild sunflower accessions an outgroup. These data enabled formal tests for the effects of selection in shaping sequence diversity at these loci. When selection was detected, we further sequenced these genes from a panel of primitive landraces, thereby allowing us to investigate the likely timing of selection (i.e., domestication vs. improvement). We ultimately identified seven genes that exhibited the signature of positive selection during either domestication or improvement. Genetic mapping of a subset of these genes revealed co-localization between candidates for genes involved in the determination of flowering time, seed germination, plant growth/development, and branching and QTL that were previously identified for these traits in cultivated × wild sunflower mapping populations. PMID:24914686

  16. Molecular evolution of candidate genes for crop-related traits in sunflower (Helianthus annuus L..

    Directory of Open Access Journals (Sweden)

    Jennifer R Mandel

    Full Text Available Evolutionary analyses aimed at detecting the molecular signature of selection during crop domestication and/or improvement can be used to identify genes or genomic regions of likely agronomic importance. Here, we describe the DNA sequence-based characterization of a pool of candidate genes for crop-related traits in sunflower. These genes, which were identified based on homology to genes of known effect in other study systems, were initially sequenced from a panel of improved lines. All genes that exhibited a paucity of sequence diversity, consistent with the possible effects of selection during the evolution of cultivated sunflower, were then sequenced from a panel of wild sunflower accessions an outgroup. These data enabled formal tests for the effects of selection in shaping sequence diversity at these loci. When selection was detected, we further sequenced these genes from a panel of primitive landraces, thereby allowing us to investigate the likely timing of selection (i.e., domestication vs. improvement. We ultimately identified seven genes that exhibited the signature of positive selection during either domestication or improvement. Genetic mapping of a subset of these genes revealed co-localization between candidates for genes involved in the determination of flowering time, seed germination, plant growth/development, and branching and QTL that were previously identified for these traits in cultivated × wild sunflower mapping populations.

  17. A putative gene cluster from a Lyngbya wollei bloom that encodes paralytic shellfish toxin biosynthesis.

    Directory of Open Access Journals (Sweden)

    Troco K Mihali

    Full Text Available Saxitoxin and its analogs cause the paralytic shellfish-poisoning syndrome, adversely affecting human health and coastal shellfish industries worldwide. Here we report the isolation, sequencing, annotation, and predicted pathway of the saxitoxin biosynthetic gene cluster in the cyanobacterium Lyngbya wollei. The gene cluster spans 36 kb and encodes enzymes for the biosynthesis and export of the toxins. The Lyngbya wollei saxitoxin gene cluster differs from previously identified saxitoxin clusters as it contains genes that are unique to this cluster, whereby the carbamoyltransferase is truncated and replaced by an acyltransferase, explaining the unique toxin profile presented by Lyngbya wollei. These findings will enable the creation of toxin probes, for water monitoring purposes, as well as proof-of-concept for the combinatorial biosynthesis of these natural occurring alkaloids for the production of novel, biologically active compounds.

  18. Cloning and expression of putative ethylene receptor genes in soybean plant

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ethylene plays important roles in plant growth, development, and stress responses, and ethylene receptors have been identified and studied extensively in various plant species. Here we report the cloning of four ethylene receptor genes from soybean, i.e.GmETR1, GmERS1, GmETR2 and GmEIN4. Construction of the phylogenic tree showed that GmETR1 and GmERS1 belong to subfamily Ⅰ whereas GmETR2 and GmEIN4 belong to subfamily Ⅱ. The four ethylene receptor genes showed different tissue-specific expression patterns in roots, stems, leaves, cotyledons, flowers, pods and seeds of soybean. These genes were differentially regulated by various abiotic stresses and plant hormones. The possible roles of the four genes in soybean plant were also discussed.

  19. Genetics of Estrogen-Related Traits; From Candidate Genes to GWAS

    NARCIS (Netherlands)

    L. Stolk (Lisette)

    2009-01-01

    textabstractIn the first part of this thesis, the association of polymorphisms in three candidate genes (estrogen receptor alpha (ESR1), retinoblastoma interacting zinc finger domain (RIZ1) and catechol-O-methyltransferase (COMT)) with estradiol levels, age at natural menopause, BMD and fracture ris

  20. Identification of candidate driver genes in common focal chromosomal aberrations of microsatellite stable colorectal cancer.

    Directory of Open Access Journals (Sweden)

    George J Burghel

    Full Text Available Colorectal cancer (CRC is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN is a major driving force of microsatellite stable (MSS sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR at high frequency (>10%. Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains. Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver genes.

  1. Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer

    Science.gov (United States)

    Burghel, George J.; Lin, Wei-Yu; Whitehouse, Helen; Brock, Ian; Hammond, David; Bury, Jonathan; Stephenson, Yvonne; George, Rina; Cox, Angela

    2013-01-01

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver genes. PMID:24367615

  2. Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene;

    2011-01-01

    Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein...

  3. Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients

    DEFF Research Database (Denmark)

    de Kovel, Carolien G F; Brilstra, Eva H; van Kempen, Marjan J A;

    2016-01-01

    BACKGROUND: Many genes are candidates for involvement in epileptic encephalopathy (EE) because one or a few possibly pathogenic variants have been found in patients, but insufficient genetic or functional evidence exists for a definite annotation. METHODS: To increase the number of validated EE...

  4. No association of candidate genes with cannabis use in a large sample of Australian twin families

    NARCIS (Netherlands)

    Verweij, C.J.H.; Zietsch, B.P.; Liu, J.Z.; Medland, S.E.; Lynskey, M.T.; Madden, P.A.F.; Agrawal, A.; Montgomery, G.W.; Heath, A.C.; Martin, N.G.

    2012-01-01

    While there is solid evidence that cannabis use is heritable, attempts to identify genetic influences at the molecular level have yielded mixed results. Here, a large twin family sample (n = 7452) was used to test for association between 10 previously reported candidate genes and lifetime frequency

  5. Cloning and Expression Pattern of a Gene Encoding a Putative Plastidic ATP/ADP Transporter from Helianthus tuberosus L.

    Institute of Scientific and Technical Information of China (English)

    Kun MENG; Tuan-Jie CHANG; Xiang LIU; Song-Biao CHEN; Yong-Qin WANG; Ai-Jun SUN; Hong-Lin XU; Xiao-Li WEI; Zhen ZHU

    2005-01-01

    Herein, we report the cloning and molecular characterization of a full cDNA encoding a putative plastidic ATP/ADP transporter, designated HtAATP, for Helianthus tuberosus L. The ATP/ADP translocator protein was isolated from the tuber-cDNA library of H. tuberosus for the first time. The predicted HtAATP protein was judged as a plastidic ATP/ADP translocator protein from its high homology at the amino acid sequence level to the two Arabidopsis thaliana plastidic ATP/ADP translocator proteins AATP1 and AATP2 (84.8% and 79.9% identity, respectively). Amino acid sequence analysis of the primary structure of HtAATP revealed that it belonged to the plastidic ATP/ADP transporter family. Hydropathy prediction indicated that HtAATP gene product is a highly hydrophobic membrane protein that contains 10 transmembrane domains to form a spanning topology. Southern blotting analysis showed that the HtAATP gene is a single-copy gene in the H. tuberosus genome. Tissue distribution analysis showed that the HtAATP gene is prominently expressed in sink tissues. A stable expression pattern in tubers at different developmental stages implies an active involvement of HtAATP during carbohydrate formation.

  6. Characterization of Bois noir isolates by restriction fragment length polymorphism of a Stolbur-specific putative membrane protein gene.

    Science.gov (United States)

    Pacifico, D; Alma, A; Bagnoli, B; Foissac, X; Pasquini, G; Tessitori, M; Marzachì, C

    2009-06-01

    Bois noir phytoplasma (BNp), widespread in wine-producing areas of Europe and endemic in France and Italy, is classified in the 16SrXII-A subgroup, whose members are referred to as Stolbur phytoplasmas. The 16S rDNA gene of Stolbur phytoplasma shows low variability, and few non-ribosomal genes are available as markers to assess variation among isolates. We used the Stolbur-specific stol-1H10 gene, encoding a putative membrane-exposed protein, to investigate genetic diversity of French and Italian BNp isolates from plants and insects. Amplification of stol-1H10 from infected grapevines, weeds, and Hyalesthes obsoletus produced fragments of three sizes, and restriction fragment length polymorphism analysis divided these amplicons further into 12 profiles (V1 to V12). French BNp isolates were more variable than Italian ones, and different profiles were present in infected grapevines from France and Italy. Isolate V3, most abundant among Italian affected grapes but present among French ones, was found in one Urtica dioica sample and in all H. obsoletus collected on this species. Four Italian-specific profiles were represented among infected Convolvulus arvensis, the most frequent of which (V12) was also detected in H. obsoletus collected on this species. Most of the variability in the stol-1H10 sequence was associated with type II on the tuf gene. PMID:19453230

  7. Cladosporium cladosporioides LPSC 1088 produces the 1,8-dihydroxynaphthalene-melanin-like compound and carries a putative pks gene.

    Science.gov (United States)

    Llorente, Carla; Bárcena, Alejandra; Vera Bahima, José; Saparrat, Mario C N; Arambarri, Angélica M; Rozas, M Fernanda; Mirífico, María V; Balatti, Pedro A

    2012-12-01

    Cladosporium cladosporioides is a dematiaceous fungus with coloured mycelia and conidia due to the presence of dark pigments. The purpose of this study was to characterize the dark pigments synthetized by Cladosporium sp. LPSC no. 1088 and also to identify the putative polyketide synthase (pks) gene that might be involved in the pigment biosynthesis. Morphological as well as molecular features like the ITS sequence confirmed that LPSC 1088 is Cladosporium cladosporioides. UV-visible, Fourier Transform Infrared (FTIR) and Electron Spin Resonance (ESR) spectroscopy analysis as well as melanin inhibitors suggest that the main dark pigment of the isolate was 1,8 dihydroxynaphthalene (DHN)-melanin-type compound. Two commercial fungicides, Difenoconazole and Chlorothalonil, inhibited fungal growth as well as increased pigmentation of the colonies suggesting that melanin might protect the fungus against chemical stress. The pigment is most probably synthetized by means of a pentaketide pathway since the sequence of a 651 bp fragment, coding for a putative polyketide synthase, is highly homologous to pks sequences from other fungi.

  8. Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

    Directory of Open Access Journals (Sweden)

    Xuefeng Ren

    Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

  9. Cloning and characterization of two putative seven-transmembrane receptor genes from cotton

    Institute of Scientific and Technical Information of China (English)

    Peng Gao; Piming Zhao; Juan Wang; Haiyun Wang; Guiling Wang; Guixian Xia

    2008-01-01

    Using rapid amplification of cDNA ends (RACE)-PCR,two full-length cDNAs encoding putative seven-transmembrane receptors (designated Gh7TMpR1 and Gh7TMpR2) were cloned from cotton plants.Southern blot and an ApaLl restriction site polymorphism analyses revealed that GhTTMpR1 was derived from the ancestral A diploid genome,while Gh7TMpR2 was from the D subgenome.Northern blot hybridization indicated that both Gh7TMpR1 and Gh7TMpR2 were expressed preferentially in the elongation phase of fiber development.Majority of the Gh7TMpR1 proteins were located within the membrane structure and displayed a punctuate pattern of distribution.Overexpression of Gh7TMpR1 in fission yeast disrupted the polar growth and caused the formation of rounded cells.These results suggest that GhT7MpRI may play a critical role in cotton fiber development,perhaps as a signaling receptor that is involved in controlling fiber elongation.

  10. Targeted Sequencing Reveals Large-Scale Sequence Polymorphism in Maize Candidate Genes for Biomass Production and Composition.

    Directory of Open Access Journals (Sweden)

    Moses M Muraya

    Full Text Available A major goal of maize genomic research is to identify sequence polymorphisms responsible for phenotypic variation in traits of economic importance. Large-scale detection of sequence variation is critical for linking genes, or genomic regions, to phenotypes. However, due to its size and complexity, it remains expensive to generate whole genome sequences of sufficient coverage for divergent maize lines, even with access to next generation sequencing (NGS technology. Because methods involving reduction of genome complexity, such as genotyping-by-sequencing (GBS, assess only a limited fraction of sequence variation, targeted sequencing of selected genomic loci offers an attractive alternative. We therefore designed a sequence capture assay to target 29 Mb genomic regions and surveyed a total of 4,648 genes possibly affecting biomass production in 21 diverse inbred maize lines (7 flints, 14 dents. Captured and enriched genomic DNA was sequenced using the 454 NGS platform to 19.6-fold average depth coverage, and a broad evaluation of read alignment and variant calling methods was performed to select optimal procedures for variant discovery. Sequence alignment with the B73 reference and de novo assembly identified 383,145 putative single nucleotide polymorphisms (SNPs, of which 42,685 were non-synonymous alterations and 7,139 caused frameshifts. Presence/absence variation (PAV of genes was also detected. We found that substantial sequence variation exists among genomic regions targeted in this study, which was particularly evident within coding regions. This diversification has the potential to broaden functional diversity and generate phenotypic variation that may lead to new adaptations and the modification of important agronomic traits. Further, annotated SNPs identified here will serve as useful genetic tools and as candidates in searches for phenotype-altering DNA variation. In summary, we demonstrated that sequencing of captured DNA is a powerful

  11. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder.

    Science.gov (United States)

    Ashbrook, David G; Williams, Robert W; Lu, Lu; Hager, Reinmar

    2015-01-01

    Bipolar disorder (BD) is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS) have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium's bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis. We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1, and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG, and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG, and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG, and TNR influence intercellular signaling in the striatum. PMID:26190982

  12. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  13. Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Jinling Wang

    2014-09-01

    Full Text Available Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

  14. Association analysis of frost tolerance in rye using candidate genes and phenotypic data from controlled, semi-controlled, and field phenotyping platforms

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    Li Yongle

    2011-10-01

    Full Text Available Abstract Background Frost is an important abiotic stress that limits cereal production in the temperate zone. As the most frost tolerant small grain cereal, rye (Secale cereale L. is an ideal cereal model for investigating the genetic basis of frost tolerance (FT, a complex trait with polygenic inheritance. Using 201 genotypes from five Eastern and Middle European winter rye populations, this study reports a multi-platform candidate gene-based association analysis in rye using 161 single nucleotide polymorphisms (SNPs and nine insertion-deletion (Indel polymorphisms previously identified from twelve candidate genes with a putative role in the frost responsive network. Results Phenotypic data analyses of FT in three different phenotyping platforms, controlled, semi-controlled and field, revealed significant genetic variations in the plant material under study. Statistically significant (P ScCbf15 and one in ScCbf12, all leading to amino acid exchanges, were significantly associated with FT over all three phenotyping platforms. Distribution of SNP effect sizes expressed as percentage of the genetic variance explained by individual SNPs was highly skewed towards zero with a few SNPs obtaining large effects. Two-way epistasis was found between 14 pairs of candidate genes. Relatively low to medium empirical correlations of SNP-FT associations were observed across the three platforms underlining the need for multi-level experimentation for dissecting complex associations between genotypes and FT in rye. Conclusions Candidate gene based-association studies are a powerful tool for investigating the genetic basis of FT in rye. Results of this study support the findings of bi-parental linkage mapping and expression studies that the Cbf gene family plays an essential role in FT.

  15. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi

    2015-10-01

    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  16. Genetics of human longevity with emphasis on the relevance of HSP70 as candidate genes

    DEFF Research Database (Denmark)

    Singh, Ripudaman; Kølvrå, Steen; Rattan, Suresh I S

    2007-01-01

    mechanisms. One such pathway includes the battery of stress response genes, especially the heat shock protein HSP70 genes. Three such genes, HSPA1A, HSPA1B and HSPA1L, are present within the MHC-III region on the short arm of chromosome 6. We and others have found alleles, genotypes and haplotypes which have...... of an appropriate study design and methodology. Since aging is characterized by a progressive accumulation of molecular damage and an attenuation of the cellular defense mechanisms, the focus of studies on human longevity association with genes has now shifted to the pathways of cellular maintenance and repair...... to heat shock. Stress response genes, particularly HSP70, are now the major candidates in the gene-longevity association studies....

  17. The Drosophila gene brainiac encodes a glycosyltransferase putatively involved in glycosphingolipid synthesis

    DEFF Research Database (Denmark)

    Schwientek, Tilo; Keck, Birgit; Levery, Steven B;

    2002-01-01

    The Drosophila genes fringe and brainiac exhibit sequence similarities to glycosyltransferases. Drosophila and mammalian fringe homologs encode UDP-N-acetylglucosamine:fucose-O-Ser beta1,3-N-acetylglucosaminyltransferases that modulate the function of Notch family receptors. The biological function...

  18. Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model

    Institute of Scientific and Technical Information of China (English)

    LU Jia-hai; CHEN Wei-qing; LING Wen-hua; YU Xin-bing; ZHONG Nan-shan; ZHANG Ding-mei; WANG Guo-ling; GUO Zhong-min; ZHANG Chuan-hai; TAN Bing-yan; OUYANG Li-ping; LIN Li; LIU Yi-min

    2005-01-01

    Background The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CLpro, following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain.Methods The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein.Results The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7

  19. Evaluation of candidate reference genes for gene expression normalization in Brassica juncea using real time quantitative RT-PCR.

    Directory of Open Access Journals (Sweden)

    Ruby Chandna

    Full Text Available The real time quantitative reverse transcription PCR (qRT-PCR is becoming increasingly important to gain insight into function of genes. Given the increased sensitivity, ease and reproducibility of qRT-PCR, the requirement of suitable reference genes for normalization has become important and stringent. It is now known that the expression of internal control genes in living organism vary considerably during developmental stages and under different experimental conditions. For economically important Brassica crops, only a couple of reference genes are reported till date. In this study, expression stability of 12 candidate reference genes including ACT2, ELFA, GAPDH, TUA, UBQ9 (traditional housekeeping genes, ACP, CAC, SNF, TIPS-41, TMD, TSB and ZNF (new candidate reference genes, in a diverse set of 49 tissue samples representing different developmental stages, stress and hormone treated conditions and cultivars of Brassica juncea has been validated. For the normalization of vegetative stages the ELFA, ACT2, CAC and TIPS-41 combination would be appropriate whereas TIPS-41 along with CAC would be suitable for normalization of reproductive stages. A combination of GAPDH, TUA, TIPS-41 and CAC were identified as the most suitable reference genes for total developmental stages. In various stress and hormone treated samples, UBQ9 and TIPS-41 had the most stable expression. Across five cultivars of B. juncea, the expression of CAC and TIPS-41 did not vary significantly and were identified as the most stably expressed reference genes. This study provides comprehensive information that the new reference genes selected herein performed better than the traditional housekeeping genes. The selection of most suitable reference genes depends on the experimental conditions, and is tissue and cultivar-specific. Further, to attain accuracy in the results more than one reference genes are necessary for normalization.

  20. Validation of putative reference genes for gene expression studies in human hepatocellular carcinoma using real-time quantitative RT-PCR

    International Nuclear Information System (INIS)

    Reference genes, which are often referred to as housekeeping genes are frequently used to normalize mRNA levels between different samples in quantitative reverse transcription polymerase chain reaction (qRT-PCR). The selection of reference genes is critical for gene expression studies because the expression of these genes may vary among tissues or cells and may change under certain circumstances. Here, a systematic evaluation of six putative reference genes for gene expression studies in human hepatocellular carcinoma (HCC) is presented. Six genes, beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hydroxymethyl-bilane synthase (HMBS), hypoxanthine phosphoribosyl-transferase 1 (HPRT1), succinate dehydrogenase complex, subunit A (SDHA) and ubiquitin C (UBC), with distinct functional characteristics and expression patterns were evaluated by qRT-PCR. Inhibitory substances in RNA samples were quantitatively assessed and controlled using an external RNA control. The stability of selected reference genes was analyzed using both geNorm and NormFinder software. HMBS and GAPDH were identified as the optimal reference genes for normalizing gene expression data between paired tumoral and adjacent non-tumoral tissues derived from patients with HCC. HMBS, GAPDH and UBC were identified to be suitable for the normalization of gene expression data among tumor tissues; whereas the combination of HMBS, B2M, SDHA and GAPDH was suitable for normalizing gene expression data among five liver cancer cell lines, namely Hep3B, HepG2, HuH7, SK-HEP-1 and SNU-182. The determined gene stability was increased after exclusion of RNA samples containing relatively higher inhibitory substances. Of six genes studied, HMBS was found to be the single best reference gene for gene expression studies in HCC. The appropriate choice of combination of more than one reference gene to improve qRT-PCR accuracy depends on the kind of liver tissues or cells under investigation

  1. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

    Science.gov (United States)

    Hart, Robert J.; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S.; Ben Mamoun, Choukri; Aly, Ahmed S. I.

    2016-01-01

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes. PMID:27644319

  2. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.

    Science.gov (United States)

    Hart, Robert J; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S; Ben Mamoun, Choukri; Aly, Ahmed S I

    2016-01-01

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes. PMID:27644319

  3. Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation.

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Robb

    Full Text Available The chicken coloboma mutation exhibits features similar to human congenital developmental malformations such as ocular coloboma, cleft-palate, dwarfism, and polydactyly. The coloboma-associated region and encoded genes were investigated using advanced genomic, genetic, and gene expression technologies. Initially, the mutation was linked to a 990 kb region encoding 11 genes; the application of the genetic and genomic tools led to a reduction of the linked region to 176 kb and the elimination of 7 genes. Furthermore, bioinformatics analyses of capture array-next generation sequence data identified genetic elements including SNPs, insertions, deletions, gaps, chromosomal rearrangements, and miRNA binding sites within the introgressed causative region relative to the reference genome sequence. Coloboma-specific variants within exons, UTRs, and splice sites were studied for their contribution to the mutant phenotype. Our compiled results suggest three genes for future studies. The three candidate genes, SLC30A5 (a zinc transporter, CENPH (a centromere protein, and CDK7 (a cyclin-dependent kinase, are differentially expressed (compared to normal embryos at stages and in tissues affected by the coloboma mutation. Of these genes, two (SLC30A5 and CENPH are considered high-priority candidate based upon studies in other vertebrate model systems.

  4. Evolutionary conservation of candidate osmoregulation genes in plant phloem sap-feeding insects.

    Science.gov (United States)

    Jing, X; White, T A; Luan, J; Jiao, C; Fei, Z; Douglas, A E

    2016-06-01

    The high osmotic pressure generated by sugars in plant phloem sap is reduced in phloem-feeding aphids by sugar transformations and facilitated water flux in the gut. The genes mediating these osmoregulatory functions have been identified and validated empirically in the pea aphid Acyrthosiphon pisum: sucrase 1 (SUC1), a sucrase in glycoside hydrolase family 13 (GH13), and aquaporin 1 (AQP1), a member of the Drosophila integral protein (DRIP) family of aquaporins. Here, we describe molecular analysis of GH13 and AQP genes in phloem-feeding representatives of the four phloem-feeding groups: aphids (Myzus persicae), coccids (Planococcus citri), psyllids (Diaphorina citri, Bactericera cockerelli) and whiteflies (Bemisia tabaci MEAM1 and MED). A single candidate GH13-SUC gene and DRIP-AQP gene were identified in the genome/transcriptome of most insects tested by the criteria of sequence motif and gene expression in the gut. Exceptionally, the psyllid Ba. cockerelli transcriptome included a gut-expressed Pyrocoelia rufa integral protein (PRIP)-AQP, but has no DRIP-AQP transcripts, suggesting that PRIP-AQP is recruited for osmoregulatory function in this insect. This study indicates that phylogenetically related SUC and AQP genes may generally mediate osmoregulatory functions in these diverse phloem-feeding insects, and provides candidate genes for empirical validation and development as targets for osmotic disruption of pest species. PMID:26896054

  5. Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Karina Banasik

    Full Text Available OBJECTIVE: Candidate genes for non-alcoholic fatty liver disease (NAFLD identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. RESEARCH DESIGN AND METHODS: By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D, central obesity, and WHO-defined metabolic syndrome (MetS. RESULTS: 273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05 to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations. CONCLUSIONS: Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.

  6. KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers.

    Directory of Open Access Journals (Sweden)

    Deborah G Murdock

    Full Text Available Alzheimer disease (AD is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD. Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and "rokimi", encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either "rokimi", or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than "rokimi" which had no detectable expression in brain.

  7. Utilization of Gene Mapping and Candidate Gene Mutation Screening for Diagnosing Clinically Equivocal Conditions:A Norrie Disease Case Study

    Institute of Scientific and Technical Information of China (English)

    Vasiliki Chini; Danai Stambouli; Florina Mihaela Nedelea; George Alexandru Filipescu; Diana Mina; Marios Kambouris; Hatem El-Shanti

    2014-01-01

    Prenatal diagnosis was requested for an undiagnosed eye disease showing X-linked inheritance in a family. No medical records existed for the affected family members..Mapping of the X chromosome and candidate gene mutation screening i-dentified a c.C267A[p.F89L] mutation in NPD previously de-scribed as possibly causing Norrie disease..The detection of the c.C267A[p.F89L] variant in another unrelated family con-firms the pathogenic nature of the mutation for the Norrie dis-ease phenotype. Gene mapping, haplotype analysis, and can-didate gene screening have been previously utilized in research applications but were applied here in a diagnostic setting due to the scarcity of available clinical information..The clinical diagnosis and mutation identification were critical for provid-ing proper genetic counseling and prenatal diagnosis for this family.

  8. IDENTIFICATION AND HORMONE INDUCTION OF PUTATIVE CHITIN SYNTHASE GENES AND SPLICE VARIANTS IN Leptinotarsa decemlineata (SAY).

    Science.gov (United States)

    Shi, Ji-Feng; Mu, Li-Li; Guo, Wen-Chao; Li, Guo-Qing

    2016-08-01

    Chitin synthase (ChS) plays a critical role in chitin synthesis and excretion. In this study, two ChS genes (LdChSA and LdChSB) were identified in Leptinotarsa decemlineata. LdChSA contains two splicing variants, LdChSAa and LdChSAb. Within the first, second, and third larval instars, the mRNA levels of LdChSAa, LdChSAb, and LdChSB coincide with the peaks of circulating 20-hydroxyecdysone (20E) and juvenile hormone (JH). In vitro culture of midguts and an in vivo bioassay revealed that 20E and an ecdysteroid agonist halofenozide stimulated the expression of the three LdChSs. Conversely, a reduction of 20E by RNA interference (RNAi) of an ecdysteroidogenesis gene LdSHD repressed the expression of these LdChSs, and ingestion of halofenozide by LdSHD RNAi larvae rescued the repression. Moreover, disruption of 20E signaling by RNAi of LdEcR, LdE75, LdHR3, and LdFTZ-F1 reduced the expression levels of these genes. Similarly, in vitro culture and an in vivo bioassay showed that exogenous JH and a JH analog methoprene activated the expression of the three LdChSs, whereas a decrease in JH by RNAi of a JH biosynthesis gene LdJHAMT downregulated these LdChSs. It seems that JH upregulates LdChSs at the early stage of each instar, whereas a 20E pulse triggers the transcription of LdChSs during molting in L. decemlineata. PMID:27030662

  9. Identification of putative cancer genes through data integration and comparative genomics between plants and humans

    OpenAIRE

    Quimbaya, Mauricio; Vandepoele, Klaas; Raspé, Eric; Matthijs, Michiel; Dhondt, Stijn; Beemster, Gerrit T.S.; Berx, Geert; De Veylder, Lieven

    2012-01-01

    Abstract: Coordination of cell division with growth and development is essential for the survival of organisms. Mistakes made during replication of genetic material can result in cell death, growth defects, or cancer. Because of the essential role of the molecular machinery that controls DNA replication and mitosis during development, its high degree of conservation among organisms is not surprising. Mammalian cell cycle genes have orthologues in plants, and vice versa. However, besides the m...

  10. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Coral-Vázquez, Ramón M.; Hernández-Stengele, Gabriel; Sánchez, Raúl; Salazar, Emmanuel; Sanchez-Muñoz, Fausto; Encarnación-Guevara, Sergio; Ramírez-Salcedo, Jorge

    2013-01-01

    The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. PMID:24288657

  11. Identifying Candidate Genes for Type 2 Diabetes Mellitus and Obesity through Gene Expression Profiling in Multiple Tissues or Cells

    Science.gov (United States)

    Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

    2013-01-01

    Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity. PMID:24455749

  12. Identifying Candidate Genes for Type 2 Diabetes Mellitus and Obesity through Gene Expression Profiling in Multiple Tissues or Cells

    Directory of Open Access Journals (Sweden)

    Junhui Chen

    2013-01-01

    Full Text Available Type 2 Diabetes Mellitus (T2DM and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

  13. Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells.

    Science.gov (United States)

    Chen, Junhui; Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

    2013-01-01

    Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

  14. Selection and validation of potato candidate genes for maturity corrected resistance to Phytophthora infestans based on differential expression combined with SNP association and linkage mapping

    Directory of Open Access Journals (Sweden)

    Meki Shehabu Muktar

    2015-09-01

    Full Text Available Late blight of potato (Solanum tuberosum L. caused by the oomycete Phytophthora infestans (Mont. de Bary, is one of the most important bottlenecks of potato production worldwide. Cultivars with high levels of durable, race unspecific, quantitative resistance are part of a solution to this problem. However, breeding for quantitative resistance is hampered by the correlation between resistance and late plant maturity, which is an undesirable agricultural attribute. The objectives of our research are (i the identification of genes that condition quantitative resistance to P. infestans not compromised by late plant maturity and (ii the discovery of diagnostic single nucleotide polymorphism (SNP markers to be used as molecular tools to increase efficiency and precision of resistance breeding. Twenty two novel candidate genes were selected based on comparative transcript profiling by SuperSAGE (serial analysis of gene expression in groups of plants with contrasting levels of maturity corrected resistance (MCR. Reproducibility of differential expression was tested by quantitative real time PCR and allele specific pyrosequencing in four new sets of genotype pools with contrasting late blight resistance levels, at three infection time points and in three independent infection experiments. Reproducibility of expression patterns ranged from 28% to 97%. Association mapping in a panel of 184 tetraploid cultivars identified SNPs in five candidate genes that were associated with MCR. These SNPs can be used in marker-assisted resistance breeding. Linkage mapping in two half-sib families (n = 111 identified SNPs in three candidate genes that were linked with MCR. The differentially expressed genes that showed association and/or linkage with MCR putatively function in phytosterol synthesis, fatty acid synthesis, asparagine synthesis, chlorophyll synthesis, cell wall modification and in the response to pathogen elicitors.

  15. Expressed sequence tags from larval gut of the European corn borer (Ostrinia nubilalis: Exploring candidate genes potentially involved in Bacillus thuringiensis toxicity and resistance

    Directory of Open Access Journals (Sweden)

    Crespo Andre LB

    2009-06-01

    Full Text Available Abstract Background Lepidoptera represents more than 160,000 insect species which include some of the most devastating pests of crops, forests, and stored products. However, the genomic information on lepidopteran insects is very limited. Only a few studies have focused on developing expressed sequence tag (EST libraries from the guts of lepidopteran larvae. Knowledge of the genes that are expressed in the insect gut are crucial for understanding basic physiology of food digestion, their interactions with Bacillus thuringiensis (Bt toxins, and for discovering new targets for novel toxins for use in pest management. This study analyzed the ESTs generated from the larval gut of the European corn borer (ECB, Ostrinia nubilalis, one of the most destructive pests of corn in North America and the western world. Our goals were to establish an ECB larval gut-specific EST database as a genomic resource for future research and to explore candidate genes potentially involved in insect-Bt interactions and Bt resistance in ECB. Results We constructed two cDNA libraries from the guts of the fifth-instar larvae of ECB and sequenced a total of 15,000 ESTs from these libraries. A total of 12,519 ESTs (83.4% appeared to be high quality with an average length of 656 bp. These ESTs represented 2,895 unique sequences, including 1,738 singletons and 1,157 contigs. Among the unique sequences, 62.7% encoded putative proteins that shared significant sequence similarities (E-value ≤ 10-3with the sequences available in GenBank. Our EST analysis revealed 52 candidate genes that potentially have roles in Bt toxicity and resistance. These genes encode 18 trypsin-like proteases, 18 chymotrypsin-like proteases, 13 aminopeptidases, 2 alkaline phosphatases and 1 cadherin-like protein. Comparisons of expression profiles of 41 selected candidate genes between Cry1Ab-susceptible and resistant strains of ECB by RT-PCR showed apparently decreased expressions in 2 trypsin-like and 2

  16. Computational identification of putative miRNAs and their target genes in pathogenic amoeba Naegleria fowleri.

    Science.gov (United States)

    Padmashree, Dyavegowda; Swamy, Narayanaswamy Ramachandra

    2015-01-01

    Naegleria fowleri is a parasitic unicellular free living eukaryotic amoeba. The parasite spreads through contaminated water and causes primary amoebic meningoencephalitis (PAM). Therefore, it is of interest to understand its molecular pathogenesis. Hence, we analyzed the parasite genome for miRNAs (microRNAs) that are non-coding, single stranded RNA molecules. We identified 245 miRNAs using computational methods in N. fowleri, of which five miRNAs are conserved. The predicted miRNA targets were analyzed by using miRanda (software) and further studied the functions by subsequently annotating using AmiGo (a gene ontology web tool).

  17. Genome-Wide Association Study Identifies Candidate Genes for Starch Content Regulation in Maize Kernels

    Science.gov (United States)

    Liu, Na; Xue, Yadong; Guo, Zhanyong; Li, Weihua; Tang, Jihua

    2016-01-01

    Kernel starch content is an important trait in maize (Zea mays L.) as it accounts for 65–75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60 to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM) as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001), among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437) is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  18. Genome-Wide Association Study Identifies Candidate Genes for Starch Content Regulation in Maize Kernels.

    Science.gov (United States)

    Liu, Na; Xue, Yadong; Guo, Zhanyong; Li, Weihua; Tang, Jihua

    2016-01-01

    Kernel starch content is an important trait in maize (Zea mays L.) as it accounts for 65-75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60 to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM) as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001), among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437) is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops. PMID:27512395

  19. Genome scans reveal candidate domestication and improvement genes in cultivated sunflower, as well as post-domestication introgression with wild relatives.

    Science.gov (United States)

    Baute, Gregory J; Kane, Nolan C; Grassa, Christopher J; Lai, Zhao; Rieseberg, Loren H

    2015-04-01

    The development of modern crops typically involves both selection and hybridization, but to date most studies have focused on the former. In the present study, we explore how both processes, and their interactions, have molded the genome of the cultivated sunflower (Helianthus annuus), a globally important oilseed. To identify genes targeted by selection during the domestication and improvement of sunflower, and to detect post-domestication hybridization with wild species, we analyzed transcriptome sequences of 80 genotypes, including wild, landrace, and modern lines of H. annuus, as well as two cross-compatible wild relatives, Helianthus argophyllus and Helianthus petiolaris. Outlier analyses identified 122 and 15 candidate genes associated with domestication and improvement, respectively. As in several previous studies, genes putatively involved in oil biosynthesis were the most extreme outliers. Additionally, several promising associations were observed with previously mapped quantitative trait loci (QTLs), such as branching. Admixture analyses revealed that all the modern cultivar genomes we examined contained one or more introgressions from wild populations, with every chromosome having evidence of introgression in at least one modern line. Cumulatively, introgressions cover c. 10% of the cultivated sunflower genome. Surprisingly, introgressions do not avoid candidate domestication genes, probably because of the reintroduction of branching.

  20. Genome scans reveal candidate domestication and improvement genes in cultivated sunflower, as well as post-domestication introgression with wild relatives.

    Science.gov (United States)

    Baute, Gregory J; Kane, Nolan C; Grassa, Christopher J; Lai, Zhao; Rieseberg, Loren H

    2015-04-01

    The development of modern crops typically involves both selection and hybridization, but to date most studies have focused on the former. In the present study, we explore how both processes, and their interactions, have molded the genome of the cultivated sunflower (Helianthus annuus), a globally important oilseed. To identify genes targeted by selection during the domestication and improvement of sunflower, and to detect post-domestication hybridization with wild species, we analyzed transcriptome sequences of 80 genotypes, including wild, landrace, and modern lines of H. annuus, as well as two cross-compatible wild relatives, Helianthus argophyllus and Helianthus petiolaris. Outlier analyses identified 122 and 15 candidate genes associated with domestication and improvement, respectively. As in several previous studies, genes putatively involved in oil biosynthesis were the most extreme outliers. Additionally, several promising associations were observed with previously mapped quantitative trait loci (QTLs), such as branching. Admixture analyses revealed that all the modern cultivar genomes we examined contained one or more introgressions from wild populations, with every chromosome having evidence of introgression in at least one modern line. Cumulatively, introgressions cover c. 10% of the cultivated sunflower genome. Surprisingly, introgressions do not avoid candidate domestication genes, probably because of the reintroduction of branching. PMID:25641359

  1. Transcriptome and Metabolite analysis reveal candidate genes of the cardiac glycoside biosynthetic pathway from Calotropis procera

    Science.gov (United States)

    Pandey, Akansha; Swarnkar, Vishakha; Pandey, Tushar; Srivastava, Piush; Kanojiya, Sanjeev; Mishra, Dipak Kumar; Tripathi, Vineeta

    2016-01-01

    Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG’s were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair. Around 66.6% of unigenes were annotated by using various public databases and 5324 unigenes showed significant match in the KEGG database involved in 133 different pathways of plant metabolism. Further KEGG analysis resulted in identification of 336 unigenes involved in cardenolide biosynthesis. Tissue specific expression analysis of 30 putative transcripts involved in terpenoid, steroid and cardenolide pathways showed a positive correlation between metabolite and transcript accumulation. Wound stress elevated CG levels as well the levels of the putative transcripts involved in its biosynthetic pathways. This result further validated the involvement of identified transcripts in CGs biosynthesis. The identified transcripts will lay a substantial foundation for further research on metabolic engineering and regulation of cardiac glycosides biosynthesis pathway genes. PMID:27703261

  2. Analysis of the expression of putative heat-stress related genes in relation to thermotolerance of cork oak.

    Science.gov (United States)

    Correia, Barbara; Rodriguez, José Luis; Valledor, Luis; Almeida, Tânia; Santos, Conceição; Cañal, Maria Jesús; Pinto, Glória

    2014-03-15

    Cork oak (Quercus suber L.) is a research priority in the Mediterranean area and because of cork oaks' distribution these stands are experiencing daily stress. Based on projections of intensifying climate change and considering the key role of exploring the recovery abilities, cork oak seedlings were subjected to a cumulative temperature increase from 25°C to 55°C and subsequent recovery. CO2 assimilation rate, chlorophyll fluorescence, anthocyanins, proline and lipid peroxidation were used to evaluate plant performance, while the relative abundance of seven genes encoding for proteins of cork oak with a putative role in thermal/stress regulation (POX1, POX2, HSP10.4, HSP17a.22, CHS, MTL and RBC) was analyzed by qPCR (quantitative Polymerase Chain Reaction). A temperature change to 35°C showed abundance alterations in the tested genes; at 45°C, the molecular changes were associated with an antioxidant response, possibly modulated by anthocyanins. At 55°C, HSP17a.22, MTL and proline accumulation were evident. After recovery, physiological balance was restored, whereas POX1, HSP10.4 and MTL abundances were suggested to be involved in increased thermotolerance. The data presented here are expected to pinpoint some pathways changes occurring during such stress and further recovery in this particular Mediterranean species.

  3. Isolation and Characterization of a Putative Class E Gene from Taihangia rupestris

    Institute of Scientific and Technical Information of China (English)

    Yong-Qiang Wang; Hui-Yu Tian; Xiao-Qiu Du; Shan-Hua Lü; Wen-Liang Lu; Kang Chong; Zheng Meng

    2007-01-01

    Studies in model plants showed that SEPALLATA (SEP) genes are required for the identification of floral organs and the determination of floral meristems in Arabldopsls. In this paper a SEP homolog, TrSEP3, was Isolated from a SEP3-clade of SEP (prevlous AGL2) subfamily. In sltu hybridization was used to reveal the potential functional specification, and the results showed that TrSEP3 expression was first observed in floral meristems and then confined to the floral primordia of the three inner whorls. In the matured flower, TrSEP3 was strongly expressed in the tips of pistils and weak in stamens and petals. The evolution force analysis shows that TrSEP3 might undergo a relaxed negative selection. These results suggested that TrSEP3 may not only function in determining the identity of floral meristems and the primordia of three inner whorls, but also function in matured reproductive organs.

  4. Identification of two new drought specific candidate genes in sugarcane (Saccharum spp.

    Directory of Open Access Journals (Sweden)

    Swapna Simon and G. Hemaprabha

    2010-07-01

    Full Text Available Effective identification and understanding of genes contribute to improve plant drought resistance. A study was conducted toidentify drought responsive candidate genes in sugarcane. Two genes viz., SOD (Superoxide dismutase and IGS (Indole 3-glycerol phosphate synthase were used as gene specific markers. Specific primers were designed based on the sequences inGenbank databases. Mapping population developed by crossing a drought tolerant parent (Co 740 and a drought susceptibleparent (Co 775 were phenotyped using physiological and sugar yield contributing parameters and were characterized into groupsof varying levels of resistance and susceptibility. Parental polymorphism for SOD and IGS specific primers was established usinggenomic DNA from field grown drought tolerant and susceptible parents, as the presence in Co 740 (resistant and absence in Co775 (susceptible respectively. Resistant and susceptible parents and six each resistant and susceptible progeny were subjected todrought imposition and RNA were isolated and RT - PCR analysis performed using these gene specific primers. A specific bandof 618 bp was identified in drought tolerant parent and progeny, absent in drought susceptible parent and progeny genotypedusing SOD gene. A specific band of 340 bp was identified in drought tolerant parent and progeny while it was absent in droughtsusceptible parent and progeny genotyped using IGS gene. These two fragments of interests were cloned in PTz57R/T vector andsequenced. SOD618 sequence was BLAST searched that showed 98 % homology with the drought inducible protein in Saccharumhybrid and IGS340 showed 80 % homology with the hypothetical protein expressed in rice genome. These new genes hold promiseimproving drought resistance of sugarcane through their use as candidate genes in marker assisted selection and in genetictransformation.

  5. Genetic relationships of some Citrus genotypes based on the candidate iron chlorosis genes

    OpenAIRE

    KAÇAR, Yıldız AKA; Özhan ŞİMŞEK; DÖNMEZ, Dicle; BONCUK, Melda; YEŞİLOĞLU, Turgut; Ollitrault, Patrick

    2014-01-01

    Iron is one of the most important elements in plant mineral nutrition. Fe deficiency is a critical abiotic stress factor for Mediterranean citriculture; the development of marker-assisted selection for this trait would greatly enhance rootstock breeding. In this study, DNA sequencing and single-stranded conformation polymorphism (SSCP) analyses were performed to determine the allelic diversity of genes associated with tolerance to iron chlorosis in citrus. Two candidate iron chlorosis toleran...

  6. Tales of one gene discovery of a novel candidate receptor in mammalian taste

    OpenAIRE

    Huang, Angela Lilly

    2007-01-01

    There are five basic taste modalities in mammals: bitter, sweet, sour, salty, and Umami (taste of MSG and L-amino acids). Receptors for bitter, sweet, and Umami were previously discovered. Identities of receptors for salty and sour taste modalities remained elusive. In this dissertation, I will present: 1) development of a novel bioinformatics screen to discover candidate receptors; 2) discovery of a novel gene, PKD2L1, in taste receptor cells; 3) evidence demonstrating PKD2L1-expressing tast...

  7. A comprehensive genetic analysis of candidate genes regulating response to Trypanosoma congolense infection in mice.

    Directory of Open Access Journals (Sweden)

    Ian Goodhead

    Full Text Available BACKGROUND: African trypanosomes are protozoan parasites that cause "sleeping sickness" in humans and a similar disease in livestock. Trypanosomes also infect laboratory mice and three major quantitative trait loci (QTL that regulate survival time after infection with T. congolense have been identified in two independent crosses between susceptible A/J and BALB/c mice, and the resistant C57BL/6. These were designated Tir1, Tir2 and Tir3 for Trypanosoma infection response, and range in size from 0.9-12 cM. PRINCIPAL FINDINGS: Mapping loci regulating survival time after T. congolense infection in an additional cross revealed that susceptible C3H/HeJ mice have alleles that reduce survival time after infection at Tir1 and Tir3 QTL, but not at Tir2. Next-generation resequencing of a 6.2 Mbp region of mouse chromosome 17, which includes Tir1, identified 1,632 common single nucleotide polymorphisms (SNP including a probably damaging non-synonymous SNP in Pram1 (PML-RAR alpha-regulated adaptor molecule 1, which was the most plausible candidate QTL gene in Tir1. Genome-wide comparative genomic hybridisation identified 12 loci with copy number variants (CNV that correlate with differential gene expression, including Cd244 (natural killer cell receptor 2B4, which lies close to the peak of Tir3c and has gene expression that correlates with CNV and phenotype, making it a strong candidate QTL gene at this locus. CONCLUSIONS: By systematically combining next-generation DNA capture and sequencing, array-based comparative genomic hybridisation (aCGH, gene expression data and SNP annotation we have developed a strategy that can generate a short list of polymorphisms in candidate QTL genes that can be functionally tested.

  8. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  9. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shi, CY; Yang, H; Wei, CL; Yu, O; Zhang, ZZ; Sun, J; Wan, XC

    2011-01-01

    Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Using high-throughput Illumina RNA-seq, the transcriptome from poly (A){sup +} RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010). Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG) found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were analyzed by RT-PCR and quantitative real

  10. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Directory of Open Access Journals (Sweden)

    Chen Qi

    2011-02-01

    Full Text Available Abstract Background Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Results Using high-throughput Illumina RNA-seq, the transcriptome from poly (A+ RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs. Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010. Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were

  11. Flavonoid Biosynthesis Genes Putatively Identified in the Aromatic Plant Polygonum minus via Expressed Sequences Tag (EST Analysis

    Directory of Open Access Journals (Sweden)

    Zamri Zainal

    2012-02-01

    Full Text Available P. minus is an aromatic plant, the leaf of which is widely used as a food additive and in the perfume industry. The leaf also accumulates secondary metabolites that act as active ingredients such as flavonoid. Due to limited genomic and transcriptomic data, the biosynthetic pathway of flavonoids is currently unclear. Identification of candidate genes involved in the flavonoid biosynthetic pathway will significantly contribute to understanding the biosynthesis of active compounds. We have constructed a standard cDNA library from P. minus leaves, and two normalized full-length enriched cDNA libraries were constructed from stem and root organs in order to create a gene resource for the biosynthesis of secondary metabolites, especially flavonoid biosynthesis. Thus, large‑scale sequencing of P. minus cDNA libraries identified 4196 expressed sequences tags (ESTs which were deposited in dbEST in the National Center of Biotechnology Information (NCBI. From the three constructed cDNA libraries, 11 ESTs encoding seven genes were mapped to the flavonoid biosynthetic pathway. Finally, three flavonoid biosynthetic pathway-related ESTs chalcone synthase, CHS (JG745304, flavonol synthase, FLS (JG705819 and leucoanthocyanidin dioxygenase, LDOX (JG745247 were selected for further examination by quantitative RT-PCR (qRT-PCR in different P. minus organs. Expression was detected in leaf, stem and root. Gene expression studies have been initiated in order to better understand the underlying physiological processes.

  12. De novo transcriptome of safflower and the identification of putative genes for oleosin and the biosynthesis of flavonoids.

    Directory of Open Access Journals (Sweden)

    Haiyan Li

    Full Text Available Safflower (Carthamus tinctorius L. is one of the most extensively used oil crops in the world. However, little is known about how its compounds are synthesized at the genetic level. In this study, Solexa-based deep sequencing on seed, leaf and petal of safflower produced a de novo transcriptome consisting of 153,769 unigenes. We annotated 82,916 of the unigenes with gene annotation and assigned functional terms and specific pathways to a subset of them. Metabolic pathway analysis revealed that 23 unigenes were predicted to be responsible for the biosynthesis of flavonoids and 8 were characterized as seed-specific oleosins. In addition, a large number of differentially expressed unigenes, for example, those annotated as participating in anthocyanin and chalcone synthesis, were predicted to be involved in flavonoid biosynthesis pathways. In conclusion, the de novo transcriptome investigation of the unique transcripts provided candidate gene resources for studying oleosin-coding genes and for investigating genes related to flavonoid biosynthesis and metabolism in safflower.

  13. Candidate genes expressed in human islets and their role in the pathogenesis of type 1 diabetes

    DEFF Research Database (Denmark)

    Storling, Joachim; Brorsson, Caroline Anna

    2013-01-01

    In type 1 diabetes (T1D), the insulin-producing β cells are destroyed by an immune-mediated process leading to complete insulin deficiency. There is a strong genetic component in T1D. Genes located in the human leukocyte antigen (HLA) region are the most important genetic determinants of disease......, but more than 40 additional loci are known to significantly affect T1D risk. Since most of the currently known genetic candidates have annotated immune cell functions, it is generally considered that most of the genetic susceptibility in T1D is caused by variation in genes affecting immune cell function...

  14. Screening for candidate genes related to breast cancer with cDNA microarray analysis

    Institute of Scientific and Technical Information of China (English)

    Yu-Juan Xiang; Zhi-Gang Yu; Ming-Ming Guo; Qin-Ye Fu; Zhong-Bing Ma; De-Zong Gao; Qiang Zhang; Yu-Yang Li; Liang Li; Lu Liu; Chun-Miao Ye

    2015-01-01

    Objective: The aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease. Methods: We compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quanti-tatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis. Results: A total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis. Conclusion: Our present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer. Copyright © 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  15. Sequencing of Candidate Genes Selected by Beta Cell Experts in Monogenic Diabetes of Unknown Aetiology

    Directory of Open Access Journals (Sweden)

    Emma L Edghill

    2010-01-01

    Full Text Available Context Approximately 39% of cases with permanent neonatal diabetes (PNDM and about 11% with maturity onset diabetes of the young (MODY have an unknown genetic aetiology. Many of the known genes causing MODY and PNDM were identified as being critical for beta cell function before their identification as a cause of monogenic diabetes. Objective We used nominations from the EU beta cell consortium EURODIA project partners to guide gene candidacy. Subjects Seventeen cases with permanent neonatal diabetes and 8 cases with maturity onset diabetes of the young. Main outcome measures The beta cell experts within the EURODIA consortium were asked to nominate 3 “gold”, 3 “silver” and 4 “bronze” genes based on biological or genetic grounds. We sequenced twelve candidate genes from the list based on evidence for candidacy. Results Sequencing ISL1, LMX1A, MAFA, NGN3, NKX2.2, NKX6.1, PAX4, PAX6, SOX2, SREBF1, SYT9 and UCP2 did not identify any pathogenic mutations. Conclusion Further work is needed to identify novel causes of permanent neonatal diabetes and maturity onset diabetes of the young utilising genetic approaches as well as further candidate genes.

  16. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

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    Ma Menggen

    2010-06-01

    Full Text Available Abstract Background Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. Results A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Conclusion Enriched background of transcription abundance

  17. PXA1, a putative S. cerevisiae homolog of the human adrenoleukyodystrophy gene

    Energy Technology Data Exchange (ETDEWEB)

    Shani, N.; Watkins, P.A.; Valle, D. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)

    1994-09-01

    The adrenoleukodystrophy protein (ALDP) and the 70 kD peroxisomal membrane protein (PMP70) are ATP-binding cassette transporters in the peroxisome membrane. The former is defective in X-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder with defective peroxisome oxidation of very long chain fatty acids; the latter is implicated in Zellweger syndrome, a defect in peroxisome biogenesis. The functions and interactions of ALDP and PMP70 in the peroxisomal membrane are not known. To develop a system in which these questions could be addressed, we sought to clone their yeast homologs. Using RT/PCR with degenerate primers and oleic acid (C18:1) induced yeast RNA as template, we amplified a cDNA segment corresponding to a conserved region of ALDP and PMP70. By sequencing amplified products, we found one with homology to both proteins and used it to clone the corresponding full length yeast gene (PXA1). PXA1 encodes a 758 amino acid protein with 28% and 21% overall identity to ALDP and PMP70, respectively which increases to 47% and 39% in a C terminal region of 178 amino acids. The PXA1 protein precipitates with peroxisomes as shown by immunoblot analysis of cell fractionation gradients. Disruption of PXA1 by homologous recombination results in impaired growth on oleic acid and reduced ability to oxidize oleate. The growth phenotype can be corrected by expression of the wild type PXA1 in the mutant strain. Peroxisomes in the PXA1 mutant yeast strain are intact as judged by catalase distribution and electron microscopy. Given the amino acid similarity, fatty acid oxidation defect and lack of an effect on peroxisomal integrity, we hypothesize that PXA1 may be the yeast ortholog of ALDP. Complementation studies to examine this hypothesis are in progress.

  18. The genetic basis of quality of life in healthy Swedish women: a candidate gene approach.

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    Dounya Schoormans

    Full Text Available Quality of life (QoL is an increasingly important parameter in clinical practice as it predicts mortality and poor health outcomes. It is hypothesized that one may have a genetic predisposition for QoL. We therefore related 139 candidate genes, selected through a literature search, to QoL in healthy females.In 5,142 healthy females, background characteristics (i.e. demographic, clinical, lifestyle, and psychological factors were assessed. QoL was measured by the EORTC QLQ-C30, which consists of 15 domains. For all women genotype information was available. For each candidate gene, single nucleotide polymorphisms (SNPs were identified based on their functional (n = 2,663 and physical annotation (n = 10,649. SNPs were related to each QoL-domain, while controlling for background characteristics and population stratification. Finally, gene-based analyses were performed relating the combined effect of 10,649 SNPs (selected based on physical annotation for each gene, to QoL using the statistical software package VEGAS.Overall, we found no relation between genetic variations (SNPs and genes and 14 out of 15 QoL-domains. The strongest association was found between cognitive functioning and the top SNP rs1468951 (p = 1.21E-05 in the GSTZ1 gene. Furthermore, results of the gene-based test showed that the combined effect of 11 SNPs within the GSTZ1 gene is significantly associated with cognitive functioning (p = 2.60E-05.If validated, the involvement of GSTZ1 in cognitive functioning underscores its heritability which is likely the result of differences in the dopamine pathway, as GSTZ1 contributes to the equilibrium between dopamine and its neurotoxic metabolites via the glutathione redox cycle.

  19. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    OpenAIRE

    Rajani Rai; Jong Joo Kim; Sanjeev Misra; Ashok Kumar; Balraj Mittal

    2015-01-01

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactio...

  20. Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma.

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    Jason D Christie

    Full Text Available Acute Lung Injury (ALI is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1, we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs at p<0.01 to a replication phase (Phase 2 comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3 using expression quantitative trait loci (eQTL analyses in stimulated B-lymphoblastoid cell lines (B-LCL in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021. PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.

  1. Natural Genetic Variation and Candidate Genes for Morphological Traits in Drosophila melanogaster.

    Science.gov (United States)

    Carreira, Valeria Paula; Mensch, Julián; Hasson, Esteban; Fanara, Juan José

    2016-01-01

    Body size is a complex character associated to several fitness related traits that vary within and between species as a consequence of environmental and genetic factors. Latitudinal and altitudinal clines for different morphological traits have been described in several species of Drosophila and previous work identified genomic regions associated with such variation in D. melanogaster. However, the genetic factors that orchestrate morphological variation have been barely studied. Here, our main objective was to investigate genetic variation for different morphological traits associated to the second chromosome in natural populations of D. melanogaster along latitudinal and altitudinal gradients in Argentina. Our results revealed weak clinal signals and a strong population effect on morphological variation. Moreover, most pairwise comparisons between populations were significant. Our study also showed important within-population genetic variation, which must be associated to the second chromosome, as the lines are otherwise genetically identical. Next, we examined the contribution of different candidate genes to natural variation for these traits. We performed quantitative complementation tests using a battery of lines bearing mutated alleles at candidate genes located in the second chromosome and six second chromosome substitution lines derived from natural populations which exhibited divergent phenotypes. Results of complementation tests revealed that natural variation at all candidate genes studied, invected, Fasciclin 3, toucan, Reticulon-like1, jing and CG14478, affects the studied characters, suggesting that they are Quantitative Trait Genes for morphological traits. Finally, the phenotypic patterns observed suggest that different alleles of each gene might contribute to natural variation for morphological traits. However, non-additive effects cannot be ruled out, as wild-derived strains differ at myriads of second chromosome loci that may interact

  2. Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.

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    Alexandre R Vieira

    2005-12-01

    Full Text Available Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father. The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Etude du Polymorphisme Humain (CEPH diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate. Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.

  3. Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father. The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Etude du Polymorphisme Humain (CEPH diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate. Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.

  4. Characterization of candidate genes in inflammatory bowel disease–associated risk loci

    Science.gov (United States)

    Peloquin, Joanna M.; Sartor, R. Balfour; Newberry, Rodney D.; McGovern, Dermot P.; Yajnik, Vijay; Lira, Sergio A.

    2016-01-01

    GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn’s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis. PMID:27668286

  5. Polymorphisms of the endothelial nitric oxide synthase (NOS3 gene in preeclampsia: a candidate-gene association study

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    Messinis Ioannis E

    2011-11-01

    Full Text Available Abstract Background The endothelial nitric oxide synthase gene (NOS3 has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin. Methods We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia. Results The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association. Conclusions Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.

  6. Phylogenomic study of lipid genes involved in microalgal biofuel production-candidate gene mining and metabolic pathway analyses.

    Science.gov (United States)

    Misra, Namrata; Panda, Prasanna Kumar; Parida, Bikram Kumar; Mishra, Barada Kanta

    2012-01-01

    Optimizing microalgal biofuel production using metabolic engineering tools requires an in-depth understanding of the structure-function relationship of genes involved in lipid biosynthetic pathway. In the present study, genome-wide identification and characterization of 398 putative genes involved in lipid biosynthesis in Arabidopsis thaliana Chlamydomonas reinhardtii, Volvox carteri, Ostreococcus lucimarinus, Ostreococcus tauri and Cyanidioschyzon merolae was undertaken on the basis of their conserved motif/domain organization and phylogenetic profile. The results indicated that the core lipid metabolic pathways in all the species are carried out by a comparable number of orthologous proteins. Although the fundamental gene organizations were observed to be invariantly conserved between microalgae and Arabidopsis genome, with increased order of genome complexity there seems to be an association with more number of genes involved in triacylglycerol (TAG) biosynthesis and catabolism. Further, phylogenomic analysis of the genes provided insights into the molecular evolution of lipid biosynthetic pathway in microalgae and confirm the close evolutionary proximity between the Streptophyte and Chlorophyte lineages. Together, these studies will improve our understanding of the global lipid metabolic pathway and contribute to the engineering of regulatory networks of algal strains for higher accumulation of oil. PMID:23032611

  7. A putative gene sbe3-rs for resistant starch mutated from SBE3 for starch branching enzyme in rice (Oryza sativa L..

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    Ruifang Yang

    Full Text Available Foods high in resistant starch (RS are beneficial to prevent various diseases including diabetes, colon cancers, diarrhea and chronic renal or hepatic diseases. Elevated RS in rice is important for public health since rice is a staple food for half of the world population. A japonica mutant 'Jiangtangdao 1' (RS = 11.67% was crossed with an indica cultivar 'Miyang 23' (RS = 0.41%. The mutant sbe3-rs that explained 60.4% of RS variation was mapped between RM6611 and RM13366 on chromosome 2 (LOD = 36 using 178 F(2 plants genotyped with 106 genome-wide polymorphic SSR markers. Using 656 plants from four F(3:4 families, sbe3-rs was fine mapped to a 573.3 Kb region between InDel 2 and InDel 6 using one STS, five SSRs and seven InDel markers. SBE3 which codes for starch branching enzyme was identified as a candidate gene within the putative region. Nine pairs of primers covering 22 exons were designed to sequence genomic DNA of the wild type for SBE3 and the mutant for sbe3-rs comparatively. Sequence analysis identified a missense mutation site where Leu-599 of the wild was changed to Pro-599 of the mutant in the SBE3 coding region. Because the point mutation resulted in the loss of a restriction enzyme site, sbe3-rs was not digested by a CAPS marker for SpeI site while SBE3 was. Co-segregation of the digestion pattern with RS content among 178 F(2 plants further supported sbe3-rs responsible for RS in rice. As a result, the CAPS marker could be used in marker-assisted breeding to develop rice cultivars with elevated RS which is otherwise difficult to accurately assess in crops. Transgenic technology should be employed for a definitive conclusion of the sbe3-rs.

  8. Lactobacillus plantarum gene clusters encoding putative cell-surface protein complexes for carbohydrate utilization are conserved in specific gram-positive bacteria

    OpenAIRE

    Muscariello Lidia; Boekhorst Jos; Siezen Roland; Molenaar Douwe; Renckens Bernadet; Kleerebezem Michiel

    2006-01-01

    Abstract Background Genomes of gram-positive bacteria encode many putative cell-surface proteins, of which the majority has no known function. From the rapidly increasing number of available genome sequences it has become apparent that many cell-surface proteins are conserved, and frequently encoded in gene clusters or operons, suggesting common functions, and interactions of multiple components. Results A novel gene cluster encoding exclusively cell-surface proteins was identified, which is ...

  9. Exploring candidate genes for pericarp russet pigmentation of sand pear (Pyrus pyrifolia via RNA-Seq data in two genotypes contrasting for pericarp color.

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    Yue-zhi Wang

    Full Text Available Sand pear (Pyrus pyrifolia russet pericarp is an important trait affecting both the quality and stress tolerance of fruits. This trait is controlled by a relative complex genetic process, with some fundamental biological questions such as how many and which genes are involved in the process remaining elusive. In this study, we explored differentially expressed genes between the russet- and green-pericarp offspring from the sand pear (Pyrus pyrifolia cv. 'Qingxiang' × 'Cuiguan' F1 group by RNA-seq-based bulked segregant analysis (BSA. A total of 29,100 unigenes were identified and 206 of which showed significant differences in expression level (log2fold values>1 between the two types of pericarp pools. Gene Ontology (GO analyses detected 123 unigenes in GO terms related to 'cellular_component' and 'biological_process', suggesting developmental and growth differentiations between the two types. GO categories associated with various aspects of 'lipid metabolic processes', 'transport', 'response to stress', 'oxidation-reduction process' and more were enriched with genes with divergent expressions between the two libraries. Detailed examination of a selected set of these categories revealed repressed expressions of candidate genes for suberin, cutin and wax biosynthesis in the russet pericarps.Genes encoding putative cinnamoyl-CoA reductase (CCR, cinnamyl alcohol dehydrogenase (CAD and peroxidase (POD that are involved in the lignin biosynthesis were suggested to be candidates for pigmentation of sand pear russet pericarps. Nine differentially expressed genes were analyzed for their expressions using qRT-PCR and the results were consistent with those obtained from Illumina RNA-sequencing. This study provides a comprehensive molecular biology insight into the sand pear pericarp pigmentation and appearance quality formation.

  10. Multiple Origins of Mutations in the mdr1 Gene--A Putative Marker of Chloroquine Resistance in P. vivax.

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    Mette L Schousboe

    2015-11-01

    Full Text Available Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR. Single nucleotide polymorphisms (SNPs in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored.In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS loci flanking the Pvmdr1 gene.We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles.SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5, 13.3% (n = 28 of the samples were single mutant MYF, 63.0% of samples (n = 133 were double mutant MYL, and 21.3% (n = 45 were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He, was seen in the complete sample set (He = 0.99, while He estimates for individual loci ranged from 0.00-0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic

  11. Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare)WRKY transcription factor family reveals putatively retained functions betweenmonocots and dicots

    Energy Technology Data Exchange (ETDEWEB)

    Mangelsen, Elke; Kilian, Joachim; Berendzen, Kenneth W.; Kolukisaoglu, Uner; Harter, Klaus; Jansson, Christer; Wanke, Dierk

    2008-02-01

    WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare), three different WRKY proteins have been characterized so far, as regulators in sucrose signaling, in pathogen defense, and in response to cold and drought, respectively. However, their phylogenetic relationship remained unresolved. In this study, we used the available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY) genes. According to their structural features the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs. HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in mono- and dicot species.

  12. ALLELIC VARIANTS AND EXPRESSION CANDIDATE GENES FOR ABDOMINAL FATMASS IN CHICKENS

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    Larkina T. A.

    2015-06-01

    Full Text Available The expression of nine candidate genes for QTL abdominal fat weight and relative abdominal fat content was investigated by real-time polymerase chain reaction (PCR in the liver, adipose tissue, colon, muscle, pituitary gland and brain of broilers. The high mobility group AT hook1 (HMG1A gene was up-regulated in liver with aratio of means of 2,90 (P≤0,01 in the «fatty» group (relative abdominal fat content 3,5±0.18%, abdominal fat weight 35,4±6,09 g relative to the «lean» group (relative abdominal fat content 1,9±0,56%, abdominal fat weight 19,2±5,06 g. Expression of this gene was highly correlated with the relative abdominal fat content (0,70, P≤0,01 and abdominal fat weight (0,70, P≤0,01. The peroxisomeproliferator-activated receptor gamma (PPARG gene was also up-regulated in the liver with a ratio of means of 3,34(P≤0,01 in the «fatty» group relative to the «lean» group. Correlation of its expression was significant with both the relative abdominal fat content (0,55, P≤0,05 and the abdominal fat weight (0,57, P≤0,01. These data obtained and the data of references will allow the statement that the HMG1A, PPARG and FABP2 genes were candidate genes for abdominal fat deposition in chickens. Searching of rSNPs in regulatory regions of thesegenes could provide a tool for gene-assisted selection

  13. Genome-wide linkage analysis of global gene expression in loin muscle tissue identifies candidate genes in pigs.

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    Juan Pedro Steibel

    Full Text Available BACKGROUND: Nearly 6,000 QTL have been reported for 588 different traits in pigs, more than in any other livestock species. However, this effort has translated into only a few confirmed causative variants. A powerful strategy for revealing candidate genes involves expression QTL (eQTL mapping, where the mRNA abundance of a set of transcripts is used as the response variable for a QTL scan. METHODOLOGY/PRINCIPAL FINDINGS: We utilized a whole genome expression microarray and an F(2 pig resource population to conduct a global eQTL analysis in loin muscle tissue, and compared results to previously inferred phenotypic QTL (pQTL from the same experimental cross. We found 62 unique eQTL (FDR <10% and identified 3 gene networks enriched with genes subject to genetic control involved in lipid metabolism, DNA replication, and cell cycle regulation. We observed strong evidence of local regulation (40 out of 59 eQTL with known genomic position and compared these eQTL to pQTL to help identify potential candidate genes. Among the interesting associations, we found aldo-keto reductase 7A2 (AKR7A2 and thioredoxin domain containing 12 (TXNDC12 eQTL that are part of a network associated with lipid metabolism and in turn overlap with pQTL regions for marbling, % intramuscular fat (% fat and loin muscle area on Sus scrofa (SSC chromosome 6. Additionally, we report 13 genomic regions with overlapping eQTL and pQTL involving 14 local eQTL. CONCLUSIONS/SIGNIFICANCE: Results of this analysis provide novel candidate genes for important complex pig phenotypes.

  14. DGAT1, a new positional and functional candidate gene for intramuscular fat deposition in cattle.

    Science.gov (United States)

    Thaller, G; Kühn, C; Winter, A; Ewald, G; Bellmann, O; Wegner, J; Zühlke, H; Fries, R

    2003-10-01

    Intramuscular fat content, also assessed as marbling of meat, represents an important beef quality trait. Recent work has mapped a quantitative trait locus (QTL) with an effect on marbling to the centromeric region of bovine chromosome 14, with the gene encoding thyroglobulin (TG) being proposed as a positional and functional candidate gene for this QTL. Recently, the gene encoding diacylglycerol O-acyltransferase (DGAT1), which also has been mapped within the region of the marbling QTL, has been demonstrated to affect the fat content of milk. In the present study, the effects of a 5'-polymorphism of TG and of a lysine/alanine polymorphism of DGAT1 on the fat content of musculus (m.) semitendinosus and m. longissimus dorsi in 55 bovine animals (28 German Holstein and 27 Charolais) has been investigated. Significant effects were found for both candidate genes in both the breeds. These effects seem to be independent of one another because the alleles of the two polymorphisms showed no statistically significant disequilibrium. The DGAT1 effect is mainly on the m. semitendinosus. The TG polymorphism only affects m. longissimus dorsi. However, both intramuscular fat enhancing effects seem to be recessive. The possibility of two linked loci, acting recessively on intramuscular fat content, will require special strategies when selecting for higher marbling scores. PMID:14510671

  15. Identification of genes coding for putative wax ester synthase/diacylglycerol acyltransferase enzymes in terrestrial and marine environments.

    Science.gov (United States)

    Lanfranconi, Mariana P; Alvarez, Adrián F; Alvarez, Héctor M

    2015-12-01

    Synthesis of neutral lipids such as triacylglycerols (TAG) and wax esters (WE) is catalyzed in bacteria by wax ester synthase/diacylglycerol acyltransferase enzymes (WS/DGAT). We investigated the diversity of genes encoding this enzyme in contrasting natural environments from Patagonia (Argentina). The content of petroleum hydrocarbons in samples collected from oil-producing areas was measured. PCR-based analysis covered WS/DGAT occurrence in marine sediments and soil. No product was obtained in seawater samples. All clones retrieved from marine sediments affiliated with gammaproteobacterial sequences and within them, most phylotypes formed a unique cluster related to putative WS/DGAT belonging to marine OM60 clade. In contrast, soils samples contained phylotypes only related to actinomycetes. Among them, phylotypes affiliated with representatives largely or recently reported as oleaginous bacteria, as well as with others considered as possible lipid-accumulating bacteria based on the analysis of their annotated genomes. Our study shows for the first time that the environment could contain a higher variety of ws/dgat than that reported from bacterial isolates. The results of this study highlight the relevance of the environment in a natural process such as the synthesis and accumulation of neutral lipids. Particularly, both marine sediments and soil may serve as a useful source for novel WS/DGAT with biotechnological interest. PMID:26228353

  16. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene

    International Nuclear Information System (INIS)

    Additional mutations in the cystic fibrosis (CF) gene were identified in the regions corresponding to the two putative nucleotide (ATP)-binding folds (NBFs) of the predicted polypeptide. The patient cohort included 46 Canadian CF families with well-characterized DNA marker haplotypes spanning the disease locus and several other families from Israel. Eleven mutations were found in the first NBF, 2 were found in the second NBF, but none was found in the R-domain. Seven of the mutations were of the missense type affecting some of the highly conserved amino acid residues in the first NBF; 3 were nonsense mutations; 2 would probably affect mRNA splicing; 2 corresponded to small deletions, including another 3-base-pair deletion different from the major mutation (δF508), which could account for 70% of the CF chromosomes in the population. Nine of these mutations accounted for 12 of the 31 non-δF508 CF chromosomes in the Canadian families. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward

  17. Targeting 160 candidate genes for blood pressure regulation with a genome-wide genotyping array.

    Directory of Open Access Journals (Sweden)

    Siim Sõber

    Full Text Available The outcome of Genome-Wide Association Studies (GWAS has challenged the field of blood pressure (BP genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany to address (i SNP coverage in 160 BP candidate genes; (ii the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region+/-10 kb covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11 to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (>0.2 SNPs/kb revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P<0.05/2319, P<2.15 x 10(-5, the strength of some detected associations was close to this level: rs10889553 (LEPR and systolic BP (SBP (P = 4.5 x 10(-5 as well as rs10954174 (LEP and diastolic BP (DBP (P = 5.20 x 10(-5. In total, 12 markers in 7 genes (ADRA2A, LEP, LEPR, PTGER3, SLC2A1, SLC4A2, SLC8A1 revealed considerable association (P<10(-3 either with SBP, DBP, and/or hypertension (HYP. None of these were confirmed in replication samples (KORA S4, HYPEST, BRIGHT. However, supportive evidence for the association of rs10889553 (LEPR and rs11195419 (ADRA2A with BP was obtained in meta-analysis across samples stratified either by body mass index, smoking or alcohol consumption. Haplotype analysis highlighted LEPR and PTGER3. In conclusion, the lack of associations in BP candidate genes may be attributed to inadequate marker coverage on the genome-wide arrays, small phenotypic effects of the loci and/or complex interaction with life-style and metabolic parameters.

  18. Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.

    Directory of Open Access Journals (Sweden)

    Michelle Cotterchio

    Full Text Available Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk.A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry, and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants.18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted=0.04. Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007.Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.

  19. Candidate gene expression affects intramuscular fat content and fatty acid composition in pigs.

    Science.gov (United States)

    Wang, Wei; Xue, Wenda; Jin, Bangquan; Zhang, Xixia; Ma, Fei; Xu, Xiaofeng

    2013-02-01

    The objective of this study was to correlate the expression pattern of candidate genes with the intramuscular fat (IMF) content and fatty acid composition of the Longissimus dorsi muscle of Duroc × Shanzhu commercial crossbred pigs. Animals of both sexes were slaughtered at a body weight of about 90 kg. The IMF content and fatty acid composition of the Longissimus dorsi muscle were measured and correlated with candidate genes mRNA expression (AdPLA, ADRB3, LEPR, MC4R, PPARγ, PPARα, LPL, PEPCK, and SCD). Females presented higher IMF content (p < 0.05) than males. The total saturated fatty acid (SFA) in males was greater (p < 0.01), whereas the total monounsaturated fatty acid (MUFA) (p < 0.01) and polyunsaturated fatty acid (PUFA) (p < 0.05) were lower than in females. The expressions of AdPLA, MC4R, PEPCK, and SCD correlated with the IMF content (p < 0.05). AdPLA showed a positive association with MUFA and a negative association with SFA (p < 0.05). LEPR and MC4R were both positively and significantly associated with C18:3 and C20:0 (p < 0.05). PPARα and PPARγ were negatively correlated with SFA, and PPARγ was positively associated with MUFA (p < 0.05). LPL was positively associated with MUFA and negatively associated with SFA (p < 0.05). PEPCK was negatively correlated with PUFA (p < 0.05). SCD was positively associated with MUFA (p < 0.05). The revealed correlations may confirm that these candidate genes are important for fat deposition and fatty acid composition in pigs, and the evaluation and use of these genes may be useful for improving porcine meat quality. PMID:23275256

  20. Analysis of the transcriptome of Erigeron breviscapus uncovers putative scutellarin and chlorogenic acids biosynthetic genes and genetic markers.

    Directory of Open Access Journals (Sweden)

    Ni-Hao Jiang

    Full Text Available Erigeron breviscapus (Vant. Hand-Mazz. is a famous medicinal plant. Scutellarin and chlorogenic acids are the primary active components in this herb. However, the mechanisms of biosynthesis and regulation for scutellarin and chlorogenic acids in E. breviscapus are considerably unknown. In addition, genomic information of this herb is also unavailable.Using Illumina sequencing on GAIIx platform, a total of 64,605,972 raw sequencing reads were generated and assembled into 73,092 non-redundant unigenes. Among them, 44,855 unigenes (61.37% were annotated in the public databases Nr, Swiss-Prot, KEGG, and COG. The transcripts encoding the known enzymes involved in flavonoids and in chlorogenic acids biosynthesis were discovered in the Illumina dataset. Three candidate cytochrome P450 genes were discovered which might encode flavone 6-hydroase converting apigenin to scutellarein. Furthermore, 4 unigenes encoding the homologues of maize P1 (R2R3-MYB transcription factors were defined, which might regulate the biosynthesis of scutellarin. Additionally, a total of 11,077 simple sequence repeat (SSR were identified from 9,255 unigenes. Of SSRs, tri-nucleotide motifs were the most abundant motif. Thirty-six primer pairs for SSRs were randomly selected for validation of the amplification and polymorphism. The result revealed that 34 (94.40% primer pairs were successfully amplified and 19 (52.78% primer pairs exhibited polymorphisms.Using next generation sequencing (NGS technology, this study firstly provides abundant genomic data for E. breviscapus. The candidate genes involved in the biosynthesis and transcriptional regulation of scutellarin and chlorogenic acids were obtained in this study. Additionally, a plenty of genetic makers were generated by identification of SSRs, which is a powerful tool for molecular breeding and genetics applications in this herb.

  1. Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes.

    Science.gov (United States)

    Saunders, Colleen J; Jalali Sefid Dashti, Mahjoubeh; Gamieldien, Junaid

    2016-01-01

    Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation of human genes and identify candidate genes by ontology-seeded queries capturing the features of tendinopathy. Our BioOntological Relationship Graph database (BORG) integrates multiple sources of genomic and biomedical knowledge into an on-disk semantic network where human genes and their orthologs in mouse and rat are central concepts mapped to ontology terms. The BORG was used to screen all human genes for potential links to tendinopathy. Following further prioritisation, four strong candidate genes (COL11A2, ELN, ITGB3, LOX) were identified. These genes are differentially expressed in tendinopathy, functionally linked to features of tendinopathy and previously implicated in other connective tissue diseases. In conclusion, cross-domain semantic integration of multiple sources of biomedical knowledge, and interrogation of phenotypes and gene functions associated with disease, may significantly increase the probability of identifying strong and unobvious candidate genes in genetic association studies. PMID:26804977

  2. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.

    Science.gov (United States)

    Rai, Rajani; Kim, Jong Joo; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2015-01-01

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p ADRB3 rs4994 as candidate influencing GBC susceptibility. PMID:26602921

  3. Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes.

    NARCIS (Netherlands)

    Franke, L.; Bakel, H. van; Fokkens, L.; Jong, E.D. de; Egmont-Peterson, M.; Wijmenga, C.

    2006-01-01

    Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain

  4. Expression analysis of 13 ovine immune response candidate genes in Visna/Maedi disease progression.

    Science.gov (United States)

    Larruskain, Amaia; Bernales, Irantzu; Luján, Lluis; de Andrés, Damián; Amorena, Beatriz; Jugo, Begoña M

    2013-07-01

    Visna/Maedi virus (VMV) is a lentivirus that infects cells of the monocyte/macrophage lineage in sheep. Infection with VMV may lead to Visna/Maedi (VM) disease, which causes a multisystemic inflammatory disorder causing pneumonia, encephalitis, mastitis and arthritis. The role of ovine immune response genes in the development of VM disease is not fully understood. In this work, sheep of the Rasa Aragonesa breed were divided into two groups depending on the presence/absence of VM-characteristic clinical lesions in the aforementioned organs and the relative levels of candidate gene expression, including cytokines and innate immunity loci were measured by qPCR in the lung and udder. Sheep with lung lesions showed differential expression in five target genes: CCR5, TLR7, and TLR8 were up regulated and IL2 and TNFα down regulated. TNFα up regulation was detected in the udder. PMID:23582860

  5. Analysis of breast cancer metastasis candidate genes from next generation-sequencing via systematic functional genomics

    DEFF Research Database (Denmark)

    Blomstrøm, Monica Marie

    2016-01-01

    Metastatic breast cancer remains an incurable disease accounting for the vast majority of deaths from breast cancer. Understanding the molecular mechanisms for metastatic spread is important to improve diagnosis and for generating starting points for novel treatment strategies. Inhibition...... advantage of mutations is that they are most likely stable in the metastatic cancer cell population, whereas miRNA, mRNA and protein expression profiles may change substantially prior to, throughout, or after the complex metastatic process as well as between subpopulations such as cancer stem cells (CSCs......) and non-CSCs. The main goal of this project was to functionally characterize a set of candidate genes recovered from next-generation sequencing analysis for their role in breast cancer metastasis formation. The starting gene set comprised 104 gene variants; i.e. 57 wildtype and 47 mutated variants. During...

  6. Exploiting Differential Gene Expression and Epistasis to Discover Candidate Genes for Drought-Associated QTLs in Arabidopsis thaliana

    Science.gov (United States)

    Lovell, John T.; Mullen, Jack L.; Lowry, David B.; Awole, Kedija; Richards, James H.; Sen, Saunak; Verslues, Paul E.; Juenger, Thomas E.; McKay, John K.

    2015-01-01

    Soil water availability represents one of the most important selective agents for plants in nature and the single greatest abiotic determinant of agricultural productivity, yet the genetic bases of drought acclimation responses remain poorly understood. Here, we developed a systems-genetic approach to characterize quantitative trait loci (QTLs), physiological traits and genes that affect responses to soil moisture deficit in the TSUxKAS mapping population of Arabidopsis thaliana. To determine the effects of candidate genes underlying QTLs, we analyzed gene expression as a covariate within the QTL model in an effort to mechanistically link markers, RNA expression, and the phenotype. This strategy produced ranked lists of candidate genes for several drought-associated traits, including water use efficiency, growth, abscisic acid concentration (ABA), and proline concentration. As a proof of concept, we recovered known causal loci for several QTLs. For other traits, including ABA, we identified novel loci not previously associated with drought. Furthermore, we documented natural variation at two key steps in proline metabolism and demonstrated that the mitochondrial genome differentially affects genomic QTLs to influence proline accumulation. These findings demonstrate that linking genome, transcriptome, and phenotype data holds great promise to extend the utility of genetic mapping, even when QTL effects are modest or complex. PMID:25873386

  7. Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours

    Directory of Open Access Journals (Sweden)

    Xie Yi

    2009-02-01

    Full Text Available Abstract Background Recently, microRNAs (miRNAs have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics. Results In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found. Conclusion Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new

  8. Molecular Mapping and Candidate Gene Analysis for Numerous Spines on the Fruit of Cucumber.

    Science.gov (United States)

    Zhang, Shengping; Liu, Shulin; Miao, Han; Wang, Min; Liu, Panna; Wehner, Todd C; Gu, Xingfang

    2016-09-01

    Number of spines on the fruit is an important quality trait in cucumber. The inheritance and identification of molecular markers for fruit spine density gene can provide a basis for breeding and lay the foundation for gene cloning. Cucumber inbred lines NCG-122 with numerous spines and NCG-121 with few spines were used for genetic analysis and gene mapping in this study. Genetic analysis showed that the numerous spines trait in NCG-122 was qualitative, and a single recessive nuclear gene (ns) controlled this trait. The few spines trait was dominant over the numerous spines trait. In the preliminary genetic mapping of the ns gene, 8 SSR markers were found to be linked to ns, which mapped to chromosome 2 (Chr.2) of cucumber. The closest flanking markers SSR22338 and SSR11596 were linked to the ns gene, with genetic distances of 10.2 and 1.7cM, respectively. One-hundred and thirty pairs of new SSR primers and 28 pairs of Indel primers were developed based on sequence information in the preliminary mapping region of ns Fifteen SSR markers and 2 Indel markers were identified to be linked to the ns gene after analysis on the F2 mapping population using the new molecular markers. The 2 closest flanking markers, SSRns-127 and SSR04219, were 0.7 and 2.4 cM from ns, respectively. The physical distance between SSRns-127 and SSR04219 was 266.1kb, containing 27 predicted genes. Csa2G285390 was speculated as the probable candidate gene for numerous spines. The accuracy of the closest linked marker to the ns gene, SSRns-127, for MAS breeding was 95.0%. PMID:27317924

  9. Identification of candidate susceptibility genes for colorectal cancer through eQTL analysis

    Science.gov (United States)

    Closa, Adria; Cordero, David; Sanz-Pamplona, Rebeca; Solé, Xavier; Crous-Bou, Marta; Paré-Brunet, Laia; Berenguer, Antoni; Guino, Elisabet; Lopez-Doriga, Adriana; Guardiola, Jordi; Biondo, Sebastiano; Salazar, Ramon; Moreno, Victor

    2014-01-01

    In this study, we aim to identify the genes responsible for colorectal cancer risk behind the loci identified in genome-wide association studies (GWAS). These genes may be candidate targets for developing new strategies for prevention or therapy. We analyzed the association of genotypes for 26 GWAS single nucleotide polymorphisms (SNPs) with the expression of genes within a 2 Mb region (cis-eQTLs). Affymetrix Human Genome U219 expression arrays were used to assess gene expression in two series of samples, one of healthy colonic mucosa (n = 47) and other of normal mucosa adjacent to colon cancer (n = 97, total 144). Paired tumor tissues (n = 97) were also analyzed but did not provide additional findings. Partial Pearson correlation (r), adjusted for sample type, was used for the analysis. We have found Bonferroni-significant cis-eQTLs in three loci: rs3802842 in 11q23.1 associated to C11orf53, COLCA1 (C11orf92) and COLCA2 (C11orf93; r = 0.60); rs7136702 in 12q13.12 associated to DIP2B (r = 0.63) and rs5934683 in Xp22.3 associated to SHROOM2 and GPR143 (r = 0.47). For loci in chromosomes 11 and 12, we have found other SNPs in linkage disequilibrium that are more strongly associated with the expression of the identified genes and are better functional candidates: rs7130173 for 11q23.1 (r = 0.66) and rs61927768 for 12q13.12 (r = 0.86). These SNPs are located in DNA regions that may harbor enhancers or transcription factor binding sites. The analysis of trans-eQTLs has identified additional genes in these loci that may have common regulatory mechanisms as shown by the analysis of protein–protein interaction networks. PMID:24760461

  10. RNA-Seq Based Identification of Candidate Parasitism Genes of Cereal Cyst Nematode (Heterodera avenae during Incompatible Infection to Aegilops variabilis.

    Directory of Open Access Journals (Sweden)

    Minghui Zheng

    Full Text Available One of the reasons for the progressive yield decline observed in cereals production is the rapid build-up of populations of the cereal cyst nematode (CCN, Heterodera avenae. These nematodes secrete so-call effectors into their host plant to suppress the plant defense responses, alter plant signaling pathways and then induce the formation of syncytium after infection. However, little is known about its molecular mechanism and parasitism during incompatible infection. To gain insight into its repertoire of parasitism genes, we investigated the transcriptome of the early parasitic second-stage (30 hours, 3 days and 9 days post infection juveniles of the CCN as well as the CCN infected tissue of the host Aegilops variabilis by Illumina sequencing. Among all assembled unigenes, 681 putative genes of parasitic nematode were found, in which 56 putative effectors were identified, including novel pioneer genes and genes corresponding to previously reported effectors. All the 681 CCN unigenes were mapped to 229 GO terms and 200 KEGG pathways, including growth, development and several stimulus-related signaling pathways. Sixteen clusters were involved in the CCN unigene expression atlas at the early stages during infection process, and three of which were significantly gene-enriched. Besides, the protein-protein interaction network analysis revealed 35 node unigenes which may play an important role in the plant-CCN interaction. Moreover, in a comparison of differentially expressed genes between the pre-parasitic juveniles and the early parasitic juveniles, we found that hydrolase activity was up-regulated in pre J2s whereas binding activity was upregulated in infective J2s. RT-qPCR analysis on some selected genes showed detectable expression, indicating possible secretion of the proteins and putative role in infection. This study provided better insights into the incompatible interaction between H. avenae and the host plant Ae. varabilis. Moreover, RNAi

  11. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  12. Exploiting genomics resources to identify candidate genes underlying antioxidants content in tomato fruit

    Directory of Open Access Journals (Sweden)

    Roberta eCalafiore

    2016-04-01

    Full Text Available The tomato is a model species for fleshy fruit development and ripening, as well as for genomics studies of others Solanaceae. Many genetic and genomics resources, including databases for sequencing, transcriptomics and metabolomics data, have been developed and are today available. The purpose of the present work was to uncover new genes and/or alleles that determine ascorbic acid and carotenoids accumulation, by exploiting one Solanum pennellii introgression lines (IL7-3 harboring quantitative trait loci (QTL that increase the content of these metabolite in the fruit. The higher ascorbic acid and carotenoids content in IL7-3 was confirmed at three fruit developmental stages. The tomato genome reference sequence and the recently released S. pennellii genome sequence were investigated to identify candidate genes that might control ascorbic acid and carotenoids accumulation. First of all, a refinement of the wild region borders in the IL7-3 was achieved by analyzing CAPS markers designed in our laboratory. Afterwards, six candidate genes associated to ascorbic acid and one with carotenoids metabolism were identified exploring the annotation and the Gene Ontology terms of genes included in the region. Variants between the sequence of the wild and the cultivated alleles of these genes were investigated for their functional relevance and their potential effects on the protein sequences were predicted. Transcriptional levels of candidate genes in the introgression region were extracted from RNA-Seq data available for the entire S. pennellii introgression lines collection and verified by Real-Time qPCR. Finally, seven IL7-3 sub-lines were genotyped using 28 species-specific markers and then were evaluated for metabolites content. These analyses evidenced a significant decrease in transcript abundance for one 9-cis-epoxycarotenoid dioxygenase and one L-ascorbate oxidase homolog, whose role in the accumulation of carotenoids and ascorbic acid is

  13. Construction of a gene bank and use of the chromosome walking technique for the detection of new putative agrocin genes in Agrobacterium tumefaciens strain D286

    International Nuclear Information System (INIS)

    A gene bank of Agrobacterium tumefaciens D286 wt has been constructed by cloning D286 wt DNA partially digested with EcoRI in the cosmid vector pLAFRI. The library; composed of 1750 members with a 27.7 kb average insert size was probed with pCDTn5-3, a cosmid vector carrying a D286:: Tn5 insert from the strain D286:: Tn5 Ag-. One recombinant cosmid of the library, pCDO932, was detected. The insert DNA of pCDO932 has sequences homologous to the D286:: Tn5 insert of pCDTn5-3, therefore it carries putative wt agrocin D286 genes. The insert DNA of pCDO932 was isolated and used to probe the D286 wt gene library. Chromosome walking resulted in the detection of pCD2375. EcoRI restriction digestions and DNA homology studies of pCDO932 and pCD2375 showed that their D286 wt inserts are both composed of 4 EcoRI DNA sub-fragments totalling 21.8 and 24.8 kb respectively, with an overlapping sequence extending 3.5 kb. In order to overcome the failure to detect A. tumefaciens cells transformed with pCDO932. Vectors pSUP204-1 was constructed. Such vector has been derived from pSUP204 which were slightly altered by cloning into it a 700 bp λ DNA SalI fragmet. This resulted in insertion inactivation of the Tcr gene, allows the use of pSUP204-1 as a subcloning vector in conjugations and transformations involving pCDO932 or pCD2375 and strains D286:: Tn5 Ag- and C58 C1G. Two recombinant cosmids bearing D286 wt DNA inserts, at least one of which (pCDO932) contains DNA sequences putatively affecting agrocin D286 production, are now available for further genetic manipulations. pSUP204-1 should prove useful as a subcloning vector for transformations and conjugations involving recombinant cosmids from the D286 wt gene bank and Agrobacterium strains. Future work on the molecular biology of agrocin D286 production is discussed. The DNA probe used in this study was labelled with phosphorus 32

  14. Computational analysis of candidate disease genes and variants for Salt-sensitive hypertension in indigenous Southern Africans

    KAUST Repository

    Tiffin, Nicki

    2010-09-27

    Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension. © 2010 Tiffin et al.

  15. Meta-analysis and candidate gene mining of low-phosphorus tolerance in maize

    Institute of Scientific and Technical Information of China (English)

    Hongwei Zhang; Mohammed Shalim Uddin; Cheng Zou; Chuanxiao Xie; Yunbi Xu; WenXue Li

    2014-01-01

    Plants with tolerance to low-phosphorus (P) can grow better under low-P conditions, and understanding of genetic mechanisms of low-P tolerance can not only facilitate identifying relevant genes but also help to develop low-P tolerant cultivars. QTL meta-analysis was conducted after a comprehensive review of the reports on QTL mapping for low-P tolerance-related traits in maize. Meta-analysis pro-duced 23 consensus QTL (cQTL), 17 of which located in similar chromosome regions to those previously reported to influence root traits. Meanwhile, candidate gene mining yielded 215 genes, 22 of which located in the cQTL regions. These 22 genes are homologous to 14 functionally character-ized genes that were found to participate in plant low-P tolerance, including genes encoding miR399s, Pi transporters and purple acid phosphatases. Four cQTL loci (cQTL2-1, cQTL5-3, cQTL6-2, and cQTL10-2) may play important roles for low-P tolerance because each contains more original QTL and has better consistency across previous reports.

  16. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  17. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    Directory of Open Access Journals (Sweden)

    Ubadah Sabbagh

    2016-01-01

    Full Text Available The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES. A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  18. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study. PMID:27088090

  19. Identification of the candidate genes associated with cellular rejection in pig-to-human xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To identify the genes associated with cellular rejection in pig-to-human xenotransplantation, the suppression subtractive hybridization (SSH) was used in screening the up-regulated genes from a co-culture of human peripheral blood mononuclear cells (PBMCs) and porcine vascular endothelial cell line PIEC. The up-regulated cDNAs were cloned into pGEM-T Easy vector and then sequenced. Nucleic acid homology searches were performed using the BLAST program. A subtracted cDNA library including about 300 clones with the expected up-regulated genes was obtained. Twenty-four of these clones were analyzed by sequencing and homology comparison was made. These clones represent the genes of human perforin (PRF1), proteasome, lymphocyte specific interferon regulatory factor/interferon regulatory factor 4 (LSIRF/IRF 4), muscleblind-like (MBNL) protein and a porcine expressed sequence tag (EST) which has 81% homology with human oxidative-stress responsive 1 (OSR 1). These genes might be the candidate genes which are associated with cellular rejection in pig-to-human xenotransplantation.

  20. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

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    Reusch Thorsten BH

    2011-01-01

    Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  1. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene

    Directory of Open Access Journals (Sweden)

    Herington Adrian C

    2008-10-01

    Full Text Available Abstract Background The peptide hormone ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH release, appetite regulation, gut motility and proliferation of cancer cells. We previously identified a gene on the opposite strand of the ghrelin gene, ghrelinOS (GHRLOS, which spans the promoter and untranslated regions of the ghrelin gene (GHRL. Here we further characterise GHRLOS. Results We have described GHRLOS mRNA isoforms that extend over 1.4 kb of the promoter region and 106 nucleotides of exon 4 of the ghrelin gene, GHRL. These GHRLOS transcripts initiate 4.8 kb downstream of the terminal exon 4 of GHRL and are present in the 3' untranslated exon of the adjacent gene TATDN2 (TatD DNase domain containing 2. Interestingly, we have also identified a putative non-coding TATDN2-GHRLOS chimaeric transcript, indicating that GHRLOS RNA biogenesis is extremely complex. Moreover, we have discovered that the 3' region of GHRLOS is also antisense, in a tail-to-tail fashion to a novel terminal exon of the neighbouring SEC13 gene, which is important in protein transport. Sequence analyses revealed that GHRLOS is riddled with stop codons, and that there is little nucleotide and amino-acid sequence conservation of the GHRLOS gene between vertebrates. The gene spans 44 kb on 3p25.3, is extensively spliced and harbours multiple variable exons. We have also investigated the expression of GHRLOS and found evidence of differential tissue expression. It is highly expressed in tissues which are emerging as major sites of non-coding RNA expression (the thymus, brain, and testis, as well as in the ovary and uterus. In contrast, very low levels were found in the stomach where sense, GHRL derived RNAs are highly expressed. Conclusion GHRLOS RNA transcripts display several distinctive features of non-coding (ncRNA genes, including 5' capping, polyadenylation, extensive splicing and short open reading

  2. Genomic analysis of differentiation between soil types reveals candidate genes for local adaptation in Arabidopsis lyrata.

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    Thomas L Turner

    Full Text Available Serpentine soil, which is naturally high in heavy metal content and has low calcium to magnesium ratios, comprises a difficult environment for most plants. An impressive number of species are endemic to serpentine, and a wide range of non-endemic plant taxa have been shown to be locally adapted to these soils. Locating genomic polymorphisms which are differentiated between serpentine and non-serpentine populations would provide candidate loci for serpentine adaptation. We have used the Arabidopsis thaliana tiling array, which has 2.85 million probes throughout the genome, to measure genetic differentiation between populations of Arabidopsis lyrata growing on granitic soils and those growing on serpentinic soils. The significant overrepresentation of genes involved in ion transport and other functions provides a starting point for investigating the molecular basis of adaptation to soil ion content, water retention, and other ecologically and economically important variables. One gene in particular, calcium-exchanger 7, appears to be an excellent candidate gene for adaptation to low CaratioMg ratio in A. lyrata.

  3. Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

    Directory of Open Access Journals (Sweden)

    Kathiravan Periasamy

    Full Text Available Sheep chromosome 3 (Oar3 has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05 in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have

  4. Candidate Gene Approach for Parasite Resistance in Sheep – Variation in Immune Pathway Genes and Association with Fecal Egg Count

    Science.gov (United States)

    Periasamy, Kathiravan; Pichler, Rudolf; Poli, Mario; Cristel, Silvina; Cetrá, Bibiana; Medus, Daniel; Basar, Muladno; A. K., Thiruvenkadan; Ramasamy, Saravanan; Ellahi, Masroor Babbar; Mohammed, Faruque; Teneva, Atanaska; Shamsuddin, Mohammed; Podesta, Mario Garcia; Diallo, Adama

    2014-01-01

    Sheep chromosome 3 (Oar3) has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs) within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF) did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05) in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have potential for

  5. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

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    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  6. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha;

    2015-01-01

    associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (Pfunctional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage...

  7. Harvesting candidate genes responsible for serious adverse drug reactions from a chemical-protein interactome.

    Directory of Open Access Journals (Sweden)

    Lun Yang

    2009-07-01

    Full Text Available Identifying genetic factors responsible for serious adverse drug reaction (SADR is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might share a common mechanism by targeting unexpectedly the same SADR-mediating protein. Hence we propose an approach of identifying the common SADR-targets through constructing and mining an in silico chemical-protein interactome (CPI, a matrix of binding strengths among 162 drug molecules known to cause at least one type of SADR and 845 proteins. Drugs sharing the same SADR outcome were also found to possess similarities in their CPI profiles towards this 845 protein set. This methodology identified the candidate gene of sulfonamide-induced toxic epidermal necrolysis (TEN: all nine sulfonamides that cause TEN were found to bind strongly to MHC I (Cw*4, whereas none of the 17 control drugs that do not cause TEN were found to bind to it. Through an insight into the CPI, we found the Y116S substitution of MHC I (B*5703 enhances the unexpected binding of abacavir to its antigen presentation groove, which explains why B*5701, not B*5703, is the risk allele of abacavir-induced hypersensitivity. In conclusion, SADR targets and the patient-specific off-targets could be identified through a systematic investigation of the CPI, generating important hypotheses for prospective experimental validation of the candidate genes.

  8. Dynamic QTL analysis and candidate gene mapping for waterlogging tolerance at maize seedling stage.

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    Khalid A Osman

    Full Text Available Soil waterlogging is one of the major abiotic stresses adversely affecting maize growth and yield. To identify dynamic expression of genes or quantitative trait loci (QTL, QTL associated with plant height, root length, root dry weight, shoot dry weight and total dry weight were identified via conditional analysis in a mixed linear model and inclusive composite interval mapping method at three respective periods under waterlogging and control conditions. A total of 13, 19 and 23 QTL were detected at stages 3D|0D (the period during 0-3 d of waterlogging, 6D|3D and 9D|6D, respectively. The effects of each QTL were moderate and distributed over nine chromosomes, singly explaining 4.14-18.88% of the phenotypic variation. Six QTL (ph6-1, rl1-2, sdw4-1, sdw7-1, tdw4-1 and tdw7-1 were identified at two consistent stages of seedling development, which could reflect a continuous expression of genes; the remaining QTL were detected at only one stage. Thus, expression of most QTL was influenced by the developmental status. In order to provide additional evidence regarding the role of corresponding genes in waterlogging tolerance, mapping of Expressed Sequence Tags markers and microRNAs were conducted. Seven candidate genes were observed to co-localize with the identified QTL on chromosomes 1, 4, 6, 7 and 9, and may be important candidate genes for waterlogging tolerance. These results are a good starting point for understanding the genetic basis for selectively expressing of QTL in different stress periods and the common genetic control mechanism of the co-localized traits.

  9. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

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    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  10. Expression studies of the obesity candidate gene FTO in pig

    DEFF Research Database (Denmark)

    Madsen, Majbritt Busk; Birck, Malene Muusfeldt; Fredholm, Merete;

    2010-01-01

    Obesity is an increasing problem worldwide and research on candidate genes in good animal models is highly needed. The pig is an excellent model as its metabolism, organ size, and eating habits resemble that of humans. The present study is focused on the characterization of the fat mass and obesi...... compared with cerebellum of the high-cholesterol fed pigs. Furthermore, SNPs were investigated in the coding sequence of the FTO in the Gottingen minipig and in the Danish commercial pig. Eleven synonymous SNPs and a two bp insertion were found between the two pig lines....

  11. The Genetic Basis of Quality of Life in Healthy Swedish Women: A Candidate Gene Approach

    OpenAIRE

    Dounya Schoormans; Jingmei Li; Hatef Darabi; Yvonne Brandberg; Sprangers, Mirjam A. G.; Mikael Eriksson; Zwinderman, Koos H.; Per Hall

    2015-01-01

    Background Quality of life (QoL) is an increasingly important parameter in clinical practice as it predicts mortality and poor health outcomes. It is hypothesized that one may have a genetic predisposition for QoL. We therefore related 139 candidate genes, selected through a literature search, to QoL in healthy females. Methods In 5,142 healthy females, background characteristics (i.e. demographic, clinical, lifestyle, and psychological factors) were assessed. QoL was measured by the EORTC QL...

  12. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers

    OpenAIRE

    Qi, Chao; Zhu, Yiwei Tony; Hu, Liping; Zhu, Yi-Jun

    2009-01-01

    Fat, a candidate tumor suppressor in drosophila, is a component of Hippo signaling pathway involved in controlling organ size. We found that a ~3Mbp deletion in mouse chromosome 3 caused tumorigenesis of a non-tumorigenic mammary epithelial cell line. The expression of Fat4 gene, one member of the Fat family, in the deleted region was inactivated, which resulted from promoter methylation of another Fat4 allele following the deletion of one Fat4 allele. Re-expression of Fat4 in Fat4-deficient ...

  13. Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes

    OpenAIRE

    Colleen J. Saunders; Mahjoubeh Jalali Sefid Dashti; Junaid Gamieldien

    2016-01-01

    Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation...

  14. Evaluation of the porcine ACSL4 gene as a candidate gene for meat quality traits in pigs.

    Science.gov (United States)

    Corominas, J; Ramayo-Caldas, Y; Castelló, A; Muñoz, M; Ibáñez-Escriche, N; Folch, J M; Ballester, M

    2012-12-01

    Long-chain acyl-CoA synthetase (ACSL) family members catalyse the formation of long-chain acyl-CoA from fatty acid, ATP and CoA, thus playing an important role in both de novo lipid synthesis and fatty acid catabolism. Previous studies in our group evaluated ACSL4 as a positional candidate gene for quantitative trait loci located on chromosome X in an Iberian × Landrace cross. A DQ144454:c.2645G>A SNP located in the 3' untranslated region of the ACSL4 gene was associated with the percentages of oleic and monounsaturated fatty acids. The aim of the present work was to evaluate the functional implication of this genetic variant. An expression analysis was performed for 120 individuals with different genotypes for the DQ144454:c.2645G>A polymorphism using real-time quantitative PCR. Differences between genotypes were identified in liver, with the ACSL4 mRNA expression levels higher in animals with the G allele than in animals with the A allele. A SNP genome-wide association study with ACSL4 relative expression levels showed significant positions on chromosomes 6 and 12. Description of positional candidate genes for ACSL4 regulation on chromosomes 6 and 12 is provided.

  15. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

    Directory of Open Access Journals (Sweden)

    van Oost Bernard A

    2007-10-01

    Full Text Available Abstract Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

  16. Association Studies of 3 Candidate Genes with Type 2 Diabetes Mellitus in a Chinese Population

    Institute of Scientific and Technical Information of China (English)

    鲁一兵; 缪珩; 王华; 何戎华; 马立隽; 金卫新; 华子春

    2002-01-01

    Objectives To explore the relationship between the polymorphisms of the select-ed short tandem repeats (STRs) of the candidate genes and type 2 diabetes mellitus (DM) in a Chinesepopulation, the role of genetic and environmental factors in the development of type 2 diabetes. Meth-ods STRs including D11S916 of uncoupling protein 3 (UCP3) gene,binucleotide repeat (CA). with-in intron 6 [HSLi6 (CA)n] of hormone- sensitive lipase(HSL) gene and D20S501 of protein tyrosinephosphatase- 1B (PTP-1B) gene polymorphisms were detected by polymerase chain reaction (PCR) , poly-acrylamiie gel electrophoresis and silver staining in 106 patients with type 2 DM and 102 control sub-jects. Results The allele distribution of UCP3 and HSL gene differed significantly between patientswith type 2 diabetes and control subjects (χ2 = 26. 12, P<0.005; χ2=10. 33, P<0. 005, respec-tively). For UCP3 and HSL gene,the frequencies of alleles A6,A7 ,A8 and allele B9 were much high-er in diabetic patients than in control subjects (0. 090 vs 0. 020,P<0. 005; 0. 109 vs 0. 015,P<0. 005; 0. 033 υs 0. 000,P<0.05; 0. 033 υs 0. 005,P<0. 05,respectively),while the fre-quencies of allele A1 and allele B5 were lower in diabetic patients than in control subjects (0. 090 vs0. 206,P<0. 005; 0. 057 vs 0. 118,P<0. 05,respectively). At D20S501 locus,The allele dis-tribution of PTP-1B gene had no significant difference in two groups (χ2=3. 77 ,P>0. 05). Multi-variate logistic regression analysis showed positive correlation between alleles A 6,A 7 of UCP3 gene,sys-tolic blood pressure , apolipoprotein B , lipoprotein (a) and type 2 diabetes. Conclusion Our datashow that D11S916 of UCP3 gene and HSLi6 (CA), of HSL gene polymorphisms are associated withtype 2 diabetes in Chinese suggesting that UCP3 and HSL might represent susceptibility genes for type 2diabetes. D20S501 of PTP-1B gene polymorphism isnot associated uith type 2 diabetes in Chinese. AllelesA6, A7 of UCP3 gene, systolic blood

  17. Identification of candidate target genes of pituitary adenomas based on the DNA microarray.

    Science.gov (United States)

    Zhou, Wei; Ma, Chun-Xiao; Xing, Ya-Zhou; Yan, Zhao-Yue

    2016-03-01

    The present study aimed to explore molecular mechanisms involved in pituitary adenomas (PAs) and to discover target genes for their treatment. The gene expression profile GSE4488 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the Limma package and analyzed by two‑dimensional hierarchical clustering. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions of DEGs. Subsequently, the protein‑protein interaction (PPI) network was constructed using Cytoscape software. DEGs were then mapped to the connectivity map database to identify molecular agents associated with the underlying mechanisms of PAs. A total of 340 upregulated and 49 downregulated DEGs in PA samples compared with those in normal controls were identified. Hierarchical clustering analysis showed that DEGs were highly differentially expressed, indicating their aptness for distinguishing PA samples from normal controls. Significant gene ontology terms were positive regulation of immune system-associated processes for downregulated DEGs and skeletal system development for upregulated DEGs. Pathways significantly enriched by DEGs included extracellular matrix (ECM)‑receptor interaction, the Hedgehog (Hh) signaling pathway and neuroactive ligand‑receptor interaction. The PPI network was constructed with 117 nodes, 123 edges and CD44 and Gli2 as hub nodes. Furthermore, depudecin, a small molecule drug, was identified to be mechanistically associated with PA. The genes CD44 and Gli2 have important roles in the progression of PAs via ECM‑receptor interaction and the Hh signaling pathway and are therefore potential target genes of PA. In addition, depudecin may be a candidate drug for the treatment of PAs. PMID:26782791

  18. Identification of the gene encoding Brain Cell Membrane Protein 1 (BCMP1, a putative four-transmembrane protein distantly related to the Peripheral Myelin Protein 22 / Epithelial Membrane Proteins and the Claudins

    Directory of Open Access Journals (Sweden)

    Christophe Daniel

    2001-07-01

    Full Text Available Abstract Background A partial cDNA clone from dog thyroid presenting a very significant similarity with an uncharacterized mouse EST sequence was isolated fortuitously. We report here the identification of the complete mRNA and of the gene, the product of which was termed "brain cell membrane protein 1" (BCMP1. Results The 4 kb-long mRNA sequence exhibited an open-reading frame of only 543 b followed by a 3.2 kb-long 3' untranslated region containing several AUUUA instability motifs. Analysis of the encoded protein sequence identified the presence of four putative transmembrane domains. Similarity searches in protein domain databases identified partial sequence conservations with peripheral myelin protein 22 (PMP22/ epithelial membrane proteins (EMPs and Claudins, defining the encoded protein as representative of the existence of a novel subclass in this protein family. Northern-blot analysis of the expression of the corresponding mRNA in adult dog tissues revealed the presence of a huge amount of the 4 kb transcript in the brain. An EGFP-BCMP1 fusion protein expressed in transfected COS-7 cells exhibited a membranous localization as expected. The sequences encoding BCMP1 were assigned to chromosome X in dog, man and rat using radiation hybrid panels and were partly localized in the currently available human genome sequence. Conclusions We have identified the existence in several mammalian species of a gene encoding a putative four-transmembrane protein, BCMP1, wich defines a novel subclass in this family of proteins. In dog at least, the corresponding mRNA is highly present in brain cells. The chromosomal localization of the gene in man makes of it a likely candidate gene for X-linked mental retardation.

  19. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    Directory of Open Access Journals (Sweden)

    Duy Ngoc Do

    2014-09-01

    Full Text Available Residual feed intake (RFI is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs, candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2 and 60k genotypic data was used. Genome-wide association analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as XIRP2, TTC29, SOGA1, MAS1, GRK5, PROX1, GPR155 and ZFYVE26 were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kilo base pairs of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2 were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher’s exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05. These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs.

  20. Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis.

    Science.gov (United States)

    Mahalakshmi, Natarajan; Aparnaa, Ramanathan; Ansel Vishal, Lawrance; Kaliraj, Perumal

    2013-09-01

    Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks. One of the extensively studied vaccine candidates is abundant larval transcripts (ALT) family of proteins for the following properties: highly regulated expression, abundance, excreted-secreted product of infective stage larvae, and essentially for parasite establishment and survival in the host. In the present study, stage-specific expression of secreted larval acidic protein 1 (SLAP1) was identified; an ALT orthologue from Onchocerca volvulus was cloned, expressed, and purified as a recombinant protein. Immunogenicity of OvSLAP1 was demonstrated with sera and peripheral blood mononuclear cells from endemic regions of Brugia malayi and Wuchereria bancrofti. OvSLAP1 antibodies were predominated by IgG1 and IgG2 in endemic normal (EN) and chronic pathology (CP) subjects. It has also induced marked cellular response as observed by lymphoproliferation assay. The study revealed that OvSLAP1 can segregate humoral (EN mean optical density (OD) = 0.87 ± 0.035, CP mean OD = 0.59 ± 0.029) and cellular (EN mean stimulation index (SI) = 5.87 ± 0.167, CP mean SI = 3.5 ± 0.134) immune responses between EN and CP individuals (P < 0.001), signifying its prophylactic ability and vitality for protection from filarial infections in endemic population. PMID:23828189

  1. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

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    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  2. Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12

    OpenAIRE

    Kobayashi, Misato; Suzuki, Miyako; Ohno, Tamio; Tsuzuki, Kana; Taguchi, Chie; Tateishi, Soushi; Kawada, Teruo; Kim, Young-Il; Murai, Atsushi; Horio, Fumihiko

    2016-01-01

    Background The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was identified in a SM/J × SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is a fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-12SM consomic mice. The aim of this study was to identify candidate genes for Fl1sa, and to invest...

  3. Association and mutation analyses of 16p11.2 autism candidate genes.

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    Ravinesh A Kumar

    Full Text Available BACKGROUND: Autism is a complex childhood neurodevelopmental disorder with a strong genetic basis. Microdeletion or duplication of a approximately 500-700-kb genomic rearrangement on 16p11.2 that contains 24 genes represents the second most frequent chromosomal disorder associated with autism. The role of common and rare 16p11.2 sequence variants in autism etiology is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To identify common 16p11.2 variants with a potential role in autism, we performed association studies using existing data generated from three microarray platforms: Affymetrix 5.0 (777 families, Illumina 550 K (943 families, and Affymetrix 500 K (60 families. No common variants were identified that were significantly associated with autism. To look for rare variants, we performed resequencing of coding and promoter regions for eight candidate genes selected based on their known expression patterns and functions. In total, we identified 26 novel variants in autism: 13 exonic (nine non-synonymous, three synonymous, and one untranslated region and 13 promoter variants. We found a significant association between autism and a coding variant in the seizure-related gene SEZ6L2 (12/1106 autism vs. 3/1161 controls; p = 0.018. Sez6l2 expression in mouse embryos was restricted to the spinal cord and brain. SEZ6L2 expression in human fetal brain was highest in post-mitotic cortical layers, hippocampus, amygdala, and thalamus. Association analysis of SEZ6L2 in an independent sample set failed to replicate our initial findings. CONCLUSIONS/SIGNIFICANCE: We have identified sequence variation in at least one candidate gene in 16p11.2 that may represent a novel genetic risk factor for autism. However, further studies are required to substantiate these preliminary findings.

  4. Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study

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    Reinthal Eva

    2009-09-01

    Full Text Available Abstract Background Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population. Methods Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin, RDX (radixin, SNX16 (sorting nexin 16, OPA1 (optic atrophy 1, MFN1 (mitofusin 1, MFN2 (mitofusin 2, PARL (presenilin associated, rhomboid-like, SOD2 (superoxide dismutase 2, mitochondrial and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1. These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing. Results Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1 is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes. Conclusion Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.

  5. Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression network analyses

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    Lionikas Arimantas

    2012-11-01

    Full Text Available Abstract Background We have recently identified a number of Quantitative Trait Loci (QTL contributing to the 2-fold muscle weight difference between the LG/J and SM/J mouse strains and refined their confidence intervals. To facilitate nomination of the candidate genes responsible for these differences we examined the transcriptome of the tibialis anterior (TA muscle of each strain by RNA-Seq. Results 13,726 genes were expressed in mouse skeletal muscle. Intersection of a set of 1061 differentially expressed transcripts with a mouse muscle Bayesian Network identified a coherent set of differentially expressed genes that we term the LG/J and SM/J Regulatory Network (LSRN. The integration of the QTL, transcriptome and the network analyses identified eight key drivers of the LSRN (Kdr, Plbd1, Mgp, Fah, Prss23, 2310014F06Rik, Grtp1, Stk10 residing within five QTL regions, which were either polymorphic or differentially expressed between the two strains and are strong candidates for quantitative trait genes (QTGs underlying muscle mass. The insight gained from network analysis including the ability to make testable predictions is illustrated by annotating the LSRN with knowledge-based signatures and showing that the SM/J state of the network corresponds to a more oxidative state. We validated this prediction by NADH tetrazolium reductase staining in the TA muscle revealing higher oxidative potential of the SM/J compared to the LG/J strain (p Conclusion Thus, integration of fine resolution QTL mapping, RNA-Seq transcriptome information and mouse muscle Bayesian Network analysis provides a novel and unbiased strategy for nomination of muscle QTGs.

  6. Candidate genes of Waldenström’s macroglobulinemia: current evidence and research

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    Bianchi G

    2013-07-01

    Full Text Available Giada Bianchi,1 Antonio Sacco,1 Shaji Kumar,2 Giuseppe Rossi,3 Irene Ghobrial,1 Aldo Roccaro11Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Department of Hematology, Spedali Civili di Brescia, Brescia, ItalyAbstract: Waldenström’s macroglobulinemia (WM is a relatively uncommon, indolent malignancy of immunoglobulin M-producing B cells. The World Health Organization classifies it as a lymphoplasmacytic lymphoma and patients typically present with anemia, hepatosplenomegaly and diffuse lymphadenopathies. Historically, the genetic characterization of the disease has been hampered by the relatively low proliferative rate of WM cells, thus making karyotyping challenging. The use of novel technologies such as fluorescence in situ hybridization, gene array, and whole genome sequencing has contributed greatly to establishing candidate genes in the pathophysiology of WM and to identifying potential treatment targets, such as L265P MYD88. The discovery of microRNAs and the recognition of epigenetics as a major modulatory mechanism of oncogene expression and/or oncosuppressor silencing have aided in further understanding the pathogenesis of WM. Once thought to closely resemble multiple myeloma, a cancer of terminally differentiated, immunoglobulin-secreting plasma cells, WM appears to genetically cluster with other indolent B-cell lymphomas such as chronic lymphocytic leukemia/small cell lymphoma. The relative high incidence of familial cases of WM and other B-cell malignancies has been helpful in identifying high-risk gene candidates. In this review, we focus on the established genes involved in the pathogenesis of WM, with special emphasis on the key role of derangement of the nuclear factor kappa B signaling pathway and epigenetic mechanisms.Keywords: genetics, familial cases, NF-κB, whole genome sequencing, MYD88

  7. Molecular characterization of two candidate genes associated with coat color in Tibetan sheep (Ovis arise)

    Institute of Scientific and Technical Information of China (English)

    HAN Ji-long; YANG Min; GUO Ting-ting; YUE Yao-jing; LIU Jian-bin; NIU Chun-e; WANG Chao-feng; YANG Bo-hui

    2015-01-01

    Coat color is a key economic trait in sheep. Some candidate genes associated with animal’s coat color were found. Partic-ularly, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and microphthalmia-associated transcription factor (MITF) play a key role in the modulation of hair pigmentation in mammals. This study investigated those two candidate genes’ mutations and expressions associated with wool color in Tibetan sheep. First, the gene polymorphisms of those two genes were analyzed, and then, relative mRNA expression levels of those two genes in skin tissue with different coat colors were compared. Thirdly, KIT and MITF protein expression levels were detected through Western blot and immune-histochemical. Al ele C was predominant al ele in the white coat color Tibetan sheep population of the MITF coding region g. 1548 C/T loci. The relative MITF mRNA expression in black coat skin tissue was signiifcantly higher than white (P0.05), while the level of KIT protein expression in skin tissues of white and black coats was also roughly equivalent. Our study observed that, the level of MITF protein expression in black coat skin tissue was signiifcantly higher than that in white coat skin tissue, and positive staining for MITF protein expression was detected mainly in the epidermis and the dermal papil a, bulb, and outer root sheath of hair fol icles. We conclude that the black coat of Tibetan sheep is related to high MITF expression in the hair fol icles, and MITF may be important for coat color formation of Tibetan sheep.

  8. An LTR Retrotransposon-Derived Gene Displays Lineage-Specific Structural and Putative Species-Specific Functional Variations in Eutherians.

    Science.gov (United States)

    Irie, Masahito; Koga, Akihiko; Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2016-01-01

    Amongst the 11 eutherian-specific genes acquired from a sushi-ichi retrotransposon is the CCHC type zinc-finger protein-encoding gene SIRH11/ZCCHC16. Its contribution to eutherian brain evolution is implied because of its involvement in cognitive function in mice, possibly via the noradrenergic system. Although, the possibility that Sirh11/Zcchc16 functions as a non-coding RNA still remains, dN/dS ratios in pairwise comparisons between its orthologs have provided supportive evidence that it acts as a protein. It became a pseudogene in armadillos (Cingulata) and sloths (Pilosa), the only two extant orders of xenarthra, which prompted us to examine the lineage-specific variations of SIRH11/ZCCHC16 in eutherians. We examined the predicted SIRH11/ZCCHC16 open reading frame (ORF) in 95 eutherian species based on the genomic DNA information in GenBank. A large variation in the SIRH11/ZCCHC16 ORF was detected in several lineages. These include a lack of a CCHC RNA-binding domain in its C-terminus, observed in gibbons (Hylobatidae: Primates) and megabats (Megachiroptera: Chiroptera). A lack of the N-terminal half, on the other hand, was observed in New World monkeys (Platyrrhini: Primates) and species belonging to New World and African Hystricognaths (Caviomorpha and Bathyergidae: Rodents) along with Cetacea and Ruminantia (Cetartiodactyla). Among the hominoids, interestingly, three out of four genera of gibbons have lost normal SIRH11/ZCCHC16 function by deletion or the lack of the CCHC RNA-binding domain. Our extensive dN/dS analysis suggests that such truncated SIRH11/ZCCHC16 ORFs are functionally diversified even within lineages. Combined, our results show that SIRH11/ZCCHC16 may contribute to the diversification of eutherians by lineage-specific structural changes after its domestication in the common eutherian ancestor, followed by putative species-specific functional changes that enhanced fitness and occurred as a consequence of complex natural selection events

  9. A candidate gene association study on muscat flavor in grapevine (Vitis vinifera L.

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    Boursiquot Jean-Michel

    2010-11-01

    Full Text Available Abstract Background The sweet, floral flavor typical of Muscat varieties (Muscats, due to high levels of monoterpenoids (geraniol, linalool and nerol, is highly distinct and has been greatly appreciated both in table grapes and in wine since ancient times. Muscat flavor determination in grape (Vitis vinifera L. has up to now been studied by evaluating monoterpenoid levels through QTL analysis. These studies have revealed co-localization of 1-deoxy-D-xylulose 5-phosphate synthase (VvDXS with the major QTL positioned on chromosome 5. Results We resequenced VvDXS in an ad hoc association population of 148 grape varieties, which included muscat-flavored, aromatic and neutral accessions as well as muscat-like aromatic mutants and non-aromatic offsprings of Muscats. Gene nucleotide diversity and intragenic linkage disequilibrium (LD were evaluated. Structured association analysis revealed three SNPs in moderate LD to be significantly associated with muscat-flavored varieties. We identified a putative causal SNP responsible for a predicted non-neutral substitution and we discuss its possible implications for flavor metabolism. Network analysis revealed a major star-shaped cluster of reconstructed haplotypes unique to muscat-flavored varieties. Moreover, muscat-like aromatic mutants displayed unique non-synonymous mutations near the mutated site of Muscat genotypes. Conclusions This study is a crucial step forward in understanding the genetic regulation of muscat flavor in grapevine and it also sheds light on the domestication history of Muscats. VvDXS appears to be a possible human-selected locus in grapevine domestication and post-domestication. The putative causal SNP identified in Muscat varieties as well as the unique mutations identifying the muscat-like aromatic mutants under study may be immediately applied in marker-assisted breeding programs aimed at enhancing fragrance and aroma complexity respectively in table grape and wine cultivars.

  10. Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

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    Chenet Stella M

    2012-03-01

    Full Text Available Abstract Background A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP, Duffy-binding protein (DBP, Merozoite surface protein-1 (MSP-1, Apical membrane antigen-1 (AMA-1 and Thrombospondin related anonymous protein (TRAP. Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity.

  11. Association study of candidate gene polymorphisms with amnestic mild cognitive impairment in a Chinese population.

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    Xiaoyan Liu

    Full Text Available To investigate the relationship between amnestic mild cognitive impairment (aMCI and candidate gene polymorphisms in a Chinese population, 116 aMCI patients and 93 normal controls were recruited. Multi-dimensional neuropsychological tests were used to extensively assess the cognitive functions of the subjects. MassARRAY and iPLEX systems were used to measure candidate single nucleotide polymorohisms (SNPs and analyse allelic, genotypic or haplotypic distributions. The scores of the neuropsychological tests were significantly lower for the aMCI patients than for the normal controls. The distributions of SNPs relating to the amyloid cascade hypothesis (TOMM40 rs157581 G and TOMM40 rs2075650 G, to the cholesterol metabolism hypothesis (ApoE rs429358 C, LDLR rs11668477 G and CH25H rs7091822 T and PLAU rs2227564 CT and to the tau hypothesis (MAPT/STH rs242562 GG in aMCI were significantly different than those in normal controls. Interactions were also found in aMCI amongst SNPs in LDLR rs11668477, PLAU rs2227564, and TOMM40 rs157581, between SNPs in TOMM40 rs157580 and BACE2 rs9975138. The study suggests that aMCI is characterised by memory impairment and associated with SNPs in three systems relating to the pathogenesis of AD--those of the amyloid cascade, tau and cholesterol metabolism pathways. Interactions were also observed between genes in the amyloid pathway and between the amyloid and cholesterol pathways.

  12. Transcriptome analysis reveals candidate genes involved in luciferin metabolism in Luciola aquatilis (Coleoptera: Lampyridae)

    Science.gov (United States)

    Vongsangnak, Wanwipa; Chumnanpuen, Pramote

    2016-01-01

    Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system. PMID:27761329

  13. Comparative inter-strain sequence analysis of the putative regulatory region of murine psychostimulant-regulated gene GNB1 (G protein beta 1 subunit gene).

    Science.gov (United States)

    Kitanaka, Nobue; Kitanaka, Junichi; Walther, Donna; Wang, Xiao-Bing; Uhl, George R

    2003-08-01

    We isolated a cDNA clone from a murine genomic library of C57BL/6 strain, carrying 13.8 kb of nucleotides including exon 1 of heterotrimeric GTP-binding protein beta 1 subunit gene (genetic symbol, GNB1) and 10.6 kb of the 5' flanking region. Sequence comparison with GNB1 gene locus from 129Sv strain revealed a 0.2% divergence in a 13.2 kb common region between these two strains. The divergence consisted of eight single nucleotide polymorphisms, three insertions and one deletion, with 129Sv used as the reference. The exon 1 and the putative regulation elements, such as cyclic AMP response element, AP1, AP2, Sp1 and nuclear factor-kappa B recognition sites, were perfectly conserved. The expression of GNB1 mRNA was significantly increased in mouse striatum 2 h after single methamphetamine administration with an approximately 150% expression level compared with the basal level. In contrast, no change in the expression level was observed in the cerebral cortex. After the chronic methamphetamine treatment regimen, the expression level of GNB1 mRNA did not change in any brain regions examined. These results suggest (1) that the 5' flanking nucleotide sequence of GNB1 gene was strictly conserved for its possible contribution to the same change in the expression level between the mouse strains in response to psychostimulants and (2) that the initial process of development of behavioral sensitization appeared to occur parallel to the significant increase in the expression level of GNB1 gene in the mouse striatum. PMID:14631649

  14. A candidate-gene association study for berry colour and anthocyanin content in Vitis vinifera L.

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    Silvana Cardoso

    Full Text Available Anthocyanin content is a trait of major interest in Vitis vinifera L. These compounds affect grape and wine quality, and have beneficial effects on human health. A candidate-gene approach was used to identify genetic variants associated with anthocyanin content in grape berries. A total of 445 polymorphisms were identified in 5 genes encoding transcription factors and 10 genes involved in either the biosynthetic pathway or transport of anthocyanins. A total of 124 SNPs were selected to examine association with a wide range of phenotypes based on RP-HPLC analysis and visual characterization. The phenotypes were total skin anthocyanin (TSA concentration but also specific types of anthocyanins and relative abundance. The visual assessment was based on OIV (Organisation Internationale de la Vigne et du Vin descriptors for berry and skin colour. The genes encoding the transcription factors MYB11, MYBCC and MYC(B were significantly associated with TSA concentration. UFGT and MRP were associated with several different types of anthocyanins. Skin and pulp colour were associated with nine genes (MYB11, MYBCC, MYC(B, UFGT, MRP, DFR, LDOX, CHI and GST. Pulp colour was associated with a similar group of 11 genes (MYB11, MYBCC, MYC(B, MYC(A, UFGT, MRP, GST, DFR, LDOX, CHI and CHS(A. Statistical interactions were observed between SNPs within the transcription factors MYB11, MYBCC and MYC(B. SNPs within LDOX interacted with MYB11 and MYC(B, while SNPs within CHI interacted with MYB11 only. Together, these findings suggest the involvement of these genes in anthocyanin content and on the regulation of anthocyanin biosynthesis. This work forms a benchmark for replication and functional studies.

  15. Screening for Genes Coding for Putative Antitumor Compounds, Antimicrobial and Enzymatic Activities from Haloalkalitolerant and Haloalkaliphilic Bacteria Strains of Algerian Sahara Soils

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    Okba Selama

    2014-01-01

    Full Text Available Extreme environments may often contain unusual bacterial groups whose physiology is distinct from those of normal environments. To satisfy the need for new bioactive pharmaceuticals compounds and enzymes, we report here the isolation of novel bacteria from an extreme environment. Thirteen selected haloalkalitolerant and haloalkaliphilic bacteria were isolated from Algerian Sahara Desert soils. These isolates were screened for the presence of genes coding for putative antitumor compounds using PCR based methods. Enzymatic, antibacterial, and antifungal activities were determined by using cultural dependant methods. Several of these isolates are typical of desert and alkaline saline soils, but, in addition, we report for the first time the presence of a potential new member of the genus Nocardia with particular activity against the yeast Saccharomyces cerevisiae. In addition to their haloalkali character, the presence of genes coding for putative antitumor compounds, combined with the antimicrobial activity against a broad range of indicator strains and their enzymatic potential, makes them suitable for biotechnology applications.

  16. Identification of multipath genes differentially expressed in pathway-targeted microarrays in zebrafish infected and surviving spring viremia carp virus (SVCV suggest preventive drug candidates.

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    Paloma Encinas

    Full Text Available Spring viremia carp virus (SVCV is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG. The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a

  17. The tep1 gene of Sinorhizobium meliloti coding for a putative transmembrane efflux protein and N-acetyl glucosamine affect nod gene expression and nodulation of alfalfa plants

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    Soto María

    2009-01-01

    Full Text Available Abstract Background Soil bacteria collectively known as Rhizobium, characterized by their ability to establish beneficial symbiosis with legumes, share several common characteristics with pathogenic bacteria when infecting the host plant. Recently, it was demonstrated that a fadD mutant of Sinorhizobium meliloti is altered in the control of swarming, a type of co-ordinated movement previously associated with pathogenicity, and is also impaired in nodulation efficiency on alfalfa roots. In the phytopathogen Xanthomonas campestris, a fadD homolog (rpfB forms part of a cluster of genes involved in the regulation of pathogenicity factors. In this work, we have investigated the role in swarming and symbiosis of SMc02161, a S. meliloti fadD-linked gene. Results The SMc02161 locus in S. meliloti shows similarities with members of the Major Facilitator Superfamily (MFS of transporters. A S. meliloti null-mutant shows increased sensitivity to chloramphenicol. This indication led us to rename the locus tep1 for transmembrane efflux protein. The lack of tep1 does not affect the appearance of swarming motility. Interestingly, nodule formation efficiency on alfalfa plants is improved in the tep1 mutant during the first days of the interaction though nod gene expression is lower than in the wild type strain. Curiously, a nodC mutation or the addition of N-acetyl glucosamine to the wild type strain lead to similar reductions in nod gene expression as in the tep1 mutant. Moreover, aminosugar precursors of Nod factors inhibit nodulation. Conclusion tep1 putatively encodes a transmembrane protein which can confer chloramphenicol resistance in S. meliloti by expelling the antibiotic outside the bacteria. The improved nodulation of alfalfa but reduced nod gene expression observed in the tep1 mutant suggests that Tep1 transports compounds which influence nodulation. In contrast to Bradyrhizobium japonicum, we show that in S. meliloti there is no feedback regulation

  18. Next-generation sequencing for identification of candidate genes for Fusarium wilt and sterility mosaic disease in pigeonpea (Cajanus cajan).

    Science.gov (United States)

    Singh, Vikas K; Khan, Aamir W; Saxena, Rachit K; Kumar, Vinay; Kale, Sandip M; Sinha, Pallavi; Chitikineni, Annapurna; Pazhamala, Lekha T; Garg, Vanika; Sharma, Mamta; Sameer Kumar, Chanda Venkata; Parupalli, Swathi; Vechalapu, Suryanarayana; Patil, Suyash; Muniswamy, Sonnappa; Ghanta, Anuradha; Yamini, Kalinati Narasimhan; Dharmaraj, Pallavi Subbanna; Varshney, Rajeev K

    2016-05-01

    To map resistance genes for Fusarium wilt (FW) and sterility mosaic disease (SMD) in pigeonpea, sequencing-based bulked segregant analysis (Seq-BSA) was used. Resistant (R) and susceptible (S) bulks from the extreme recombinant inbred lines of ICPL 20096 × ICPL 332 were sequenced. Subsequently, SNP index was calculated between R- and S-bulks with the help of draft genome sequence and reference-guided assembly of ICPL 20096 (resistant parent). Seq-BSA has provided seven candidate SNPs for FW and SMD resistance in pigeonpea. In parallel, four additional genotypes were re-sequenced and their combined analysis with R- and S-bulks has provided a total of 8362 nonsynonymous (ns) SNPs. Of 8362 nsSNPs, 60 were found within the 2-Mb flanking regions of seven candidate SNPs identified through Seq-BSA. Haplotype analysis narrowed down to eight nsSNPs in seven genes. These eight nsSNPs were further validated by re-sequencing 11 genotypes that are resistant and susceptible to FW and SMD. This analysis revealed association of four candidate nsSNPs in four genes with FW resistance and four candidate nsSNPs in three genes with SMD resistance. Further, In silico protein analysis and expression profiling identified two most promising candidate genes namely C.cajan_01839 for SMD resistance and C.cajan_03203 for FW resistance. Identified candidate genomic regions/SNPs will be useful for genomics-assisted breeding in pigeonpea. PMID:26397045

  19. Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings.

    Science.gov (United States)

    Mondal, M; Sengupta, M; Samanta, S; Sil, A; Ray, K

    2012-12-15

    Albinism represents a group of genetic disorders with a broad spectrum of hypopigmentary phenotypes dependent on the genetic background of the patients. Oculocutaneous albinism (OCA) patients have little or no pigment in their eyes, skin and hair, whereas ocular albinism (OA) primarily presents the ocular symptoms, and the skin and hair color may vary from near normal to very fair. Mutations in genes directly or indirectly regulating melanin production are responsible for different forms of albinism with overlapping clinical features. In this study, 27 albinistic individuals from 24 families were screened for causal variants by a PCR-sequencing based approach. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, TYRP2 and SILV were selected as candidate genes. We identified 5 TYR and 3 OCA2 mutations, majority in homozygous state, in 8 unrelated patients including a case of autosomal recessive ocular albinism (AROA). A homozygous 4-nucleotide novel insertion in SLC24A5 was detected in a person showing with extreme cutaneous hypopigmentation. A potential causal variant was identified in the TYRP2 gene in a single patient. Haplotype analyses in the patients carrying homozygous mutations in the classical OCA genes suggested founder effect. This is the first report of an Indian AROA patient harboring a mutation in OCA2. Our results also reveal for the first time that mutations in SLC24A5 could contribute to extreme hypopigmentation in humans.

  20. Identification of putative chemosensory receptor genes from yellow peach moth Conogethes punctiferalis (Guenée) antennae transcriptome

    Science.gov (United States)

    Ge, Xing; Zhang, Tiantao; Wang, Zhenying; He, Kanglai; Bai, Shuxiong

    2016-01-01

    The yellow peach moth, Conogethes punctiferalis, is an extremely important polyphagous insect in Asia. The chemosensory systems of moth play an important role in detecting food, oviposition sites and mate attraction. Several antennal chemosensory receptors are involved in odor detection. Our study aims to identify chemosensory receptor genes for potential applications in behavioral responses of yellow peach moth. By transcriptomic analysis of male and female antennae, 83 candidate chemosensory receptors, including 62 odorant receptors, 11 ionotropic receptors and 10 gustatory receptors were identified. Through Blast and sequence alignment, the highly conserved co-receptor Orco was annotated, eight unigenes clustered into pheromone receptors, and two clustered as sugar receptor. Among the IRs, one unigenes was similar with co-receptors IR25a. Expression levels of 50 odorant receptors were further evaluated by quantitative real-time PCR in antennae. All the ORs tested were detected in antennae and some of which were associated with sex-biased expression. The chemosensory receptors identified in C. punctiferalis provide a foundational resource for further analysis on olfaction for behavior. The expression profiles of ORs in antennae indicated variant functions in olfactory recognition, and our results provided the possibility for the potential application of semiochemical to control this pest moth. PMID:27659493

  1. Identification of candidate genes for familial early-onset essential tremor.

    Science.gov (United States)

    Liu, Xinmin; Hernandez, Nora; Kisselev, Sergey; Floratos, Aris; Sawle, Ashley; Ionita-Laza, Iuliana; Ottman, Ruth; Louis, Elan D; Clark, Lorraine N

    2016-07-01

    Essential tremor (ET) is one of the most common causes of tremor in humans. Despite its high heritability and prevalence, few susceptibility genes for ET have been identified. To identify ET genes, whole-exome sequencing was performed in 37 early-onset ET families with an autosomal-dominant inheritance pattern. We identified candidate genes for follow-up functional studies in five ET families. In two independent families, we identified variants predicted to affect function in the nitric oxide (NO) synthase 3 gene (NOS3) that cosegregated with disease. NOS3 is highly expressed in the central nervous system (including cerebellum), neurons and endothelial cells, and is one of three enzymes that converts l-arginine to the neurotransmitter NO. In one family, a heterozygous variant, c.46G>A (p.(Gly16Ser)), in NOS3, was identified in three affected ET cases and was absent in an unaffected family member; and in a second family, a heterozygous variant, c.164C>T (p.(Pro55Leu)), was identified in three affected ET cases (dizygotic twins and their mother). Both variants result in amino-acid substitutions of highly conserved amino-acid residues that are predicted to be deleterious and damaging by in silico analysis. In three independent families, variants predicted to affect function were also identified in other genes, including KCNS2 (KV9.2), HAPLN4 (BRAL2) and USP46. These genes are highly expressed in the cerebellum and Purkinje cells, and influence function of the gamma-amino butyric acid (GABA)-ergic system. This is in concordance with recent evidence that the pathophysiological process in ET involves cerebellar dysfunction and possibly cerebellar degeneration with a reduction in Purkinje cells, and a decrease in GABA-ergic tone. PMID:26508575

  2. Identification of Arabidopsis candidate genes in response to biotic and abiotic stresses using comparative microarrays.

    Directory of Open Access Journals (Sweden)

    Arjun Sham

    Full Text Available Plants have evolved with intricate mechanisms to cope with multiple environmental stresses. To adapt with biotic and abiotic stresses, plant responses involve changes at the cellular and molecular levels. The current study was designed to investigate the effects of combinations of different environmental stresses on the transcriptome level of Arabidopsis genome using public microarray databases. We investigated the role of cyclopentenones in mediating plant responses to environmental stress through TGA (TGACG motif-binding factor transcription factor, independently from jasmonic acid. Candidate genes were identified by comparing plants inoculated with Botrytis cinerea or treated with heat, salt or osmotic stress with non-inoculated or non-treated tissues. About 2.5% heat-, 19% salinity- and 41% osmotic stress-induced genes were commonly upregulated by B. cinerea-treatment; and 7.6%, 19% and 48% of genes were commonly downregulated by B. cinerea-treatment, respectively. Our results indicate that plant responses to biotic and abiotic stresses are mediated by several common regulatory genes. Comparisons between transcriptome data from Arabidopsis stressed-plants support our hypothesis that some molecular and biological processes involved in biotic and abiotic stress response are conserved. Thirteen of the common regulated genes to abiotic and biotic stresses were studied in detail to determine their role in plant resistance to B. cinerea. Moreover, a T-DNA insertion mutant of the Responsive to Dehydration gene (rd20, encoding for a member of the caleosin (lipid surface protein family, showed an enhanced sensitivity to B. cinerea infection and drought. Overall, the overlapping of plant responses to abiotic and biotic stresses, coupled with the sensitivity of the rd20 mutant, may provide new interesting programs for increased plant resistance to multiple environmental stresses, and ultimately increases its chances to survive. Future research

  3. Copy number variants in candidate genes are genetic modifiers of Hirschsprung disease.

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    Qian Jiang

    Full Text Available Hirschsprung disease (HSCR is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. The HSCR phenotype is highly variable with respect to gender, length of aganglionosis, familiality and the presence of additional anomalies. By molecular genetic analysis, a minimum of 11 neuro-developmental genes (RET, GDNF, NRTN, SOX10, EDNRB, EDN3, ECE1, ZFHX1B, PHOX2B, KIAA1279, TCF4 are known to harbor rare, high-penetrance mutations that confer a large risk to the bearer. In addition, two other genes (RET, NRG1 harbor common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. To broaden this search, we examined whether a set of 67 proven and candidate HSCR genes harbored additional modifier alleles. In this pilot study, we utilized a custom-designed array CGH with ∼33,000 test probes at an average resolution of ∼185 bp to detect gene-sized or smaller copy number variants (CNVs within these 67 genes in 18 heterogeneous HSCR patients. Using stringent criteria, we identified CNVs at three loci (MAPK10, ZFHX1B, SOX2 that are novel, involve regulatory and coding sequences of neuro-developmental genes, and show association with HSCR in combination with other congenital anomalies. Additional CNVs are observed under relaxed criteria. Our research suggests a role for CNVs in HSCR and, importantly, emphasizes the role of variation in regulatory sequences. A much larger study will be necessary both for replication and for identifying the full spectrum of small CNV effects.

  4. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

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    Sofie Claerhout

    Full Text Available BACKGROUND: Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. CONCLUSIONS/SIGNIFICANCE: We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

  5. A combination of transcriptome and methylation analyses reveals embryologically-relevant candidate genes in MRKH patients

    Directory of Open Access Journals (Sweden)

    Riess Olaf

    2011-05-01

    Full Text Available Abstract Background The Mayer-Rokitansky-Küster-Hauser (MRKH syndrome is present in at least 1 out of 4,500 female live births and is the second most common cause for primary amenorrhea. It is characterized by vaginal and uterine aplasia in an XX individual with normal secondary characteristics. It has long been considered a sporadic anomaly, but familial clustering occurs. Several candidate genes have been studied although no single factor has yet been identified. Cases of discordant monozygotic twins suggest that the involvement of epigenetic factors is more likely. Methods Differences in gene expression and methylation patterns of uterine tissue between eight MRKH patients and eight controls were identified using whole-genome microarray analyses. Results obtained by expression and methylation arrays were confirmed by qRT-PCR and pyrosequencing. Results We delineated 293 differentially expressed and 194 differentially methylated genes of which nine overlap in both groups. These nine genes are mainly embryologically relevant for the development of the female genital tract. Conclusion Our study used, for the first time, a combined whole-genome expression and methylation approach to reveal the etiology of the MRKH syndrome. The findings suggest that either deficient estrogen receptors or the ectopic expression of certain HOXA genes might lead to abnormal development of the female reproductive tract. In utero exposure to endocrine disruptors or abnormally high maternal hormone levels might cause ectopic expression or anterior transformation of HOXA genes. It is, however, also possible that different factors influence the anti-Mullerian hormone promoter activity during embryological development causing regression of the Müllerian ducts. Thus, our data stimulate new research directions to decipher the pathogenic basis of MRKH syndrome.

  6. Genome-wide and candidate gene association study of cigarette smoking behaviors.

    Directory of Open Access Journals (Sweden)

    Neil Caporaso

    Full Text Available The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO Trial, and 2,282 women from the Nurses' Health Study (NHS. We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years, and three binary (ever versus never smoking, 10 cigarettes per day [CPDBI], and current versus former smoking. Association testing for each single nucleotide polymorphism (SNP was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10(-7 in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10(-5 for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10(-3, including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4x10(-5, our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.

  7. Identification of Quantitative Trait Loci (QTL) and Candidate Genes for Cadmium Tolerance in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Induri, Brahma R [West Virginia University; Ellis, Danielle R [West Virginia University; Slavov, Gancho [West Virginia University; Yin, Tongming [ORNL; Muchero, Wellington [ORNL; Tuskan, Gerald A [ORNL; DiFazio, Stephen P [West Virginia University

    2012-01-01

    Knowledge of genetic variation in response of Populus to heavy metals like cadmium (Cd) is an important step in understanding the underlying mechanisms of tolerance. In this study, a pseudo-backcross pedigree of Populus trichocarpa and Populus deltoides was characterized for Cd exposure. The pedigree showed significant variation for Cd tolerance thus enabling the identification of relatively tolerant and susceptible genotypes for intensive characterization. A total of 16 QTLs at logarithm of odds (LOD) ratio > 2.5, were found to be associated with total dry weight, its components, and root volume. Four major QTLs for total dry weight were mapped to different linkage groups in control (LG III) and Cd conditions (LG XVI) and had opposite allelic effects on Cd tolerance, suggesting that these genomic regions were differentially controlled. The phenotypic variation explained by Cd QTL for all traits under study varied from 5.9% to 11.6% and averaged 8.2% across all QTL. Leaf Cd contents also showed significant variation suggesting the phytoextraction potential of Populus genotypes, though heritability of this trait was low (0.22). A whole-genome microarray study was conducted by using two genotypes with extreme responses for Cd tolerance in the above study and differentially expressed genes were identified. Candidate genes including CAD2 (CADMIUM SENSITIVE 2), HMA5 (HEAVY METAL ATPase5), ATGTST1 (Arabidopsis thaliana Glutathione S-Transferase1), ATGPX6 (Glutathione peroxidase 6), and ATMRP 14 (Arabidopsis thaliana Multidrug Resistance associated Protein 14) were identified from QTL intervals and microarray study. Functional characterization of these candidate genes could enhance phytoremediation capabilities of Populus.

  8. Mosaic zebrafish transgenesis for functional genomic analysis of candidate cooperative genes in tumor pathogenesis.

    Science.gov (United States)

    Ung, Choong Yong; Guo, Feng; Zhang, Xiaoling; Zhu, Zhihui; Zhu, Shizhen

    2015-01-01

    Comprehensive genomic analysis has uncovered surprisingly large numbers of genetic alterations in various types of cancers. To robustly and efficiently identify oncogenic "drivers" among these tumors and define their complex relationships with concurrent genetic alterations during tumor pathogenesis remains a daunting task. Recently, zebrafish have emerged as an important animal model for studying human diseases, largely because of their ease of maintenance, high fecundity, obvious advantages for in vivo imaging, high conservation of oncogenes and their molecular pathways, susceptibility to tumorigenesis and, most importantly, the availability of transgenic techniques suitable for use in the fish. Transgenic zebrafish models of cancer have been widely used to dissect oncogenic pathways in diverse tumor types. However, developing a stable transgenic fish model is both tedious and time-consuming, and it is even more difficult and more time-consuming to dissect the cooperation of multiple genes in disease pathogenesis using this approach, which requires the generation of multiple transgenic lines with overexpression of the individual genes of interest followed by complicated breeding of these stable transgenic lines. Hence, use of a mosaic transient transgenic approach in zebrafish offers unique advantages for functional genomic analysis in vivo. Briefly, candidate transgenes can be coinjected into one-cell-stage wild-type or transgenic zebrafish embryos and allowed to integrate together into each somatic cell in a mosaic pattern that leads to mixed genotypes in the same primarily injected animal. This permits one to investigate in a faster and less expensive manner whether and how the candidate genes can collaborate with each other to drive tumorigenesis. By transient overexpression of activated ALK in the transgenic fish overexpressing MYCN, we demonstrate here the cooperation of these two oncogenes in the pathogenesis of a pediatric cancer, neuroblastoma that has

  9. Validation of putative reference genes for qRT-PCR normalization in tissues and blood from pigs infected with Actinobacillus pleuropneumoniae

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Poulsen, K.T.;

    2007-01-01

    from sample to sample. In the present study, six putative reference genes were validated for normalization of gene expression in three different tissues and in white blood cells from pigs experimentally infected with the common respiratory pathogen Actinobacillus pleuropneumoniae. Two dedicated...... validation programs (geNorm and Normfinder) were used to rank the six reference genes from best to worst. qRT-PCR data for the proinflammatory cytokine IL-6 was normalized using the proposed genes from geNorm and Normfinder as well as the commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase...... to non-infected control animals with a good agreement of expression differences between the two programs. On the contrary, normalization of IL-6 expression data from blood using GAPDH rendered the difference between infected and non-infected groups non-significant, and resulted in significantly different...

  10. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia.

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    Katariina Hannula-Jouppi

    2005-10-01

    Full Text Available Dyslexia, or specific reading disability, is the most common learning disorder with a complex, partially genetic basis, but its biochemical mechanisms remain poorly understood. A locus on Chromosome 3, DYX5, has been linked to dyslexia in one large family and speech-sound disorder in a subset of small families. We found that the axon guidance receptor gene ROBO1, orthologous to the Drosophila roundabout gene, is disrupted by a chromosome translocation in a dyslexic individual. In a large pedigree with 21 dyslexic individuals genetically linked to a specific haplotype of ROBO1 (not found in any other chromosomes in our samples, the expression of ROBO1 from this haplotype was absent or attenuated in affected individuals. Sequencing of ROBO1 in apes revealed multiple coding differences, and the selection pressure was significantly different between the human, chimpanzee, and gorilla branch as compared to orangutan. We also identified novel exons and splice variants of ROBO1 that may explain the apparent phenotypic differences between human and mouse in heterozygous loss of ROBO1. We conclude that dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans.

  11. The Axon Guidance Receptor Gene ROBO1 Is a Candidate Gene for Developmental Dyslexia.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Dyslexia, or specific reading disability, is the most common learning disorder with a complex, partially genetic basis, but its biochemical mechanisms remain poorly understood. A locus on Chromosome 3, DYX5, has been linked to dyslexia in one large family and speech-sound disorder in a subset of small families. We found that the axon guidance receptor gene ROBO1, orthologous to the Drosophila roundabout gene, is disrupted by a chromosome translocation in a dyslexic individual. In a large pedigree with 21 dyslexic individuals genetically linked to a specific haplotype of ROBO1 (not found in any other chromosomes in our samples, the expression of ROBO1 from this haplotype was absent or attenuated in affected individuals. Sequencing of ROBO1 in apes revealed multiple coding differences, and the selection pressure was significantly different between the human, chimpanzee, and gorilla branch as compared to orangutan. We also identified novel exons and splice variants of ROBO1 that may explain the apparent phenotypic differences between human and mouse in heterozygous loss of ROBO1. We conclude that dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans.

  12. Testing candidate genes for attention-deficit/hyperactivity disorder in fruit flies using a high throughput assay for complex behavior

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Madsen, Lisbeth Strøm; Arvidson, Sandra Marie Neumann;

    2016-01-01

    Fruit flies are important model organisms for functional testing of candidate genes in multiple disciplines, including the study of human diseases. Here we use a high-throughput locomotor activity assay to test the response on activity behavior of gene disruption in Drosophila melanogaster. The a...

  13. aThe dyslexia candidate gene DYX1C1 is a potential marker of poor survival in breast cancer

    International Nuclear Information System (INIS)

    The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer. DYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox) model. DYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to any of the variables linked with mRNA expression. We show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer

  14. Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean.

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    Andrew J Burt

    Full Text Available Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris. Alleles at the Co-4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08 where Co-4 is localized. Three SCAR markers with known linkage to Co-4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK-4 loci found in previous studies. It is possible that the Co-4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases.

  15. Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean

    Science.gov (United States)

    Burt, Andrew J.; William, H. Manilal; Perry, Gregory; Khanal, Raja; Pauls, K. Peter; Kelly, James D.; Navabi, Alireza

    2015-01-01

    Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris). Alleles at the Co–4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08) where Co–4 is localized. Three SCAR markers with known linkage to Co–4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK–4 loci found in previous studies. It is possible that the Co–4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases. PMID:26431031

  16. Cell number regulator genes in Prunus provide candidate genes for the control of fruit size in sweet and sour cherry.

    Science.gov (United States)

    De Franceschi, P; Stegmeir, T; Cabrera, A; van der Knaap, E; Rosyara, U R; Sebolt, A M; Dondini, L; Dirlewanger, E; Quero-Garcia, J; Campoy, J A; Iezzoni, A F

    2013-01-01

    Striking increases in fruit size distinguish cultivated descendants from small-fruited wild progenitors for fleshy fruited species such as Solanum lycopersicum (tomato) and Prunus spp. (peach, cherry, plum, and apricot). The first fruit weight gene identified as a result of domestication and selection was the tomato FW2.2 gene. Members of the FW2.2 gene family in corn (Zea mays) have been named CNR (Cell Number Regulator) and two of them exert their effect on organ size by modulating cell number. Due to the critical roles of FW2.2/CNR genes in regulating cell number and organ size, this family provides an excellent source of candidates for fruit size genes in other domesticated species, such as those found in the Prunus genus. A total of 23 FW2.2/CNR family members were identified in the peach genome, spanning the eight Prunus chromosomes. Two of these CNRs were located within confidence intervals of major quantitative trait loci (QTL) previously discovered on linkage groups 2 and 6 in sweet cherry (Prunus avium), named PavCNR12 and PavCNR20, respectively. An analysis of haplotype, sequence, segregation and association with fruit size strongly supports a role of PavCNR12 in the sweet cherry linkage group 2 fruit size QTL, and this QTL is also likely present in sour cherry (P. cerasus). The finding that the increase in fleshy fruit size in both tomato and cherry associated with domestication may be due to changes in members of a common ancestral gene family supports the notion that similar phenotypic changes exhibited by independently domesticated taxa may have a common genetic basis. PMID:23976873

  17. Identification of candidate target genes for human peripheral arterial disease using weighted gene co‑expression network analysis.

    Science.gov (United States)

    Yin, De-Xin; Zhao, Hao-Min; Sun, Da-Jun; Yao, Jian; Ding, Da-Yong

    2015-12-01

    The aim of the present study was to identify the potential treatment targets of peripheral arterial disease (PAD) and provide further insights into the underlying mechanism of PAD, based on a weighted gene co‑expression network analysis (WGCNA) method. The mRNA expression profiles (accession. no. GSE27034), which included 19 samples from patients with PAD and 18 samples from normal control individuals were extracted from the Gene Expression Omnibus database. Subsequently, the differentially expressed genes (DEGs) were obtained using the Limma package and the co‑expression network modules were screened using the WGCNA approach. In addition, the protein‑protein interaction network for the DEGs in the most significant module was constructed using Cytoscape software. Functional enrichment analyses of the DEGs in the most significant module were also performed using the Database for Annotation, Visualization and Integrated Discovery and Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology‑Based Annotation System, respectively. A total of 148 DEGs were identified in PAD, which were used to construct the WGCN, in which two modules (gray module and turquoise module) were identified, with the gray module exhibiting a higher gene significance (GS) value than the turquoise module. In addition, a co‑expression network was constructed for 60 DEGs in the gray module. The functional enrichment results showed that the DEGs in the gray module were enriched in five Gene Ontology terms and four KEGG pathways. For example, cyclin‑dependent kinase inhibitor 1A (CDKN1A), FBJ murine osteosarcoma viral oncogene homolog (FOS) and prostaglandin‑endoperoxide synthase 2 (PTGS2) were enriched in response to glucocorticoid stimulus. The results of the present study suggested that DEGs in the gray module, including CDKN1A, FOS and PTGS2, may be associated with the pathogenesis of PAD, by modulating the cell cycle, and may offer potential for use as candidate treatment

  18. Identification of candidate genes in Populus cell wall biosynthesis using text-mining, co-expression network and comparative genomics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Bisaria, Anjali [ORNL; Tuskan, Gerald A [ORNL; Kalluri, Udaya C [ORNL

    2011-01-01

    Populus is an important bioenergy crop for bioethanol production. A greater understanding of cell wall biosynthesis processes is critical in reducing biomass recalcitrance, a major hindrance in efficient generation of ethanol from lignocellulosic biomass. Here, we report the identification of candidate cell wall biosynthesis genes through the development and application of a novel bioinformatics pipeline. As a first step, via text-mining of PubMed publications, we obtained 121 Arabidopsis genes that had the experimental evidences supporting their involvement in cell wall biosynthesis or remodeling. The 121 genes were then used as bait genes to query an Arabidopsis co-expression database and additional genes were identified as neighbors of the bait genes in the network, increasing the number of genes to 548. The 548 Arabidopsis genes were then used to re-query the Arabidopsis co-expression database and re-construct a network that captured additional network neighbors, expanding to a total of 694 genes. The 694 Arabidopsis genes were computationally divided into 22 clusters. Queries of the Populus genome using the Arabidopsis genes revealed 817 Populus orthologs. Functional analysis of gene ontology and tissue-specific gene expression indicated that these Arabidopsis and Populus genes are high likelihood candidates for functional genomics in relation to cell wall biosynthesis.

  19. A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

    Science.gov (United States)

    Morton, Nicholas M.; Nelson, Yvonne B.; Michailidou, Zoi; Di Rollo, Emma M.; Ramage, Lynne; Hadoke, Patrick W. F.; Seckl, Jonathan R.; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J.; Dunbar, Donald R.

    2011-01-01

    Background Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. Results To enrich for adipose tissue obesity genes a ‘snap-shot’ pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. Conclusions A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes

  20. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

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    Nicholas M Morton

    Full Text Available BACKGROUND: Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L strain. RESULTS: To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney was performed. Known obesity quantitative trait loci (QTL information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. CONCLUSIONS: A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue

  1. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

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    Montserrat García-Closas

    2007-02-01

    Full Text Available Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5. To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651 were associated with increased risk for bladder cancer: odds ratio (95% confidence interval: 2.52 (1.06-5.97, 2.74 (1.26-5.98, and 3.02 (1.36-6.63, respectively; and a polymorphism in intron 2 (rs3024994 was associated with reduced risk: 0.65 (0.46-0.91. Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively. These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

  2. Candidate Gene Discovery Procedure after Follow-Up Confirmatory Analyses of Candidate Regions of Interests for Alzheimer’s Disease in the NIMH Sibling Dataset

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    Tesfaye M. Baye

    2008-01-01

    Full Text Available The objective of this research was to develop a procedure to identify candidate genes under linkage peaks confirmed in a follow-up of candidate regions of interests (CRIs identified in our original genome scan in the NIMH Alzheimer’s diseases (AD Initiative families (Blacker et al. [1]. There were six CRIs identified that met the threshold of multipoint lod score (MLS of ≥ 2.0 from the original scan. The most significant peak (MLS = 7.7 was at 19q13, which was attributed to APOE. The remaining CRIs with ‘suggestive’ evidence for linkage were identified at 9q22, 6q27, 14q22, 11q25, and 3p26. We have followed up and narrowed the 9q22 CRI signal using simple tandem repeat (STR markers (Perry et al. [2]. In this confirmatory project, we have followed up the 6q27, 14q22, 11q25, and 3p26 CRIs with a total of 24 additional flanking STRs, reducing the mean interval marker distance (MID in each CRI, and substantially increase in the information content (IC. The linkage signals at 6q27, 14q22 and 11q25 remain ‘suggestive’, indicating that these CRIs are promising and worthy of detailed fine mapping and assessment of candidate genes associated with AD.

  3. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

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    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  4. Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1.

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    Jie Lu

    Full Text Available Neuroblastoma (NB is the most common extra-cranial solid tumor in children and the most frequently diagnosed cancer in the first year of life. Previous genome-wide association studies (GWAS of Caucasian and African populations have shown that common single nucleotide polymorphisms (SNPs in several genes are associated with the risk of developing NB, while few studies have been performed on Chinese children. Herein, we examined the association between the genetic polymorphisms in candidate genes and the risk of NB in Chinese children. In total, 127 SNPs in nine target genes, revealed by GWAS studies of other ethnic groups and four related lincRNAs, were genotyped in 549 samples (244 NB patients and 305 healthy controls. After adjustment for gender and age, there were 21 SNPs associated with NB risk at the two-sided P < 0.05 level, 11 of which were located in LMO1. After correction for multiple comparisons, only rs204926 in LMO1 remained significantly different between cases and controls (OR = 0.45, 95% CI: 0.31-0.65, adjusted P = 0.003. In addition, 16 haplotypes in four separate genes were significantly different between case and control groups at an unadjusted P value < 0.05, 11 of which were located in LMO1. A major haplotype, ATC, containing rs204926, rs110420, and rs110419, conferred a significant increase in risk for NB (OR = 1.82, 95% CI: 1.41-2.36, adjusted P < 0.001. The major finding of our study was obtained for risk alleles within the LMO1 gene. Our data suggest that genetic variants in LMO1 are associated with increased NB risk in Chinese children.

  5. Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1

    Science.gov (United States)

    Wang, Huanmin; Jin, Yaqiong; Han, Shujing; Han, Wei; Tai, Jun; Guo, Yongli; Ni, Xin

    2015-01-01

    Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and the most frequently diagnosed cancer in the first year of life. Previous genome-wide association studies (GWAS) of Caucasian and African populations have shown that common single nucleotide polymorphisms (SNPs) in several genes are associated with the risk of developing NB, while few studies have been performed on Chinese children. Herein, we examined the association between the genetic polymorphisms in candidate genes and the risk of NB in Chinese children. In total, 127 SNPs in nine target genes, revealed by GWAS studies of other ethnic groups and four related lincRNAs, were genotyped in 549 samples (244 NB patients and 305 healthy controls). After adjustment for gender and age, there were 21 SNPs associated with NB risk at the two-sided P < 0.05 level, 11 of which were located in LMO1. After correction for multiple comparisons, only rs204926 in LMO1 remained significantly different between cases and controls (OR = 0.45, 95% CI: 0.31–0.65, adjusted P = 0.003). In addition, 16 haplotypes in four separate genes were significantly different between case and control groups at an unadjusted P value < 0.05, 11 of which were located in LMO1. A major haplotype, ATC, containing rs204926, rs110420, and rs110419, conferred a significant increase in risk for NB (OR = 1.82, 95% CI: 1.41–2.36, adjusted P < 0.001). The major finding of our study was obtained for risk alleles within the LMO1 gene. Our data suggest that genetic variants in LMO1 are associated with increased NB risk in Chinese children. PMID:26030754

  6. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

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    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  7. Exclusion of candidate genes in a family with arterial tortuosity syndrome.

    Science.gov (United States)

    Gardella, Rita; Zoppi, Nicoletta; Assanelli, Deodato; Muiesan, Maria Lorenza; Barlati, Sergio; Colombi, Marina

    2004-04-30

    Arterial tortuosity syndrome (ATS) is a rare hereditary disorder with variable clinical presentation including tortuosity and elongation of the major arteries, often associated with pulmonary artery stenosis, pulmonary hypertension, and skin and joint laxity, suggestive of a connective tissue disorder. ATS is transmitted in an autosomal recessive mode, but the causal gene is unknown. We report an Italian pedigree with three inbred families in which five patients show signs of ATS. In particular, four adult patients present arterial tortuosity and elongation of the main arteries. Two of these patients, with the most severe degree of arterial tortuosity, also show severe peripheral stenosis of the main pulmonary artery. The fifth young patient shows a severe pulmonary valve stenosis in the absence of arterial tortuosity. All patients show signs of Ehlers-Danlos syndrome (EDS): soft skin with abundant subcutaneous tissue and joint laxity, hernias, and disorganization of the extracellular matrix (ECM) of fibronectin (FN) and of actin microfilaments in cultured skin fibroblasts. Linkage analysis of the genes involved in EDS and other connective tissue disorders, excluded COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, ADAMTS2, ELN, FN1, TNXA, and TNXB as candidate genes in the family under study, thus indicating that ATS is a distinct clinical and molecular entity. PMID:15054833

  8. Identification of candidate SNPs for drug induced toxicity from differentially expressed genes in associated tissues.

    Science.gov (United States)

    Hasmats, Johanna; Kupershmidt, Ilya; Rodríguez-Antona, Cristina; Su, Qiaojuan Jane; Khan, Muhammad Suleman; Jara, Carlos; Mielgo, Xabier; Lundeberg, Joakim; Green, Henrik

    2012-09-10

    The growing collection of publicly available high-throughput data provides an invaluable resource for generating preliminary in silico data in support of novel hypotheses. In this study we used a cross-dataset meta-analysis strategy to identify novel candidate genes and genetic variations relevant to paclitaxel/carboplatin-induced myelosuppression and neuropathy. We identified genes affected by drug exposure and present in tissues associated with toxicity. From ten top-ranked genes 42 non-synonymous single nucleotide polymorphisms (SNPs) were identified in silico and genotyped in 94 cancer patients treated with carboplatin/paclitaxel. We observed variations in 11 SNPs, of which seven were present in a sufficient frequency for statistical evaluation. Of these seven SNPs, three were present in ABCA1 and ATM, and showed significant or borderline significant association with either myelosuppression or neuropathy. The strikingly high number of associations between genotype and clinically observed toxicity provides support for our data-driven computations strategy to identify biomarkers for drug toxicity. PMID:22759513

  9. Candidate Genes for Testicular Cancer Evaluated by In Situ Protein Expression Analyses on Tissue Microarrays

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    Rolf I. Skotheim

    2003-09-01

    Full Text Available By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.

  10. Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma

    Institute of Scientific and Technical Information of China (English)

    David Cogdell; Woonbok Chung; Yuexin Liu; Matthew McDonald; Kenneth Aldape; Jean-Pierre J. Issa; Gregory N. Fuller; Wei Zhang

    2011-01-01

    Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion.AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1.Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n = 27), and the degree of methylation correlated with Iow levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that Iow AJAP1 gene expression was associated with decreased survival. Thus,both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.

  11. Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma.

    Science.gov (United States)

    Cogdell, David; Chung, Woonbok; Liu, Yuexin; McDonald, J Matthew; Aldape, Kenneth; Issa, Jean-Pierre J; Fuller, Gregory N; Zhang, Wei

    2011-04-01

    Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.

  12. A KH Domain-Containing Putative RNA-Binding Protein Is Critical for Heat Stress-Responsive Gene Regulation and Thermotolerance in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Qingmei Guan; Changlong Wen; Haitao Zeng; Jianhua Zhu

    2013-01-01

    Heat stress is a severe environmental factor that significantly reduces plant growth and delays development.Heat stress factors (HSFs) are a class of transcription factors that are synthesized rapidly in response to elevations in temperature and are responsible for the transcription of many heat stress-responsive genes including those encoding heat shock proteins (HSPs).There are 21 HSFs in Arabidopsis,and recent studies have established that the HSFA1 family members are master regulators for the remaining HSFs.However,very little is known about upstream molecular factors that control the expression of HSFA1 genes and other HSF genes under heat stress.Through a forward genetic analysis,we identified RCF3,a K homology (KH) domain-containing nuclear-localized putative RNA-binding protein.RCF3 is a negative regulator of most HSFs,including HSFAla,HSFAlb,and HSFAld.In contrast,RCF3 positively controls the expression of HSFAle,HSFA3,HSFA9,HSFB3,and DREB2C.Consistently with the overall increased accumulation of heat-responsive genes,the rcf3 mutant plants are more tolerant than the wild-type to heat stress.Together,our results suggest that a KH domain-containing putative RNA-binding protein RCF3 is an important upstream regulator for heat stress-responsive gene expression and thermotolerance in Arabidopsis.

  13. Clinical phenotype and candidate genes for the 5q31.3 microdeletion syndrome.

    Science.gov (United States)

    Hosoki, Kana; Ohta, Tohru; Natsume, Jun; Imai, Sumiko; Okumura, Akihisa; Matsui, Takeshi; Harada, Naoki; Bacino, Carlos A; Scaglia, Fernando; Jones, Jeremy Y; Niikawa, Norio; Saitoh, Shinji

    2012-08-01

    Array-based technologies have led to the identification of many novel microdeletion and microduplication syndromes demonstrating multiple congenital anomalies and intellectual disability (MCA/ID). We have used chromosomal microarray analysis for the evaluation of patients with MCA/ID and/or neonatal hypotonia. Three overlapping de novo microdeletions at 5q31.3 with the shortest region of overlap (SRO) of 370 kb were detected in three unrelated patients. These patients showed similar clinical features including severe neonatal hypotonia, neonatal feeding difficulties, respiratory distress, characteristic facial features, and severe developmental delay. These features are consistent with the 5q31.3 microdeletion syndrome originally proposed by Shimojima et al., providing further evidence that this syndrome is clinically discernible. The 370 kb SRO encompasses only four RefSeq genes including neuregulin 2 (NRG2) and purine-rich element binding protein A (PURA). NRG2 is one of the members of the neuregulin family related to neuronal and glial cell growth and differentiation, thus making NRG2 a good candidate for the observed phenotype. Moreover, PURA is also a good candidate because Pura-deficient mice demonstrate postnatal neurological manifestations.

  14. Subgroup C avian metapneumovirus (MPV) and the recently isolated human MPV exhibit a common organization but have extensive sequence divergence in their putative SH and G genes.

    Science.gov (United States)

    Toquin, D; de Boisseson, C; Beven, V; Senne, D A; Eterradossi, N

    2003-08-01

    The genes encoding the putative small hydrophobic (SH), attachment (G) and polymerase (L) proteins of the Colorado isolate of subgroup C avian pneumovirus (APV) were entirely or partially sequenced. They all included metapneumovirus (MPV)-like gene start and gene end sequences. The deduced Colorado SH protein shared 26.9 and 21.7 % aa identity with its counterpart in human MPV (hMPV) and APV subgroup A, respectively, but its only significant aa similarities were to hMPV. Conserved features included a common hydrophobicity profile with an unique transmembrane domain and the conservation of most extracellular cysteine residues. The Colorado putative G gene encoded several ORFs, the longer of which encoded a 252 aa long type II glycoprotein with aa similarities to hMPV G only (20.6 % overall aa identity with seven conserved N-terminal residues). The putative Colorado G protein shared, at best, 21.0 % aa identity with its counterparts in the other APV subgroups and did not contain the extracellular cysteine residues and short aa stretch highly conserved in other APVs. The N-terminal end of the Colorado L protein exhibited 73.6 and 54.9 % aa identity with hMPV and APV subgroup A, respectively, with four aa blocks highly conserved among Pneumovirus: Phylogenetic analysis performed on the nt sequences confirmed that the L sequences from MPVs were genetically related, whereas analysis of the G sequences revealed that among MPVs, only APV subgroups A, B and D clustered together, independently of both the Colorado isolate and hMPV, which shared weak genetic relatedness at the G gene level.

  15. Exocrine pancreatic insufficiency in the Eurasian dog breed - inheritance and exclusion of two candidate genes

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Fredholm, Merete

    2007-01-01

    Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the SINGLES...... method for three families of the Eurasian dog breed. Our data were consistent with an autosomal recessive mode of inheritance. In addition, we performed a linkage analysis in these families using four microsatellite markers on CFA3 and two microsatellites on CFA23. Based on our results, we excluded...... the canine orthologs of the human cholecystokinin (CCK) and the cholecystokinin A receptor (CCKAR) genes as candidates for exocrine pancreatic insufficiency....

  16. A temperature-sensitive allele of a putative mRNA splicing helicase down-regulates many cell wall genes and causes radial swelling in Arabidopsis thaliana.

    Science.gov (United States)

    Howles, Paul A; Gebbie, Leigh K; Collings, David A; Varsani, Arvind; Broad, Ronan C; Ohms, Stephen; Birch, Rosemary J; Cork, Ann H; Arioli, Tony; Williamson, Richard E

    2016-05-01

    The putative RNA helicase encoded by the Arabidopsis gene At1g32490 is a homolog of the yeast splicing RNA helicases Prp2 and Prp22. We isolated a temperature-sensitive allele (rsw12) of the gene in a screen for root radial swelling mutants. Plants containing this allele grown at the restrictive temperature showed weak radial swelling, were stunted with reduced root elongation, and contained reduced levels of cellulose. The role of the protein was further explored by microarray analysis. By using both fold change cutoffs and a weighted gene coexpression network analysis (WGCNA) to investigate coexpression of genes, we found that the radial swelling phenotype was not linked to genes usually associated with primary cell wall biosynthesis. Instead, the mutation has strong effects on expression of secondary cell wall related genes. Many genes potentially associated with secondary walls were present in the most significant WGCNA module, as were genes coding for arabinogalactans and proteins with GPI anchors. The proportion of up-regulated genes that possess introns in rsw12 was above that expected if splicing was unrelated to the activity of the RNA helicase, suggesting that the helicase does indeed play a role in splicing in Arabidopsis. The phenotype may be due to a change in the expression of one or more genes coding for cell wall proteins.

  17. A temperature-sensitive allele of a putative mRNA splicing helicase down-regulates many cell wall genes and causes radial swelling in Arabidopsis thaliana.

    Science.gov (United States)

    Howles, Paul A; Gebbie, Leigh K; Collings, David A; Varsani, Arvind; Broad, Ronan C; Ohms, Stephen; Birch, Rosemary J; Cork, Ann H; Arioli, Tony; Williamson, Richard E

    2016-05-01

    The putative RNA helicase encoded by the Arabidopsis gene At1g32490 is a homolog of the yeast splicing RNA helicases Prp2 and Prp22. We isolated a temperature-sensitive allele (rsw12) of the gene in a screen for root radial swelling mutants. Plants containing this allele grown at the restrictive temperature showed weak radial swelling, were stunted with reduced root elongation, and contained reduced levels of cellulose. The role of the protein was further explored by microarray analysis. By using both fold change cutoffs and a weighted gene coexpression network analysis (WGCNA) to investigate coexpression of genes, we found that the radial swelling phenotype was not linked to genes usually associated with primary cell wall biosynthesis. Instead, the mutation has strong effects on expression of secondary cell wall related genes. Many genes potentially associated with secondary walls were present in the most significant WGCNA module, as were genes coding for arabinogalactans and proteins with GPI anchors. The proportion of up-regulated genes that possess introns in rsw12 was above that expected if splicing was unrelated to the activity of the RNA helicase, suggesting that the helicase does indeed play a role in splicing in Arabidopsis. The phenotype may be due to a change in the expression of one or more genes coding for cell wall proteins. PMID:27008640

  18. QTL analysis and candidate gene mapping for the polyphenol content in cider apple.

    Directory of Open Access Journals (Sweden)

    Cindy F Verdu

    Full Text Available Polyphenols have favorable antioxidant potential on human health suggesting that their high content is responsible for the beneficial effects of apple consumption. They control the quality of ciders as they predominantly account for astringency, bitterness, color and aroma. In this study, we identified QTLs controlling phenolic compound concentrations and the average polymerization degree of flavanols in a cider apple progeny. Thirty-two compounds belonging to five groups of phenolic compounds were identified and quantified by reversed phase liquid chromatography on both fruit extract and juice, over three years. The average polymerization degree of flavanols was estimated in fruit by phloroglucinolysis coupled to HPLC. Parental maps were built using SSR and SNP markers and used for the QTL analysis. Sixty-nine and 72 QTLs were detected on 14 and 11 linkage groups of the female and male maps, respectively. A majority of the QTLs identified in this study are specific to this population, while others are consistent with previous studies. This study presents for the first time in apple, QTLs for the mean polymerization degree of procyanidins, for which the mechanisms involved remains unknown to this day. Identification of candidate genes underlying major QTLs was then performed in silico and permitted the identification of 18 enzymes of the polyphenol pathway and six transcription factors involved in the apple anthocyanin regulation. New markers were designed from sequences of the most interesting candidate genes in order to confirm their co-localization with underlying QTLs by genetic mapping. Finally, the potential use of these QTLs in breeding programs is discussed.

  19. Molecular characterization of the leptin receptor gene as a candidate gene in the pulmonary hypertension syndrome in broiler chickens.

    Science.gov (United States)

    Bamidele, O; Van As, P; Elferink, M G

    2012-12-15

    Leptin Receptor Gene (LEPR) is a candidate gene in understanding the genetic basis of the Pulmonary Hypertension Syndrome (PHS) in broilers. Identification and evaluation of genetic polymorphisms in LEPR may provide a link between traits like Body Weight (BW) and Total Ventricle weight (TV) to the development of PHS. In this study, primers were designed in exons, upstream and downstream sequences to identify mutations in the LEPR on four broilers selected with respect to the PHS-related traits. About 77% of the 11,820 bp of the LEPR gene covered by the primers were sequenced. No mutations were found between the chickens associating the traits to the occurrence of PHS. However, 42 single nucleotide polymorphisms and four Indels were found between the reference sequences of the red jungle fowl and the experimental population. Ten of these mutations were not previously reported in LEPR at the genomic and transcript sequences (NP_989654.1, ENSGALT00000018009). The 10 mutations include six SNPs in intron regions, two Indels and two non-synonymous SNPs. The two new non-synonymous SNPs; G301A and A1637G, led to amino acid change A89T and N534S, respectively. PMID:23755410

  20. Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5.

    Science.gov (United States)

    Tanabe, Kazuyuki; Arisue, Nobuko; Palacpac, Nirianne M Q; Yagi, Masanori; Tougan, Takahiro; Honma, Hajime; Ferreira, Marcelo U; Färnert, Anna; Björkman, Anders; Kaneko, Akira; Nakamura, Masatoshi; Hirayama, Kenji; Mita, Toshihiro; Horii, Toshihiro

    2012-02-21

    SERA5 is regarded as a promising malaria vaccine candidate of the most virulent human malaria parasite Plasmodium falciparum. SERA5 is a 120 kDa abundantly expressed blood-stage protein containing a papain-like protease. Since substantial polymorphism in blood-stage vaccine candidates may potentially limit their efficacy, it is imperative to fully investigate polymorphism of the SERA5 gene (sera5). In this study, we performed evolutionary and population genetic analysis of sera5. The level of inter-species divergence (kS=0.076) between P. falciparum and Plasmodium reichenowi, a closely related chimpanzee malaria parasite is comparable to that of housekeeping protein genes. A signature of purifying selection was detected in the proenzyme and enzyme domains. Analysis of 445 near full-length P. falciparum sera5 sequences from nine countries in Africa, Southeast Asia, Oceania and South America revealed extensive variations in the number of octamer repeat (OR) and serine repeat (SR) regions as well as substantial level of single nucleotide polymorphism (SNP) in non-repeat regions (2562 bp). Remarkably, a 14 amino acid sequence of SERA5 (amino acids 59-72) that is known to be the in vitro target of parasite growth inhibitory antibodies was found to be perfectly conserved in all 445 worldwide isolates of P. falciparum evaluated. Unlike other major vaccine target antigen genes such as merozoite surface protein-1, apical membrane antigen-1 or circumsporozoite protein, no strong evidence for positive selection was detected for SNPs in the non-repeat regions of sera5. A biased geographical distribution was observed in SNPs as well as in the haplotypes of the sera5 OR and SR regions. In Africa, OR- and SR-haplotypes with low frequency (<5%) and SNPs with minor allele frequency (<5%) were abundant and were mostly continent-specific. Consistently, significant genetic differentiation, assessed by the Wright's fixation index (Fst) of inter-population variance in allele frequencies

  1. Multi-Trait GWAS and New Candidate Genes Annotation for Growth Curve Parameters in Brahman Cattle.

    Science.gov (United States)

    Crispim, Aline Camporez; Kelly, Matthew John; Guimarães, Simone Eliza Facioni; Fonseca e Silva, Fabyano; Fortes, Marina Rufino Salinas; Wenceslau, Raphael Rocha; Moore, Stephen

    2015-01-01

    Understanding the genetic architecture of beef cattle growth cannot be limited simply to the genome-wide association study (GWAS) for body weight at any specific ages, but should be extended to a more general purpose by considering the whole growth trajectory over time using a growth curve approach. For such an approach, the parameters that are used to describe growth curves were treated as phenotypes under a GWAS model. Data from 1,255 Brahman cattle that were weighed at birth, 6, 12, 15, 18, and 24 months of age were analyzed. Parameter estimates, such as mature weight (A) and maturity rate (K) from nonlinear models are utilized as substitutes for the original body weights for the GWAS analysis. We chose the best nonlinear model to describe the weight-age data, and the estimated parameters were used as phenotypes in a multi-trait GWAS. Our aims were to identify and characterize associated SNP markers to indicate SNP-derived candidate genes and annotate their function as related to growth processes in beef cattle. The Brody model presented the best goodness of fit, and the heritability values for the parameter estimates for mature weight (A) and maturity rate (K) were 0.23 and 0.32, respectively, proving that these traits can be a feasible alternative when the objective is to change the shape of growth curves within genetic improvement programs. The genetic correlation between A and K was -0.84, indicating that animals with lower mature body weights reached that weight at younger ages. One hundred and sixty seven (167) and two hundred and sixty two (262) significant SNPs were associated with A and K, respectively. The annotated genes closest to the most significant SNPs for A had direct biological functions related to muscle development (RAB28), myogenic induction (BTG1), fetal growth (IL2), and body weights (APEX2); K genes were functionally associated with body weight, body height, average daily gain (TMEM18), and skeletal muscle development (SMN1). Candidate

  2. Multi-Trait GWAS and New Candidate Genes Annotation for Growth Curve Parameters in Brahman Cattle.

    Directory of Open Access Journals (Sweden)

    Aline Camporez Crispim

    Full Text Available Understanding the genetic architecture of beef cattle growth cannot be limited simply to the genome-wide association study (GWAS for body weight at any specific ages, but should be extended to a more general purpose by considering the whole growth trajectory over time using a growth curve approach. For such an approach, the parameters that are used to describe growth curves were treated as phenotypes under a GWAS model. Data from 1,255 Brahman cattle that were weighed at birth, 6, 12, 15, 18, and 24 months of age were analyzed. Parameter estimates, such as mature weight (A and maturity rate (K from nonlinear models are utilized as substitutes for the original body weights for the GWAS analysis. We chose the best nonlinear model to describe the weight-age data, and the estimated parameters were used as phenotypes in a multi-trait GWAS. Our aims were to identify and characterize associated SNP markers to indicate SNP-derived candidate genes and annotate their function as related to growth processes in beef cattle. The Brody model presented the best goodness of fit, and the heritability values for the parameter estimates for mature weight (A and maturity rate (K were 0.23 and 0.32, respectively, proving that these traits can be a feasible alternative when the objective is to change the shape of growth curves within genetic improvement programs. The genetic correlation between A and K was -0.84, indicating that animals with lower mature body weights reached that weight at younger ages. One hundred and sixty seven (167 and two hundred and sixty two (262 significant SNPs were associated with A and K, respectively. The annotated genes closest to the most significant SNPs for A had direct biological functions related to muscle development (RAB28, myogenic induction (BTG1, fetal growth (IL2, and body weights (APEX2; K genes were functionally associated with body weight, body height, average daily gain (TMEM18, and skeletal muscle development (SMN1

  3. Identifying candidate genes affecting developmental time in Drosophila melanogaster: pervasive pleiotropy and gene-by-environment interaction

    Directory of Open Access Journals (Sweden)

    Hasson Esteban

    2008-08-01

    Full Text Available Abstract Background Understanding the genetic architecture of ecologically relevant adaptive traits requires the contribution of developmental and evolutionary biology. The time to reach the age of reproduction is a complex life history trait commonly known as developmental time. In particular, in holometabolous insects that occupy ephemeral habitats, like fruit flies, the impact of developmental time on fitness is further exaggerated. The present work is one of the first systematic studies of the genetic basis of developmental time, in which we also evaluate the impact of environmental variation on the expression of the trait. Results We analyzed 179 co-isogenic single P[GT1]-element insertion lines of Drosophila melanogaster to identify novel genes affecting developmental time in flies reared at 25°C. Sixty percent of the lines showed a heterochronic phenotype, suggesting that a large number of genes affect this trait. Mutant lines for the genes Merlin and Karl showed the most extreme phenotypes exhibiting a developmental time reduction and increase, respectively, of over 2 days and 4 days relative to the control (a co-isogenic P-element insertion free line. In addition, a subset of 42 lines selected at random from the initial set of 179 lines was screened at 17°C. Interestingly, the gene-by-environment interaction accounted for 52% of total phenotypic variance. Plastic reaction norms were found for a large number of developmental time candidate genes. Conclusion We identified components of several integrated time-dependent pathways affecting egg-to-adult developmental time in Drosophila. At the same time, we also show that many heterochronic phenotypes may arise from changes in genes involved in several developmental mechanisms that do not explicitly control the timing of specific events. We also demonstrate that many developmental time genes have pleiotropic effects on several adult traits and that the action of most of them is sensitive

  4. A shell regeneration assay to identify biomineralization candidate genes in mytilid mussels.

    Science.gov (United States)

    Hüning, Anne K; Lange, Skadi M; Ramesh, Kirti; Jacob, Dorrit E; Jackson, Daniel J; Panknin, Ulrike; Gutowska, Magdalena A; Philipp, Eva E R; Rosenstiel, Philip; Lucassen, Magnus; Melzner, Frank

    2016-06-01

    Biomineralization processes in bivalve molluscs are still poorly understood. Here we provide an analysis of specifically expressed sequences from a mantle transcriptome of the blue mussel, Mytilus edulis. We then developed a novel, integrative shell injury assay to test, whether biomineralization candidate genes highly expressed in marginal and pallial mantle could be induced in central mantle tissue underlying the damaged shell areas. This experimental approach makes it possible to identify gene products that control the chemical micro-environment during calcification as well as organic matrix components. This is unlike existing methodological approaches that work retroactively to characterize calcification relevant molecules and are just able to examine organic matrix components that are present in completed shells. In our assay an orthogonal array of nine 1mm holes was drilled into the left valve, and mussels were suspended in net cages for 20, 29 and 36days to regenerate. Structural observations using stereo-microscopy, SEM and Raman spectroscopy revealed organic sheet synthesis (day 20) as the first step of shell-repair followed by the deposition of calcite crystals (days 20 and 29) and aragonite tablets (day 36). The regeneration period was characterized by time-dependent shifts in gene expression in left central mantle tissue underlying the injured shell, (i) increased expression of two tyrosinase isoforms (TYR3: 29-fold and TYR6: 5-fold) at day 20 with a decline thereafter, (ii) an increase in expression of a gene encoding a nacrein-like protein (max. 100-fold) on day 29. The expression of an acidic Asp-Ser-rich protein was enhanced during the entire regeneration process. This proof-of-principle study demonstrates that genes that are specifically expressed in pallial and marginal mantle tissue can be induced (4 out of 10 genes) in central mantle following experimental injury of the overlying shell. Our findings suggest that regeneration assays can be used

  5. Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth

    Directory of Open Access Journals (Sweden)

    Tisdale Michele

    2009-09-01

    Full Text Available Abstract Background Like humans, the living elephants are unusual among mammals in being sparsely covered with hair. Relative to extant elephants, the extinct woolly mammoth, Mammuthus primigenius, had a dense hair cover and extremely long hair, which likely were adaptations to its subarctic habitat. The fibroblast growth factor 5 (FGF5 gene affects hair length in a diverse set of mammalian species. Mutations in FGF5 lead to recessive long hair phenotypes in mice, dogs, and cats; and the gene has been implicated in hair length variation in rabbits. Thus, FGF5 represents a leading candidate gene for the phenotypic differences in hair length notable between extant elephants and the woolly mammoth. We therefore sequenced the three exons (except for the 3' UTR and a portion of the promoter of FGF5 from the living elephantid species (Asian, African savanna and African forest elephants and, using protocols for ancient DNA, from a woolly mammoth. Results Between the extant elephants and the mammoth, two single base substitutions were observed in FGF5, neither of which alters the amino acid sequence. Modeling of the protein structure suggests that the elephantid proteins fold similarly to the human FGF5 protein. Bioinformatics analyses and DNA sequencing of another locus that has been implicated in hair cover in humans, type I hair keratin pseudogene (KRTHAP1, also yielded negative results. Interestingly, KRTHAP1 is a pseudogene in elephantids as in humans (although fully functional in non-human primates. Conclusion The data suggest that the coding sequence of the FGF5 gene is not the critical determinant of hair length differences among elephantids. The results are discussed in the context of hairlessness among mammals and in terms of the potential impact of large body size, subarctic conditions, and an aquatic ancestor on hair cover in the Proboscidea.

  6. Candidate genes that may be responsible for the unusual resistances exhibited by Bacillus pumilus SAFR-032 spores.

    Directory of Open Access Journals (Sweden)

    Madhan R Tirumalai

    Full Text Available The spores of several Bacillus species, including Bacillus pumilus SAFR-032 and B. safensis FO-36b, which were isolated from the spacecraft assembly facility at NASA's Jet Propulsion Laboratory, are unusually resistant to UV radiation and hydrogen peroxide. In order to identify candidate genes that might be associated with these resistances, the whole genome of B. pumilus SAFR-032, and the draft genome of B. safensis FO-36b were compared in detail with the very closely related type strain B. pumilus ATCC7061(T. 170 genes are considered characteristic of SAFR-032, because they are absent from both FO-36b and ATCC7061(T. Forty of these SAFR-032 characteristic genes are entirely unique open reading frames. In addition, four genes are unique to the genomes of the resistant SAFR-032 and FO-36b. Fifty three genes involved in spore coat formation, regulation and germination, DNA repair, and peroxide resistance, are missing from all three genomes. The vast majority of these are cleanly deleted from their usual genomic context without any obvious replacement. Several DNA repair and peroxide resistance genes earlier reported to be unique to SAFR-032 are in fact shared with ATCC7061(T and no longer considered to be promising candidates for association with the elevated resistances. Instead, several SAFR-032 characteristic genes were identified, which along with one or more of the unique SAFR-032 genes may be responsible for the elevated resistances. These new candidates include five genes associated with DNA repair, namely, BPUM_0608 a helicase, BPUM_0652 an ATP binding protein, BPUM_0653 an endonuclease, BPUM_0656 a DNA cytosine-5- methyltransferase, and BPUM_3674 a DNA helicase. Three of these candidate genes are in immediate proximity of two conserved hypothetical proteins, BPUM_0654 and BPUM_0655 that are also absent from both FO-36b and ATCC7061(T. This cluster of five genes is considered to be an especially promising target for future experimental

  7. Genomic structure of the rat major AP endonuclease gene (Apex with an adjacent putative O-sialoglycoprotease gene (Prsmg1/Gcpl1 and a processed Apex pseudogene (Apexp1.

    Directory of Open Access Journals (Sweden)

    Yao,Ming

    1999-12-01

    Full Text Available Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active Apex gene and a processed pseudogene were isolated from a rat genomic library. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1 gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization. The processed pseudogene (designated as rat Apexp1 has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, although several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LINE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp1 arose 23 million years ago and that the non-functionalization occurred 15 million years ago.

  8. Association study of candidate genes for susceptibility to schizophrenia and bipolar disorder on chromosome 22Q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob; Binderup, Helle; Mors, Ole;

    Chromosome 22q is suspected to harbor risk genes for schizophrenia as well as bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. In a recent study of distantly related patients from...... the Faroe Islands we have obtained evidence suggesting two regions on chromosome 22q13 to potentially harbor susceptibility genes for both schizophrenia and bipolar affective disorder. We have selected a number of candidate genes from these two regions for further analysis, including the neuro-gene WKL1...... and unrelated controls, and in a Scottish case-control sample comprising 200 schizophrenics, 200 bipolar patients and 200 controls. None of the investigated SNPs have so far showed strong evidence of association to either bipolar disorder or schizophrenia....

  9. Comprehensive analysis of SET domain gene family in foxtail millet identifies the putative role of SiSET14 in abiotic stress tolerance

    Science.gov (United States)

    Yadav, Chandra Bhan; Muthamilarasan, Mehanathan; Dangi, Anand; Shweta, Shweta; Prasad, Manoj

    2016-01-01

    SET domain-containing genes catalyse histone lysine methylation, which alters chromatin structure and regulates the transcription of genes that are involved in various developmental and physiological processes. The present study identified 53 SET domain-containing genes in C4 panicoid model, foxtail millet (Setaria italica) and the genes were physically mapped onto nine chromosomes. Phylogenetic and structural analyses classified SiSET proteins into five classes (I–V). RNA-seq derived expression profiling showed that SiSET genes were differentially expressed in four tissues namely, leaf, root, stem and spica. Expression analyses using qRT-PCR was performed for 21 SiSET genes under different abiotic stress and hormonal treatments, which showed differential expression of these genes during late phase of stress and hormonal treatments. Significant upregulation of SiSET gene was observed during cold stress, which has been confirmed by over-expressing a candidate gene, SiSET14 in yeast. Interestingly, hypermethylation was observed in gene body of highly differentially expressed genes, whereas methylation event was completely absent in their transcription start sites. This suggested the occurrence of demethylation events during various abiotic stresses, which enhance the gene expression. Altogether, the present study would serve as a base for further functional characterization of SiSET genes towards understanding their molecular roles in conferring stress tolerance. PMID:27585852

  10. Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.

    Science.gov (United States)

    Wei, F J; Cai, C Y; Yu, P; Lv, J; Ling, C; Shi, W T; Jiao, H X; Chang, B C; Yang, F H; Tian, Y; Li, M S; Wang, Y H; Zou, L; Shi, J M; Chen, L M; Li, W D

    2015-01-01

    Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation. PMID:26634513

  11. Differential expression patterns in chemosensory and non-chemosensory tissues of putative chemosensory genes identified by transcriptome analysis of insect pest the purple stem borer Sesamia inferens (Walker.

    Directory of Open Access Journals (Sweden)

    Ya-Nan Zhang

    Full Text Available BACKGROUND: A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. METHODOLOGY/PRINCIPAL FINDINGS: We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, among them 87 are novel in this species, including 24 transcripts encoding for odorant binding proteins (OBPs, 24 for chemosensory proteins (CSPs, 2 for sensory neuron membrane proteins (SNMPs, 39 for odorant receptors (ORs and 3 for ionotropic receptors (IRs. The transcriptome analyses were validated and quantified with a detailed global expression profiling by Reverse Transcription-PCR for all 92 transcripts and by Quantitative Real Time RT-PCR for selected 16 ones. Among the chemosensory gene subfamilies, CSP transcripts are most widely and evenly expressed in different tissues and stages, OBP transcripts showed a clear antenna bias and most of OR transcripts are only detected in adult antennae. Our results also revealed that some OR transcripts, such as the transcripts of SNMP2 and 2 IRs were expressed in non-chemosensory tissues, and some CSP transcripts were antenna-biased expression. Furthermore, no chemosensory transcript is specific to female sex pheromone gland and very few are found in the heads. CONCLUSION: Our study revealed that there are a large number of chemosensory genes expressed in S. inferens, and some of them displayed unusual expression profile in non-chemosensory tissues. The identification of a large set of putative chemosensory genes of each subfamily from a single insect species, together with their different expression profiles provide further information in understanding the functions of these chemosensory genes in S. inferens as

  12. De novo characterization of the Chinese fir (Cunninghamia lanceolata transcriptome and analysis of candidate genes involved in cellulose and lignin biosynthesis

    Directory of Open Access Journals (Sweden)

    Huang Hua-Hong

    2012-11-01

    were analyzed by qRT-PCR to explore their putative functions. Conclusions A substantial fraction of transcript sequences was obtained from the deep sequencing of Chinese fir. The assembled Unigene dataset was used to discover candidate genes of cellulose and lignin biosynthesis. This transcriptome dataset will provide a comprehensive sequence resource for molecular genetics research of C. lanceolata.

  13. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

    Science.gov (United States)

    Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

    2015-06-01

    Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity.

  14. Isolation of candidate genes and physical mapping in the Familial Dysautonomia region of chromosome 9q31

    Energy Technology Data Exchange (ETDEWEB)

    Slaugenhaupt, S.A.; Liebert, C.B.; Monahan, M. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    Familial Dysautonomia is an autosomal recessive disorder characterized by the developmental loss of both sensory and autonomic neurons. We have mapped the DYS gene to human chromosome 9q31-33 by genetic linkage analysis of 26 Ashkenazi Jewish pedigrees. The gene is located in a 3 cM interval between D9S310 and D9S105. We have examined several new SSCP and repeat polymorphisms and have successfully narrowed the minimum candidate region to approximately 300 kb using linkage disequilibrium. A YAC contig that spans 1.5 Mb has been constructed using both Alu-PCR and STS screening methods. In addition, the YACs were used to isolate cosmids by direct hybridization to the Lawrence Livermore National Laboratory chromosome 9 flow-sorted cosmid library. Having cloned the minimal candidate region, we are now constructing a detailed transcription map of the DYS region of chromosome 9. Using exon amplification, we have rapidly identified exon sequences and have used these as probes to isolate three candidate genes. These genes are currently being sequenced and will be assessed for mutations using both SSCP analysis and direct sequencing. A detailed physical map of the DYS region, as well as sequence and homology information for DYS candidate genes, will be presented.

  15. Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia

    Institute of Scientific and Technical Information of China (English)

    LiYu; ChunhuiLiu; JeffVandeusen; BrianBecknell; ZunyanDai; Yue-ZhongWu; AparnaRaval; Te-HuiLiu; WeiDing; CharleneMao; ShujunLiu; LauraTSmith; StephenLee; LauraRassenti; GuidoMarcucci; JohnByrd; MichaelACaligiuri; ChristophPlass

    2005-01-01

    DNA methylation is associated with malignant transformation, but limitations imposed by genetic variability, tumor heterogeneity, availability of paired normal tissues and methodologies for global assessment of DNA methylation have limited progress in understanding the extent of epigenetic events in the initiation and progression of human cancer and in identifying genes that undergo methylation during cancer. We developed a mouse model of T/natural killer acute lymphoblastic leukemia that is always preceded by polyclonal lymphocyte expansion to determine how aberrant promoter DNA methylation and consequent gene silencing might be contributing to leukemic transformation. We used restriction landmark genomic scanning with this mouse model of preleukemia reproducibly progressing to leukemia to show that specific genomic methylation is associated with only the leukemic phase and is not random. We also identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of other human cancers.

  16. Genetic study of autosomal dominant progressive external ophthalmoplegia and familial myasthenia gravis : linkage analysis, candidate gene cloning and mutation detection

    OpenAIRE

    Li, Fang-Yuan

    2001-01-01

    Identification of genes responsible for familial human diseases is a major task of medical genetics. In this process, linkage analysis, candidate gene screening and mutation detection are the three major steps (Paper I-VI). The purpose of this study was to elucidate the genetic backgrounds of autosomal dominant progressive external ophthalmoplegia (adPEO) and familial inyasthenia gravis (FMG). The methods applied in this study for linkage analysis and repeat expansion we...

  17. Linkage study of 14 candidate genes and loci in four large Dutch families with vesico-ureteral reflux

    NARCIS (Netherlands)

    Eerde, A.M. van; Koeleman, B.P.C.; Kamp, J.M. van de; Jong, T.P.V.M. de; Wijmenga, C.; Giltay, J.C.

    2007-01-01

    Vesico-ureteral reflux (VUR) is a major contributing factor to end-stage renal disease in paediatric patients. Primary VUR is a familial disorder, but little is known about its genetic causes. To investigate the involvement of 12 functional candidate genes and two reported loci in VUR, we performed

  18. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    Science.gov (United States)

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  19. Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test.

    Science.gov (United States)

    Young, E E; Bryant, C D; Lee, S E; Peng, X; Cook, B; Nair, H K; Dreher, K J; Zhang, X; Palmer, A A; Chung, J M; Mogil, J S; Chesler, E J; Lariviere, W R

    2016-07-01

    Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation. PMID:27231153

  20. A Parthenogenesis Gene Candidate and Evidence for Segmental Allopolyploidy in Apomictic Brachiaria decumbens.

    Science.gov (United States)

    Worthington, Margaret; Heffelfinger, Christopher; Bernal, Diana; Quintero, Constanza; Zapata, Yeny Patricia; Perez, Juan Guillermo; De Vega, Jose; Miles, John; Dellaporta, Stephen; Tohme, Joe

    2016-07-01

    Apomixis, asexual reproduction through seed, enables breeders to identify and faithfully propagate superior heterozygous genotypes by seed without the disadvantages of vegetative propagation or the expense and complexity of hybrid seed production. The availability of new tools such as genotyping by sequencing and bioinformatics pipelines for species lacking reference genomes now makes the construction of dense maps possible in apomictic species, despite complications including polyploidy, multisomic inheritance, self-incompatibility, and high levels of heterozygosity. In this study, we developed saturated linkage maps for the maternal and paternal genomes of an interspecific Brachiaria ruziziensis (R. Germ. and C. M. Evrard) × B. decumbens Stapf. F1 mapping population in order to identify markers linked to apomixis. High-resolution molecular karyotyping and comparative genomics with Setaria italica (L.) P. Beauv provided conclusive evidence for segmental allopolyploidy in B. decumbens, with strong preferential pairing of homologs across the genome and multisomic segregation relatively more common in chromosome 8. The apospory-specific genomic region (ASGR) was mapped to a region of reduced recombination on B. decumbens chromosome 5. The Pennisetum squamulatum (L.) R.Br. PsASGR-BABY BOOM-like (psASGR-BBML)-specific primer pair p779/p780 was in perfect linkage with the ASGR in the F1 mapping population and diagnostic for reproductive mode in a diversity panel of known sexual and apomict Brachiaria (Trin.) Griseb. and P. maximum Jacq. germplasm accessions and cultivars. These findings indicate that ASGR-BBML gene sequences are highly conserved across the Paniceae and add further support for the postulation of the ASGR-BBML as candidate genes for the apomictic function of parthenogenesis. PMID:27206716

  1. A Parthenogenesis Gene Candidate and Evidence for Segmental Allopolyploidy in Apomictic Brachiaria decumbens.

    Science.gov (United States)

    Worthington, Margaret; Heffelfinger, Christopher; Bernal, Diana; Quintero, Constanza; Zapata, Yeny Patricia; Perez, Juan Guillermo; De Vega, Jose; Miles, John; Dellaporta, Stephen; Tohme, Joe

    2016-07-01

    Apomixis, asexual reproduction through seed, enables breeders to identify and faithfully propagate superior heterozygous genotypes by seed without the disadvantages of vegetative propagation or the expense and complexity of hybrid seed production. The availability of new tools such as genotyping by sequencing and bioinformatics pipelines for species lacking reference genomes now makes the construction of dense maps possible in apomictic species, despite complications including polyploidy, multisomic inheritance, self-incompatibility, and high levels of heterozygosity. In this study, we developed saturated linkage maps for the maternal and paternal genomes of an interspecific Brachiaria ruziziensis (R. Germ. and C. M. Evrard) × B. decumbens Stapf. F1 mapping population in order to identify markers linked to apomixis. High-resolution molecular karyotyping and comparative genomics with Setaria italica (L.) P. Beauv provided conclusive evidence for segmental allopolyploidy in B. decumbens, with strong preferential pairing of homologs across the genome and multisomic segregation relatively more common in chromosome 8. The apospory-specific genomic region (ASGR) was mapped to a region of reduced recombination on B. decumbens chromosome 5. The Pennisetum squamulatum (L.) R.Br. PsASGR-BABY BOOM-like (psASGR-BBML)-specific primer pair p779/p780 was in perfect linkage with the ASGR in the F1 mapping population and diagnostic for reproductive mode in a diversity panel of known sexual and apomict Brachiaria (Trin.) Griseb. and P. maximum Jacq. germplasm accessions and cultivars. These findings indicate that ASGR-BBML gene sequences are highly conserved across the Paniceae and add further support for the postulation of the ASGR-BBML as candidate genes for the apomictic function of parthenogenesis.

  2. QTL and candidate gene mapping for polyphenolic composition in apple fruit

    Directory of Open Access Journals (Sweden)

    Chagné David

    2012-01-01

    Full Text Available Abstract Background The polyphenolic products of the phenylpropanoid pathway, including proanthocyanidins, anthocyanins and flavonols, possess antioxidant properties that may provide health benefits. To investigate the genetic architecture of control of their biosynthesis in apple fruit, various polyphenolic compounds were quantified in progeny from a 'Royal Gala' × 'Braeburn' apple population segregating for antioxidant content, using ultra high performance liquid chromatography of extracts derived from fruit cortex and skin. Results Construction of genetic maps for 'Royal Gala' and 'Braeburn' enabled detection of 79 quantitative trait loci (QTL for content of 17 fruit polyphenolic compounds. Seven QTL clusters were stable across two years of harvest and included QTLs for content of flavanols, flavonols, anthocyanins and hydroxycinnamic acids. Alignment of the parental genetic maps with the apple whole genome sequence in silico enabled screening for co-segregation with the QTLs of a range of candidate genes coding for enzymes in the polyphenolic biosynthetic pathway. This co-location was confirmed by genetic mapping of markers derived from the gene sequences. Leucoanthocyanidin reductase (LAR1 co-located with a QTL cluster for the fruit flavanols catechin, epicatechin, procyanidin dimer and five unknown procyanidin oligomers identified near the top of linkage group (LG 16, while hydroxy cinnamate/quinate transferase (HCT/HQT co-located with a QTL for chlorogenic acid concentration mapping near the bottom of LG 17. Conclusion We conclude that LAR1 and HCT/HQT are likely to influence the concentration of these compounds in apple fruit and provide useful allele-specific markers for marker assisted selection of trees bearing fruit with healthy attributes.

  3. A multi-resource data integration approach: Identification of candidate genes regulating cell proliferation during neocortical development

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    Cynthia M Vied

    2014-08-01

    Full Text Available Neurons of the mammalian neocortex are produced by proliferating cells located in the ventricular zone (VZ lining the lateral ventricles. This is a complex and sequential process, requiring precise control of cell cycle progression, fate commitment and differentiation. We have analyzed publicly available databases from mouse and human to identify candidate genes that are potentially involved in regulating early neocortical development and neurogenesis. We used a mouse in situ hybridization dataset (The Allen Institute for Brain Science to identify 13 genes (Cdon, Celsr1, Dbi, E2f5, Eomes, Hmgn2, Neurog2, Notch1, Pcnt, Sox3, Ssrp1, Tead2, Tgif2 with high correlation of expression in the proliferating cells of the VZ of the neocortex at early stages of development (E15.5. We generated a similar human brain network using microarray and RNA-seq data (BrainSpan Atlas and identified 407 genes with high expression in the developing human VZ and subventricular zone (SVZ at 8-9 post-conception weeks. Seven of the human genes were also present in the mouse VZ network. The human and mouse networks were extended using available genetic and proteomic datasets through GeneMANIA. A gene ontology search of the mouse and human networks indicated that many of the genes are involved in the cell cycle, DNA replication, mitosis and transcriptional regulation. The reported involvement of Cdon, Celsr1, Dbi, Eomes, Neurog2, Notch1, Pcnt, Sox3, Tead2 and Tgif2 in neural development or diseases resulting from the disruption of neurogenesis validates these candidate genes. Taken together, our knowledge-based discovery method has validated the involvement of many genes already known to be involved in neocortical development and extended the potential number of genes by 100's, many of which are involved in functions related to cell proliferation but others of which are potential candidates for involvement in the regulation of neocortical development.

  4. Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children

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    Tavassoli Teresa

    2012-07-01

    Full Text Available Abstract Background Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure for association with 43 SNPs in GABRB3. Findings Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241 were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P Conclusions This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.

  5. Candidate gene association mapping for winter survival and spring regrowth in perennial ryegrass.

    Science.gov (United States)

    Yu, Xiaoqing; Pijut, Paula M; Byrne, Stephen; Asp, Torben; Bai, Guihua; Jiang, Yiwei

    2015-06-01

    Perennial ryegrass (Lolium perenne L.) is a widely cultivated cool-season grass species because of its high quality for forage and turf. Susceptibility to freezing damage limits its further use in temperate zones. The objective of this study was to identify candidate genes significantly associated with winter survival and spring regrowth in a global collection of 192 perennial ryegrass accessions. Significant differences in winter survival (WS), percentage of canopy green cover (CGC), chlorophyll index (Chl), and normalized difference vegetation index (NDVI) were found among accessions. After controlling population structure, LpLEA3 encoding a late embryogenesis abundant group 3 protein and LpCAT encoding a catalase were associated with CGC and Chl, while LpMnSOD encoding a magnesium superoxide dismutase and LpChl Cu-ZnSOD encoding a chlorophyll copper-zinc superoxide dismutase were associated with NDVI or Chl. Significant association was also discovered between C-repeat binding factor LpCBF1b and WS. Three sequence variations identified in LpCAT, LpMnSOD, and LpChl Cu-ZnSOD were synonymous substitutions, whereas one pair of adjacent single nucleotide polymorphisms (SNPs) in LpLEA3 and one SNP in LpCBF1b resulted in amino acid change. The results demonstrated that allelic variation in LpLEA3 and LpCBF1b was closely related to winter survival and spring regrowth in perennial ryegrass. PMID:25900564

  6. Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis.

    Science.gov (United States)

    Munir, Saeeda; ber Rahman, Simeen; Rehman, Sadia; Saba, Nusrat; Ahmad, Wasim; Nilsson, Staffan; Mazhar, Kehkashan; Naluai, Åsa Torinsson

    2015-03-01

    Psoriasis is a common inflammatory and hyper proliferative condition of the skin and a serious chronic systemic autoimmune disease. We undertook an association study to investigate the genetic etiology of psoriasis in a Pakistani population by genotyping single-nucleotide polymorphisms (SNPs) previously reported to be associated in genome-wide association (GWAS) or in candidate gene studies of psoriasis. Fifty seven single-nucleotide polymorphisms (SNPs) from 42 loci were genotyped in 533 psoriasis patients and 373 controls. Our results showed genome wide significant association of the MHC region (rs1265181 being the most significant from five SNPs used with overall OR=3.38; p=2.97E-18), as well as nominally significant associations at ten other loci (pfactors and molecular mechanisms behind disease in Pakistani psoriasis patients as in other populations. In addition, we show that the MHC and TNIP1 regions are significantly different in patients with psoriasis onset before the age of 40 (type I) compared to after 40 years of age (type II). MHC being associated mainly with type I while TNIP1 with type II patients.

  7. Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma

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    Badreddin Edris

    2012-01-01

    Full Text Available Leiomyosarcoma (LMS is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin and the other of which had a strongly positive enrichment score (MG-132. Given MG-132’s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS.

  8. Comparative transcriptome analysis of fruiting body and sporulating mycelia of Villosiclava virens reveals genes with putative functions in sexual reproduction.

    Science.gov (United States)

    Yu, Jun-Jie; Yu, Mi-Na; Nie, Ya-Feng; Sun, Wen-Xian; Yin, Xiao-Le; Zhao, Jie; Wang, Ya-Hui; Ding, Hui; Qi, Zhong-Qiang; Du, Yan; Huang, Li; Liu, Yong-Feng

    2016-08-01

    Sexual reproduction of heterothallic clavicipitaceous fungus Villosiclava virens (anamorph: Ustilaginoidea virens) generates ascospores, which is considered as primary infection source of rice false smut disease. However, little is known about the molecular underpinnings of sexual reproduction in V. virens. In this study, transcriptomes of V. virens in fruiting body (FB) and sporulating mycelia (SM) were compared using Illumina paired-end sequencing technology. A total of 33,384,588 and 23,765,275 clean reads of FB and SM transcriptome profiles could be used to map cDNA of V. virens, respectively. We evaluated the gene expression variations between FB and SM, a total of 488 genes therein were significantly higher expressed in FB than SM, and 342 genes were significantly higher expressed genes in SM than FB. These differentially expressed genes were annotated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Several genes were found to specifically function in sexual reproduction, involving in mating type, pheromone synthesis, signaling transduction, transcription factors, and meiosis; additionally, a few of genes were presumed to function in conidia sporulation and infection. Comparative transcriptome analysis of V. virens during FB and SM provided an overview of gene expression profiles at the transcriptional level and provided hints to better understand the molecular mechanisms of sexual development. Additionally, the data presented here also proved benefit for mining of essential genes contributing to sexual conidiation and infection. PMID:26905382

  9. Genetic effects of polymorphisms in candidate genes and the QTL region on chicken age at first egg

    Directory of Open Access Journals (Sweden)

    Zhou Min

    2011-04-01

    Full Text Available Abstract Background The age at first egg (AFE, an important indicator for sexual maturation in female chickens, is controlled by polygenes. Based on our knowledge of reproductive physiology, 6 genes including gonadotrophin releasing hormone-I (GnRH-I, neuropeptide Y (NPY, dopamine D2 receptor (DRD2, vasoactive intestinal polypeptide (VIP, VIP receptor-1 (VIPR-1, and prolactin (PRL, were selected as candidates for influencing AFE. Additionally, the region between ADL0201 and MCW0241 of chromosome Z was chosen as the candidate QTL region according to some QTL databases. The objective of the present study was to investigate the effects of mutations in candidate genes and the QTL region on chicken AFE. Results Marker-trait association analysis of 8 mutations in those 6 genes in a Chinese native population found a highly significant association (P G840327C of the GnRH-I gene with AFE, and it remained significant even with Bonferroni correction. Based on the results of the 2-tailed χ2 test, mutations T32742394C, T32742468C, G32742603A, and C33379782T in the candidate QTL region of chromosome Z were selected for marker-trait association analysis. The haplotypes of T32742394C and T32742468C were significantly associated (P T32742394C and T32742468C were located in the intron region of the SH3-domain GRB2-like 2 (SH3GL2 gene, which appeared to be associated in the endocytosis and development of the oocyte. Conclusion This study found that G840327C of the GnRH-I gene and the haplotypes of T32742394C-T32742468C of the SH3GL2 gene were associated with the chicken AFE.

  10. Whole-transcriptome survey of the putative ATP-binding cassette (ABC transporter family genes in the latex-producing laticifers of Hevea brasiliensis.

    Directory of Open Access Journals (Sweden)

    Nie Zhiyi

    Full Text Available The ATP-binding cassette (ABC proteins or transporters constitute a large protein family in plants and are involved in many different cellular functions and processes, including solute transportation, channel regulation and molecular switches, etc. Through transcriptome sequencing, a transcriptome-wide survey and expression analysis of the ABC protein genes were carried out using the laticiferous latex from Hevea brasiliensis (rubber tree. A total of 46 putative ABC family proteins were identified in the H. brasiliensis latex. These consisted of 12 'full-size', 21 'half-size' and 13 other putative ABC proteins, and all of them showed strong conservation with their Arabidopsis thaliana counterparts. This study indicated that all eight plant ABC protein paralog subfamilies were identified in the H. brasiliensis latex, of which ABCB, ABCG and ABCI were the most abundant. Real-time quantitative reverse transcription-polymerase chain reaction assays demonstrated that gene expression of several latex ABC proteins was regulated by ethylene, jasmonic acid or bark tapping (a wound stress stimulation, and that HbABCB15, HbABCB19, HbABCD1 and HbABCG21 responded most significantly of all to the abiotic stresses. The identification and expression analysis of the latex ABC family proteins could facilitate further investigation into their physiological involvement in latex metabolism and rubber biosynthesis by H. brasiliensis.

  11. Candidate gene polymorphisms among North Indians and their association with schizophrenia in a case–control study

    Indian Academy of Sciences (India)

    Prachi Semwal; Suman Prasad; Panchami G. Varma; A. M. Bhagwat; S. N. Deshpande; B. K. Thelma

    2002-08-01

    Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene–disease association studies, particularly for some complex traits. A number of candidate genes, a majority of them from the monoaminergic pathway in the brain, have been very popular in association studies with schizophrenia, a neuropsychiatric disorder. In this study diallelic/multiallelic polymorphisms in some dopaminergic, serotonergic and membrane-phospholipid-related genes have been evaluated in a control population recruited from North India. Association, if any, of these allelic variants with schizopherenia has been tested using a case–control approach. The case data have been taken from our published family-based association studies in schizophrenia. Of the eight genes tested in this study, association with schizophrenia was observed for only two gene polymorphisms, one in the promoter region of the serotonin 2A receptor gene and the other in the tryptophan hydroxylase gene. One new allele for the dopamine transporter gene (with eight repeats, 570-bp size), not reported in any population so far, has been identified in one individual in our sample. The data generated in this study, besides providing a normative background for various disease association studies, are a significant contribution to the population-specific genome database, a currently growing requirement.

  12. Candidate Gene Expression in Bos indicus Ovarian Tissues: Prepubertal and Postpubertal Heifers in Diestrus

    Science.gov (United States)

    Weller, Mayara Morena Del Cambre Amaral; Fortes, Marina Rufino S.; Porto-Neto, Laercio R.; Kelly, Matthew; Venus, Bronwyn; Kidd, Lisa; do Rego, João Paulo Arcelino; Edwards, Sophia; Boe-Hansen, Gry B.; Piper, Emily; Lehnert, Sigrid A.; Guimarães, Simone Eliza Facioni; Moore, Stephen Stewart

    2016-01-01

    Growth factors such as bone morphogenetic proteins 6, 7, 15, and two isoforms of transforming growth factor-beta (BMP6, BMP7, BMP15, TGFB1, and TGFB2), and insulin-like growth factor system act as local regulators of ovarian follicular development. To elucidate if these factors as well as others candidate genes, such as estrogen receptor 1 (ESR1), growth differentiation factor 9 (GDF9), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), bone morphogenetic protein receptor, type 2 (BMPR2), type 1 insulin-like growth factor receptor (IGFR1), and key steroidogenic enzymes cytochrome P450 aromatase and 3-β-hydroxysteroid dehydrogenase (CYP19A1 and HSD3B1) could modulate or influence diestrus on the onset of puberty in Brahman heifers, their ovarian mRNA expression was measured before and after puberty (luteal phase). Six postpubertal (POST) heifers were euthanized on the luteal phase of their second cycle, confirmed by corpus luteum observation, and six prepubertal (PRE) heifers were euthanized in the same day. Quantitative real-time PCR analysis showed that the expression of FSHR, BMP7, CYP19A1, IGF1, and IGFR1 mRNA was greater in PRE heifers, when contrasted to POST heifers. The expression of LHR and HSD3B1 was lower in PRE heifers. Differential expression of ovarian genes could be associated with changes in follicular dynamics and different cell populations that have emerged as consequence of puberty and the luteal phase. The emerging hypothesis is that BMP7 and IGF1 are co-expressed and may modulate the expression of FSHR, LHR and IGFR1, and CYP19A1. BMP7 could influence the downregulation of LHR and upregulation of FSHR and CYP19A1, which mediates the follicular dynamics in heifer ovaries. Upregulation of IGF1 expression prepuberty, compared to postpuberty diestrus, correlates with increased levels FSHR and CYP19A1. Thus, BMP7 and IGF1 may play synergic roles and were predicted to interact, from the expression data (P = 0.07, r

  13. GAD2 on chromosome 10p12 is a candidate gene for human obesity.

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    Philippe Boutin

    2003-12-01

    Full Text Available The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65 is a positional candidate gene for obesity on Chromosome 10p11-12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of gamma-aminobutyric acid (GABA, which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681-0.972], p = 0.0049 and an at-risk SNP (-243 A>G for morbid obesity (OR = 1.3, 95% CI [1.053-1.585], p = 0.014. Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (chi(2 = 7.637, p = 0.02. In the murine insulinoma cell line betaTC3, the G at-risk allele of SNP -243 A>G increased six times GAD2 promoter activity (p G SNP was associated with higher hunger scores (p = 0.007 and disinhibition scores (p = 0.028, as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic beta cells, we analyzed GAD65 antibody level as a marker of beta-cell activity and of insulin secretion. In the control group, -243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively. SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of beta-cell function (p = 0.009 and 0.01, respectively. These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.

  14. Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene.

    Science.gov (United States)

    Villela, Darine; Kimura, Lilian; Schlesinger, David; Gonçalves, Amanda; Pearson, Peter L; Suemoto, Claudia K; Pasqualucci, Carlos; Krepischi, Ana Cristina; Grinberg, Lea T; Rosenberg, Carla

    2013-12-01

    Argyrophilic grain disease (AGD) is a progressive neurodegenerative disease of the human brain that has never been associated to a particular gene locus. In the present study, we report the results of a CNV investigation in 29 individuals whose anatomopathologic investigation of the brain showed AGD. Rare CNVs were identified in six patients (21%), in particular a 40 kb deletion at 17p13.2 encompassing the CTNS gene. Homozygote mutations in CTNS are known to cause cystinosis, a disorder characterized by the intralysosomal accumulation of cystine in all tissues. We present the first CNV results in individuals presenting AGD and a possible candidate gene implicated in the disorder. PMID:24385851

  15. Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene

    Directory of Open Access Journals (Sweden)

    Darine Villela

    2013-01-01

    Full Text Available Argyrophilic grain disease (AGD is a progressive neurodegenerative disease of the human brain that has never been associated to a particular gene locus. In the present study, we report the results of a CNV investigation in 29 individuals whose anatomopathologic investigation of the brain showed AGD. Rare CNVs were identified in six patients (21%, in particular a 40 kb deletion at 17p13.2 encompassing the CTNS gene. Homozygote mutations in CTNS are known to cause cystinosis, a disorder characterized by the intralysosomal accumulation of cystine in all tissues. We present the first CNV results in individuals presenting AGD and a possible candidate gene implicated in the disorder.

  16. A functional variant in MIR137, a candidate gene for schizophrenia, affects Stroop test performance in young adults.

    Science.gov (United States)

    González-Giraldo, Yeimy; González-Reyes, Rodrigo E; Forero, Diego A

    2016-02-28

    MIR137, a brain expressed miRNA, has been identified as a top novel susceptibility gene for schizophrenia (SZ). 230 healthy participants completed the Stroop test and were genotyped for a functional Variable Number Tandem Repeat (VNTR) in MIR137 gene. MIR137 VNTR genotypes were associated with differences in Stroop facilitation and accuracies in congruent trials and for the total number of errors. This is the first study of the functional VNTR in MIR137 gene and Stroop test performance in healthy subjects. Our results could have important implications for the identification of genetic candidates for endophenotypes for SZ.

  17. EMP3 methylation and expression analysis and evaluation as a putative tumour suppressor gene located at 19q13.3 in human gliomas

    OpenAIRE

    Kunitz, Annegret

    2010-01-01

    Allelic losses on 19q are found in the majority of oligodendroglial tumors and approximately one-third of diffuse astrocytomas. However, the tumor suppressor genes (TSG) on 19q are still elusive. Using cDNA microarray expression profiling, EMP3 at 19q13.3 was among those genes showing the most pronounced expression differences. In line with this, other authors reported EMP3 as being epigenetically silenced in neuroblastomas and astrocytomas. To further investigate EMP3 as a TSG candidate on 1...

  18. Lactobacillus plantarum gene clusters encoding putative cell-surface protein complexes for carbohydrate utilization are conserved in specific gram-positive bacteria

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    Muscariello Lidia

    2006-05-01

    Full Text Available Abstract Background Genomes of gram-positive bacteria encode many putative cell-surface proteins, of which the majority has no known function. From the rapidly increasing number of available genome sequences it has become apparent that many cell-surface proteins are conserved, and frequently encoded in gene clusters or operons, suggesting common functions, and interactions of multiple components. Results A novel gene cluster encoding exclusively cell-surface proteins was identified, which is conserved in a subgroup of gram-positive bacteria. Each gene cluster generally has one copy of four new gene families called cscA, cscB, cscC and cscD. Clusters encoding these cell-surface proteins were found only in complete genomes of Lactobacillus plantarum, Lactobacillus sakei, Enterococcus faecalis, Listeria innocua, Listeria monocytogenes, Lactococcus lactis ssp lactis and Bacillus cereus and in incomplete genomes of L. lactis ssp cremoris, Lactobacillus casei, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillius brevis, Oenococcus oeni, Leuconostoc mesenteroides, and Bacillus thuringiensis. These genes are neither present in the genomes of streptococci, staphylococci and clostridia, nor in the Lactobacillus acidophilus group, suggesting a niche-specific distribution, possibly relating to association with plants. All encoded proteins have a signal peptide for secretion by the Sec-dependent pathway, while some have cell-surface anchors, novel WxL domains, and putative domains for sugar binding and degradation. Transcriptome analysis in L. plantarum shows that the cscA-D genes are co-expressed, supporting their operon organization. Many gene clusters are significantly up-regulated in a glucose-grown, ccpA-mutant derivative of L. plantarum, suggesting catabolite control. This is supported by the presence of predicted CRE-sites upstream or inside the up-regulated cscA-D gene clusters. Conclusion We propose that the CscA, CscB, CscC and Csc

  19. Mating type gene homologues and putative sex pheromone-sensing pathway in arbuscular mycorrhizal fungi, a presumably asexual plant root symbiont.