WorldWideScience

Sample records for replication genetic analysis

  1. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2001-01-01

    The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

  2. Genetic analysis without replications: Model evaluation and application in spring wheat

    Science.gov (United States)

    Genetic data collected from plant breeding and genetic studies may not be replicated in field designs even though field variation is present. In this study, we addressed this problem using spring wheat (Triticum eastivum L.) trial data collected from two locations. There were no intra-location repl...

  3. Molecular genetic analysis of a vaccinia virus gene with an essential role in DNA replication

    International Nuclear Information System (INIS)

    Evans, E.V.A.

    1989-01-01

    The poxvirus, vaccinia, is large DNA virus which replicates in the cytoplasma of the host cell. The virus is believed to encode most or all of the functions required for the temporally regulated transcription and replication of its 186 kilobase genome. Physical and genetic autonomy from the host make vaccinia a useful eukaryotic organism in which to study replication genes and proteins, using a combination of biochemical and genetic techniques. Essential viral functions for replication are identified by conditional lethal mutants that fail to synthesize DNA at the non-permissive temperatures. One such group contains the non-complementing alleles ts17, ts24, ts69 (WR strain). Studies were undertaken to define the phenotype of ts mutants, and to identify and characterize the affected gene and protein. Mutant infection was essentially normal at 32 degree C, but at 39 degree C the mutants did not incorporate 3 H-thymidine into nascent viral DNA or synthesize late viral proteins. If mutant cultures were shifted to non-permissive conditions at the height of replication, DNA synthesis was halted rapidly, implying that the mutants are defective in DNA elongation. The gene affected in the WR mutants and in ts6389, a DNA-minus mutant of the IHD strain, was mapped by marker rescue and corresponds to open reading frame 5 (orfD5) of the viral HindIII D fragment

  4. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

    NARCIS (Netherlands)

    Santure, Anna W.; Poissant, Jocelyn; Cauwer, De Isabelle; Oers, Van Kees; Robinson, Matthew R.; Quinn, John L.; Groenen, M.A.M.; Visser, M.E.; Sheldon, Ben C.; Slate, Jon

    2015-01-01

    Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar

  5. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

    NARCIS (Netherlands)

    Santure, Anna W; Poissant, Jocelyn; De Cauwer, Isabelle; van Oers, Kees; Robinson, Matthew R; Quinn, John L; Groenen, Martien A M; Visser, Marcel E; Sheldon, Ben C; Slate, Jon

    2015-01-01

    Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic

  6. Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

    Science.gov (United States)

    Moayyeri, Alireza; Hsu, Yi-Hsiang; Karasik, David; Estrada, Karol; Xiao, Su-Mei; Nielson, Carrie; Srikanth, Priya; Giroux, Sylvie; Wilson, Scott G.; Zheng, Hou-Feng; Smith, Albert V.; Pye, Stephen R.; Leo, Paul J.; Teumer, Alexander; Hwang, Joo-Yeon; Ohlsson, Claes; McGuigan, Fiona; Minster, Ryan L.; Hayward, Caroline; Olmos, José M.; Lyytikäinen, Leo-Pekka; Lewis, Joshua R.; Swart, Karin M.A.; Masi, Laura; Oldmeadow, Chris; Holliday, Elizabeth G.; Cheng, Sulin; van Schoor, Natasja M.; Harvey, Nicholas C.; Kruk, Marcin; del Greco M, Fabiola; Igl, Wilmar; Trummer, Olivia; Grigoriou, Efi; Luben, Robert; Liu, Ching-Ti; Zhou, Yanhua; Oei, Ling; Medina-Gomez, Carolina; Zmuda, Joseph; Tranah, Greg; Brown, Suzanne J.; Williams, Frances M.; Soranzo, Nicole; Jakobsdottir, Johanna; Siggeirsdottir, Kristin; Holliday, Kate L.; Hannemann, Anke; Go, Min Jin; Garcia, Melissa; Polasek, Ozren; Laaksonen, Marika; Zhu, Kun; Enneman, Anke W.; McEvoy, Mark; Peel, Roseanne; Sham, Pak Chung; Jaworski, Maciej; Johansson, Åsa; Hicks, Andrew A.; Pludowski, Pawel; Scott, Rodney; Dhonukshe-Rutten, Rosalie A.M.; van der Velde, Nathalie; Kähönen, Mika; Viikari, Jorma S.; Sievänen, Harri; Raitakari, Olli T.; González-Macías, Jesús; Hernández, Jose L.; Mellström, Dan; Ljunggren, Östen; Cho, Yoon Shin; Völker, Uwe; Nauck, Matthias; Homuth, Georg; Völzke, Henry; Haring, Robin; Brown, Matthew A.; McCloskey, Eugene; Nicholson, Geoffrey C.; Eastell, Richard; Eisman, John A.; Jones, Graeme; Reid, Ian R.; Dennison, Elaine M.; Wark, John; Boonen, Steven; Vanderschueren, Dirk; Wu, Frederick C.W.; Aspelund, Thor; Richards, J. Brent; Bauer, Doug; Hofman, Albert; Khaw, Kay-Tee; Dedoussis, George; Obermayer-Pietsch, Barbara; Gyllensten, Ulf; Pramstaller, Peter P.; Lorenc, Roman S.; Cooper, Cyrus; Kung, Annie Wai Chee; Lips, Paul; Alen, Markku; Attia, John; Brandi, Maria Luisa; de Groot, Lisette C.P.G.M.; Lehtimäki, Terho; Riancho, José A.; Campbell, Harry; Liu, Yongmei; Harris, Tamara B.; Akesson, Kristina; Karlsson, Magnus; Lee, Jong-Young; Wallaschofski, Henri; Duncan, Emma L.; O'Neill, Terence W.; Gudnason, Vilmundur; Spector, Timothy D.; Rousseau, François; Orwoll, Eric; Cummings, Steven R.; Wareham, Nick J.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Prince, Richard L.; Kiel, Douglas P.; Reeve, Jonathan; Kaptoge, Stephen K.

    2014-01-01

    Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10−8) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10−14). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10−6 also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology. PMID:24430505

  7. Network Approach to Understanding Emotion Dynamics in Relation to Childhood Trauma and Genetic Liability to Psychopathology: Replication of a Prospective Experience Sampling Analysis

    Directory of Open Access Journals (Sweden)

    Laila Hasmi

    2017-11-01

    present findings demonstrate that the network approach may have some value in understanding the relation between established risk factors for mental disorders (particularly GL and the dynamic interplay between emotions. The present finding partially replicates an earlier analysis, suggesting it may be instructive to model negative emotional dynamics as a function of genetic influence.

  8. Replication of genetic associations as pseudoreplication due to shared genealogy.

    Science.gov (United States)

    Rosenberg, Noah A; Vanliere, Jenna M

    2009-09-01

    The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

  9. Genetic analysis

    NARCIS (Netherlands)

    Koornneef, M.; Alonso-Blanco, C.; Stam, P.

    2006-01-01

    The Mendelian analysis of genetic variation, available as induced mutants or as natural variation, requires a number of steps that are described in this chapter. These include the determination of the number of genes involved in the observed trait's variation, the determination of dominance

  10. Riverscape genetics identifies replicated ecological divergence across an Amazonian ecotone.

    Science.gov (United States)

    Cooke, Georgina M; Landguth, Erin L; Beheregaray, Luciano B

    2014-07-01

    Ecological speciation involves the evolution of reproductive isolation and niche divergence in the absence of a physical barrier to gene flow. The process is one of the most controversial topics of the speciation debate, particularly in tropical regions. Here, we investigate ecologically based divergence across an Amazonian ecotone in the electric fish, Steatogenys elegans. We combine phylogenetics, genome scans, and population genetics with a recently developed individual-based evolutionary landscape genetics approach that incorporates selection. This framework is used to assess the relative contributions of geography and divergent natural selection between environments as biodiversity drivers. We report on two closely related and sympatric lineages that exemplify how divergent selection across a major Amazonian aquatic ecotone (i.e., between rivers with markedly different hydrochemical properties) may result in replicated ecologically mediated speciation. The results link selection across an ecological gradient with reproductive isolation and we propose that assortative mating based on water color may be driving the divergence. Divergence resulting from ecologically driven selection highlights the importance of considering environmental heterogeneity in studies of speciation in tropical regions. Furthermore, we show that framing ecological speciation in a spatially explicit evolutionary landscape genetics framework provides an important first step in exploring a wide range of the potential effects of spatial dependence in natural selection. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  11. Using CSF biomarkers to replicate genetic associations in Alzheimer's disease

    NARCIS (Netherlands)

    Schott, Jonathan M.; Abdi, Hervé; Abdul Hadi, Normi; Abdulkadir, Ahmed; Abdullah, Afnizanfaizal; Achuthan, Anusha; Adluru, Nagesh; Aggarwal, Namita; Aghajanian, Jania; Agyemang, Alex; Ahdidan, Jamila; Ahmad, Duaa; Ahmed, Fayeza; Ahmed, Shiek; Ahmed, Fareed; Akbarifar, Roshanak; Akhondi-Asl, Alireza; Aksu, Yaman; Alcauter, Sarael; Alexander, Daniel; Alin, Aylin; Alshuft, Hamza; Alvarez-Linera, Juan; Amin-Mansour, Ali; Anderson, Jeff; Anderson, Dallas; Andorn, Anne; Andrews, K. Abigail; Ang, Amma; Angersbach, Steve; Ansarian, Reza; Abhishek, Appaji M.; Appannah, Arti; Arfanakis, Konstantinos; Arif, Muhammad; Armentrout, Steven; Arrighi, Michael; Arumughababu, S. Vethanayaki; Arunagiri, Vidhya; Ashe-McNalley, Cody; Ashford, Wes; Le Page, Aurelie; Avants, Brian; Aviv, Richard; Avula, Ramesh; Ayache, Nicholas; Ayan-Oshodi, Mosun; Ayhan, Murat; Richard, Edo; Schmand, Ben

    2012-01-01

    Defining cases and controls on the basis of biomarkers rather than clinical diagnosis may reduce sample sizes required for genetic studies. The aim of this study was to assess whether characterizing case/control status on the basis of cerebrospinal fluid (CSF) profile would increase power to

  12. Climate variables explain neutral and adaptive variation within salmonid metapopulations: The importance of replication in landscape genetics

    Science.gov (United States)

    Hand, Brian K.; Muhlfeld, Clint C.; Wade, Alisa A.; Kovach, Ryan; Whited, Diane C.; Narum, Shawn R.; Matala, Andrew P.; Ackerman, Michael W.; Garner, B. A.; Kimball, John S; Stanford, Jack A.; Luikart, Gordon

    2016-01-01

    Understanding how environmental variation influences population genetic structure is important for conservation management because it can reveal how human stressors influence population connectivity, genetic diversity and persistence. We used riverscape genetics modelling to assess whether climatic and habitat variables were related to neutral and adaptive patterns of genetic differentiation (population-specific and pairwise FST) within five metapopulations (79 populations, 4583 individuals) of steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, USA. Using 151 putatively neutral and 29 candidate adaptive SNP loci, we found that climate-related variables (winter precipitation, summer maximum temperature, winter highest 5% flow events and summer mean flow) best explained neutral and adaptive patterns of genetic differentiation within metapopulations, suggesting that climatic variation likely influences both demography (neutral variation) and local adaptation (adaptive variation). However, we did not observe consistent relationships between climate variables and FST across all metapopulations, underscoring the need for replication when extrapolating results from one scale to another (e.g. basin-wide to the metapopulation scale). Sensitivity analysis (leave-one-population-out) revealed consistent relationships between climate variables and FST within three metapopulations; however, these patterns were not consistent in two metapopulations likely due to small sample sizes (N = 10). These results provide correlative evidence that climatic variation has shaped the genetic structure of steelhead populations and highlight the need for replication and sensitivity analyses in land and riverscape genetics.

  13. Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

    Directory of Open Access Journals (Sweden)

    Sarit Suissa

    2009-05-01

    Full Text Available Although the functional consequences of mitochondrial DNA (mtDNA genetic backgrounds (haplotypes, haplogroups have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74% and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%. The variant defining Caucasian haplogroup J (C295T increased the binding of TFAM (Electro Mobility Shift Assay and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1, a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mt

  14. Efficient replication of over 180 genetic associations with self-reported medical data.

    Science.gov (United States)

    Tung, Joyce Y; Do, Chuong B; Hinds, David A; Kiefer, Amy K; Macpherson, J Michael; Chowdry, Arnab B; Francke, Uta; Naughton, Brian T; Mountain, Joanna L; Wojcicki, Anne; Eriksson, Nicholas

    2011-01-01

    While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations.

  15. Efficient replication of over 180 genetic associations with self-reported medical data.

    Directory of Open Access Journals (Sweden)

    Joyce Y Tung

    Full Text Available While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence. Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations.

  16. Effects of Replication and Transcription on DNA Structure-Related Genetic Instability.

    Science.gov (United States)

    Wang, Guliang; Vasquez, Karen M

    2017-01-05

    Many repetitive sequences in the human genome can adopt conformations that differ from the canonical B-DNA double helix (i.e., non-B DNA), and can impact important biological processes such as DNA replication, transcription, recombination, telomere maintenance, viral integration, transposome activation, DNA damage and repair. Thus, non-B DNA-forming sequences have been implicated in genetic instability and disease development. In this article, we discuss the interactions of non-B DNA with the replication and/or transcription machinery, particularly in disease states (e.g., tumors) that can lead to an abnormal cellular environment, and how such interactions may alter DNA replication and transcription, leading to potential conflicts at non-B DNA regions, and eventually result in genetic stability and human disease.

  17. Hedge fund replication with a genetic algorithm: breeding a usable mousetrap

    Czech Academy of Sciences Publication Activity Database

    Payne, B. C.; Trešl, Jiří

    2015-01-01

    Roč. 15, č. 10 (2015), s. 1705-1726 ISSN 1469-7688 R&D Projects: GA ČR(CZ) GA14-31783S Institutional support: RVO:67985998 Keywords : hedge funds * replication * genetic algorithm Subject RIV: AH - Economics Impact factor: 0.794, year: 2015

  18. Peer Influence, Genetic Propensity, and Binge Drinking: A Natural Experiment and a Replication.

    Science.gov (United States)

    Guo, Guang; Li, Yi; Wang, Hongyu; Cai, Tianji; Duncan, Greg J

    2015-11-01

    The authors draw data from the College Roommate Study (ROOM) and the National Longitudinal Study of Adolescent Health to investigate gene-environment interaction effects on youth binge drinking. In ROOM, the environmental influence was measured by the precollege drinking behavior of randomly assigned roommates. Random assignment safeguards against friend selection and removes the threat of gene-environment correlation that makes gene-environment interaction effects difficult to interpret. On average, being randomly assigned a drinking peer as opposed to a nondrinking peer increased college binge drinking by 0.5-1.0 episodes per month, or 20%-40% the average amount of binge drinking. However, this peer influence was found only among youths with a medium level of genetic propensity for alcohol use; those with either a low or high genetic propensity were not influenced by peer drinking. A replication of the findings is provided in data drawn from Add Health. The study shows that gene-environment interaction analysis can uncover social-contextual effects likely to be missed by traditional sociological approaches.

  19. Integrated genetic analysis microsystems

    International Nuclear Information System (INIS)

    Lagally, Eric T; Mathies, Richard A

    2004-01-01

    With the completion of the Human Genome Project and the ongoing DNA sequencing of the genomes of other animals, bacteria, plants and others, a wealth of new information about the genetic composition of organisms has become available. However, as the demand for sequence information grows, so does the workload required both to generate this sequence and to use it for targeted genetic analysis. Microfabricated genetic analysis systems are well poised to assist in the collection and use of these data through increased analysis speed, lower analysis cost and higher parallelism leading to increased assay throughput. In addition, such integrated microsystems may point the way to targeted genetic experiments on single cells and in other areas that are otherwise very difficult. Concomitant with these advantages, such systems, when fully integrated, should be capable of forming portable systems for high-speed in situ analyses, enabling a new standard in disciplines such as clinical chemistry, forensics, biowarfare detection and epidemiology. This review will discuss the various technologies available for genetic analysis on the microscale, and efforts to integrate them to form fully functional robust analysis devices. (topical review)

  20. Genetic exchanges caused by ultraviolet photoproducts in phage lamda DNA molecules: the role of DNA replication

    International Nuclear Information System (INIS)

    Lin, P.F.; Howard-Flanders, P.; Yale Univ., New Haven, Conn.

    1976-01-01

    Genetic recombination induced by structural damage in DNA molecules was investigated in E. coli K12(lamda) lysogens infected with genetically marked phage lamda. Photoproducts were induced in the phage DNA before infection by exposing them either to 313 nm light in the presence of acetophenone or to 254 nm light. To test the role of the replication of the damage phage DNA on the frequency of the induced recombination , both heteroimmune and homoimmune crosses were performed, and scored for P + recombinants. In heteroimmune crosses, recombination was less frequent in infected cells exposed to visible light and in wild type cells able to perform excision repair than in excision-defective lysogens. Therefore, much of the induced recombination can be attributed to the pyrimidine dimers in the phage DNA. In homoimmune crosses, replication of the phage DNA containing ultraviolet photoproducts was represented by lamda immunity, and was further blocked by the lack of the P gene product needed for replication. The 254 nm photoproducts increased the frequency of recombination in these homoimmune crosses, even though phage DNA replication was blocked. Irradiation with 313 nm light and acetophenone M, which produces dimers and unknown photoproducts, was not as effective per dimer as the 254 nm light. It is concluded from these results that certain unidentified 254 nm photoproducts can cause recombination even in the absence of DNA replication. They are not pyrimidine dimers, as they are not susceptible to excision repair or photoreactivation. In contrast, pyrimidine dimers appear to cause recombination only when the DNA containing them undergoes replication. (orig./MG) [de

  1. Genetic recombination in escherichia coli and its relationship with DNA replication

    International Nuclear Information System (INIS)

    Siddiqui, O.

    1974-01-01

    Relationship of DNA replication with genetic recombination in Escherichia Coli was investigated by mating Hfr donors labelled with H 3 -thymine, C 13 and N 15 to C 13 N 15 labelled recipients. The DNA extracted from the zygotes was analysed on CsCl density gradients. The results show that all of the biparentally labelled DNA arises from the single strand insertions of the donor DNA. (M.G.B.)

  2. Genome-scale cluster analysis of replicated microarrays using shrinkage correlation coefficient.

    Science.gov (United States)

    Yao, Jianchao; Chang, Chunqi; Salmi, Mari L; Hung, Yeung Sam; Loraine, Ann; Roux, Stanley J

    2008-06-18

    Currently, clustering with some form of correlation coefficient as the gene similarity metric has become a popular method for profiling genomic data. The Pearson correlation coefficient and the standard deviation (SD)-weighted correlation coefficient are the two most widely-used correlations as the similarity metrics in clustering microarray data. However, these two correlations are not optimal for analyzing replicated microarray data generated by most laboratories. An effective correlation coefficient is needed to provide statistically sufficient analysis of replicated microarray data. In this study, we describe a novel correlation coefficient, shrinkage correlation coefficient (SCC), that fully exploits the similarity between the replicated microarray experimental samples. The methodology considers both the number of replicates and the variance within each experimental group in clustering expression data, and provides a robust statistical estimation of the error of replicated microarray data. The value of SCC is revealed by its comparison with two other correlation coefficients that are currently the most widely-used (Pearson correlation coefficient and SD-weighted correlation coefficient) using statistical measures on both synthetic expression data as well as real gene expression data from Saccharomyces cerevisiae. Two leading clustering methods, hierarchical and k-means clustering were applied for the comparison. The comparison indicated that using SCC achieves better clustering performance. Applying SCC-based hierarchical clustering to the replicated microarray data obtained from germinating spores of the fern Ceratopteris richardii, we discovered two clusters of genes with shared expression patterns during spore germination. Functional analysis suggested that some of the genetic mechanisms that control germination in such diverse plant lineages as mosses and angiosperms are also conserved among ferns. This study shows that SCC is an alternative to the Pearson

  3. A replication of a factor analysis of motivations for trapping

    Science.gov (United States)

    Schroeder, Susan; Fulton, David C.

    2015-01-01

    Using a 2013 sample of Minnesota trappers, we employed confirmatory factor analysis to replicate an exploratory factor analysis of trapping motivations conducted by Daigle, Muth, Zwick, and Glass (1998).  We employed the same 25 items used by Daigle et al. and tested the same five-factor structure using a recent sample of Minnesota trappers. We also compared motivations in our sample to those reported by Daigle et el.

  4. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus.

    Science.gov (United States)

    Lin, Chia-Chi; Yang, Zhi-Wei; Iang, Shan-Bei; Chao, Mei

    2015-01-02

    Hepatitis delta virus (HDV) replication is carried out by host RNA polymerases. Since homologous inter-genotypic RNA recombination is known to occur in HDV, possibly via a replication-dependent process, we hypothesized that the degree of sequence homology and the replication level should be related to the recombination frequency in cells co-expressing two HDV sequences. To confirm this, we separately co-transfected cells with three different pairs of HDV genomic RNAs and analyzed the obtained recombinants by RT-PCR followed by restriction fragment length polymorphism and sequencing analyses. The sequence divergence between the clones ranged from 24% to less than 0.1%, and the difference in replication levels was as high as 100-fold. As expected, significant differences were observed in the recombination frequencies, which ranged from 0.5% to 47.5%. Furthermore, varying the relative amounts of parental RNA altered the dominant recombinant species produced, suggesting that template switching occurs frequently during the synthesis of genomic HDV RNA. Taken together, these data suggest that during the host RNA polymerase-driven RNA recombination of HDV, both inter- and intra-genotypic recombination events are important in shaping the genetic diversity of HDV. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Szalewska-Pałasz Agnieszka

    2011-03-01

    Full Text Available Abstract Background Until now, the direct link between central carbon metabolism and DNA replication has been demonstrated only in Bacillus. subtilis. Therefore, we asked if this is a specific phenomenon, characteristic for this bacterium and perhaps for its close relatives, or a more general biological rule. Results We found that temperature-sensitivity of mutants in particular genes coding for replication proteins could be suppressed by deletions of certain genes coding for enzymes of the central carbon metabolism. Namely, the effects of dnaA46(ts mutation could be suppressed by dysfunction of pta or ackA, effects of dnaB(ts by dysfunction of pgi or pta, effects of dnaE486(ts by dysfunction of tktB, effects of dnaG(ts by dysfunction of gpmA, pta or ackA, and effects of dnaN159(ts by dysfunction of pta or ackA. The observed suppression effects were not caused by a decrease in bacterial growth rate. Conclusions The genetic correlation exists between central carbon metabolism and DNA replication in the model Gram-negative bacterium, E. coli. This link exists at the steps of initiation and elongation of DNA replication, indicating the important global correlation between metabolic status of the cell and the events leading to cell reproduction.

  6. Analytical strategies for discovery and replication of genetic effects in pharmacogenomic studies

    Directory of Open Access Journals (Sweden)

    Kohler JR

    2014-08-01

    Full Text Available Jared R Kohler, Tobias Guennel, Scott L MarshallBioStat Solutions, Inc., Frederick, MD, USAAbstract: In the past decade, the pharmaceutical industry and biomedical research sector have devoted considerable resources to pharmacogenomics (PGx with the hope that understanding genetic variation in patients would deliver on the promise of personalized medicine. With the advent of new technologies and the improved collection of DNA samples, the roadblock to advancements in PGx discovery is no longer the lack of high-density genetic information captured on patient populations, but rather the development, adaptation, and tailoring of analytical strategies to effectively harness this wealth of information. The current analytical paradigm in PGx considers the single-nucleotide polymorphism (SNP as the genomic feature of interest and performs single SNP association tests to discover PGx effects – ie, genetic effects impacting drug response. While it can be straightforward to process single SNP results and to consider how this information may be extended for use in downstream patient stratification, the rate of replication for single SNP associations has been low and the desired success of producing clinically and commercially viable biomarkers has not been realized. This may be due to the fact that single SNP association testing is suboptimal given the complexities of PGx discovery in the clinical trial setting, including: 1 relatively small sample sizes; 2 diverse clinical cohorts within and across trials due to genetic ancestry (potentially impacting the ability to replicate findings; and 3 the potential polygenic nature of a drug response. Subsequently, a shift in the current paradigm is proposed: to consider the gene as the genomic feature of interest in PGx discovery. The proof-of-concept study presented in this manuscript demonstrates that genomic region-based association testing has the potential to improve the power of detecting single SNP or

  7. Replication analysis of genetic association of the NCAN-CILP2 region with plasma lipid levels and non-alcoholic fatty liver disease in Asian and Pacific ethnic groups.

    Science.gov (United States)

    Boonvisut, Supichaya; Nakayama, Kazuhiro; Makishima, Saho; Watanabe, Kazuhisa; Miyashita, Hiroshi; Lkhagvasuren, Munkhtulga; Kagawa, Yasuo; Iwamoto, Sadahiko

    2016-01-13

    The Neurocan-cartilage intermediate layer protein 2 (NCAN-CILP2) region forms a tight linkage disequilibrium (LD) block and is associated with plasma lipid levels and non-alcoholic fatty liver disease (NAFLD) in individuals of European descent but not in the Malay and Japanese ethnic groups. Recent genome-wide resequence studies identified a missense single-nucleotide polymorphism (SNP) (rs58542926) of the transmembrane 6 superfamily member 2 (TM6SF2) gene in the NCAN-CILP2 region related to hepatic triglyceride content. This study aims to analyze the influences of SNPs in this region on NAFLD and plasma lipid levels in the Asian and Pacific ethnic groups and to reveal the reasons behind positive and negative genetic associations dependent on ethnicity. Samples and characteristic data were collected from 3,013 Japanese, 119 Palauan, 947 Mongolian, 212 Thai and 401 Chinese people. Hepatic sonography data was obtained from the Japanese individuals. Genotyping data of five SNPs, rs58542926, rs735273, rs1009136, rs1858999, and rs16996148, were used to verify the effect on serum lipid levels by multiple linear regression, and the association with NAFLD in the Japanese population was examined by logistic regression analysis. rs58542926 showed significant association with the plasma triglyceride (TG) level in Japanese (P = 0.0009, effect size = 9.5 (± 3.25) mg/dl/allele) and Thai (P = 0.0008, effect size = 31.6 (± 11.7) mg/dl/allele) study subjects. In Mongolian individuals, there was a significant association of rs58542926 with total cholesterol level (P = 0.0003, 11.7 (± 3.2) mg/dl/allele) but not with TG level. In multiple comparisons in Chinese individuals, rs58542926 was weakly (P = 0.022) associated with TG levels, although the threshold for statistical significance was not reached. In Palauan individuals, there was no significant association with the studied SNPs. rs58542926 also showed significant association with Japanese NAFLD. The minor allele (t) increased

  8. Genetic influences on hand osteoarthritis in Finnish women--a replication study of candidate genes.

    Directory of Open Access Journals (Sweden)

    Satu Hämäläinen

    Full Text Available OBJECTIVES: Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs in five genes (A2BP1, COG5, GDF5, HFE, ESR1 with hand osteoarthritis (OA, and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1 associated with OA at other joint sites were associated with hand OA among Finnish women. DESIGN: We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression. RESULTS: Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5-0.9 and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2-2.9. We found an interaction between ESR1 (rs9340799 and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3-6.5. We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1-6.1. There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3-2.5. CONCLUSIONS: Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.

  9. One for all and all for One: Improving replication of genetic studies through network diffusion.

    Directory of Open Access Journals (Sweden)

    Daniel Lancour

    2018-04-01

    Full Text Available Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.

  10. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

    Directory of Open Access Journals (Sweden)

    Omri Gottesman

    Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  11. COMPUTER METHODS OF GENETIC ANALYSIS.

    Directory of Open Access Journals (Sweden)

    A. L. Osipov

    2017-02-01

    Full Text Available The basic statistical methods used in conducting the genetic analysis of human traits. We studied by segregation analysis, linkage analysis and allelic associations. Developed software for the implementation of these methods support.

  12. Molecular analysis of the replication program in unicellular model organisms.

    Science.gov (United States)

    Raghuraman, M K; Brewer, Bonita J

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

  13. Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

    Directory of Open Access Journals (Sweden)

    Helen Fox

    2017-01-01

    Full Text Available While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.

  14. Molecular analysis of the replication program in unicellular model organisms

    OpenAIRE

    Raghuraman, M. K.; Brewer, Bonita J.

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program o...

  15. Genetic Moderation of Stability in Attachment Security from Early Childhood to Age 18 Years: A Replication Study

    Science.gov (United States)

    Raby, K. Lee; Roisman, Glenn I.; Booth-LaForce, Cathryn

    2015-01-01

    A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin…

  16. Reverse Genetics System Demonstrates that Rotavirus Nonstructural Protein NSP6 Is Not Essential for Viral Replication in Cell Culture.

    Science.gov (United States)

    Komoto, Satoshi; Kanai, Yuta; Fukuda, Saori; Kugita, Masanori; Kawagishi, Takahiro; Ito, Naoto; Sugiyama, Makoto; Matsuura, Yoshiharu; Kobayashi, Takeshi; Taniguchi, Koki

    2017-11-01

    The use of overlapping open reading frames (ORFs) to synthesize more than one unique protein from a single mRNA has been described for several viruses. Segment 11 of the rotavirus genome encodes two nonstructural proteins, NSP5 and NSP6. The NSP6 ORF is present in the vast majority of rotavirus strains, and therefore the NSP6 protein would be expected to have a function in viral replication. However, there is no direct evidence of its function or requirement in the viral replication cycle yet. Here, taking advantage of a recently established plasmid-only-based reverse genetics system that allows rescue of recombinant rotaviruses entirely from cloned cDNAs, we generated NSP6-deficient viruses to directly address its significance in the viral replication cycle. Viable recombinant NSP6-deficient viruses could be engineered. Single-step growth curves and plaque formation of the NSP6-deficient viruses confirmed that NSP6 expression is of limited significance for RVA replication in cell culture, although the NSP6 protein seemed to promote efficient virus growth. IMPORTANCE Rotavirus is one of the most important pathogens of severe diarrhea in young children worldwide. The rotavirus genome, consisting of 11 segments of double-stranded RNA, encodes six structural proteins (VP1 to VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6). Although specific functions have been ascribed to each of the 12 viral proteins, the role of NSP6 in the viral replication cycle remains unknown. In this study, we demonstrated that the NSP6 protein is not essential for viral replication in cell culture by using a recently developed plasmid-only-based reverse genetics system. This reverse genetics approach will be successfully applied to answer questions of great interest regarding the roles of rotaviral proteins in replication and pathogenicity, which can hardly be addressed by conventional approaches. Copyright © 2017 American Society for Microbiology.

  17. Repeatability study of replicate crash tests: A signal analysis approach.

    Science.gov (United States)

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

    2017-10-03

    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

  18. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

    LENUS (Irish Health Repository)

    Trompet, Stella

    2011-10-06

    Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER\\/PHASE project and second show that the PROSPER\\/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer\\'s instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE\\/APOC1; LDLR; FADS2\\/FEN1; HMGCR; PSRC1\\/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER\\/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  19. Electron microscopic analysis of rotavirus assembly-replication intermediates

    International Nuclear Information System (INIS)

    Boudreaux, Crystal E.; Kelly, Deborah F.; McDonald, Sarah M.

    2015-01-01

    Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy

  20. Electron microscopic analysis of rotavirus assembly-replication intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Boudreaux, Crystal E.; Kelly, Deborah F. [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); McDonald, Sarah M., E-mail: mcdonaldsa@vtc.vt.edu [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); Department of Biomedical Sciences and Pathobiology, Virginia—Maryland Regional College of Veterinary Medicine, Blacksburg, VA (United States)

    2015-03-15

    Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy.

  1. Functional analysis of replication determinantsin classical swine fever virus

    DEFF Research Database (Denmark)

    Hadsbjerg, Johanne

    and animal pathogens should facilitate finding new approaches for efficient disease control. The principal aim of this thesis is to characterise determinants involved in the replication of classical swine fever virus (CSFV). Classical swine fever is a highly contagious virus disease of domestic pigs and wild...... in cell culture. Knowledge of these sequence variations and putative long-range interactions will provide valuable insights into mechanisms underlying virustranslation and replication. In manuscript 3, a selection marker has been inserted into a CSFV-based replicon making it suitable for screening...

  2. Mathematical Analysis of Replication by Cash Flow Matching

    Directory of Open Access Journals (Sweden)

    Jan Natolski

    2017-02-01

    Full Text Available The replicating portfolio approach is a well-established approach carried out by many life insurance companies within their Solvency II framework for the computation of risk capital. In this note,weelaborateononespecificformulationofareplicatingportfolioproblem. Incontrasttothetwo most popular replication approaches, it does not yield an analytic solution (if, at all, a solution exists andisunique. Further,althoughconvex,theobjectivefunctionseemstobenon-smooth,andhencea numericalsolutionmightthusbemuchmoredemandingthanforthetwomostpopularformulations. Especially for the second reason, this formulation did not (yet receive much attention in practical applications, in contrast to the other two formulations. In the following, we will demonstrate that the (potential non-smoothness can be avoided due to an equivalent reformulation as a linear second order cone program (SOCP. This allows for a numerical solution by efficient second order methods like interior point methods or similar. We also show that—under weak assumptions—existence and uniqueness of the optimal solution can be guaranteed. We additionally prove that—under a further similarly weak condition—the fair value of the replicating portfolio equals the fair value of liabilities. Based on these insights, we argue that this unloved stepmother child within the replication problem family indeed represents an equally good formulation for practical purposes.

  3. Surface topography analysis for dimensional quality control of replication at the micrometre scale

    DEFF Research Database (Denmark)

    Balcon, M.; Marinello, F.; Tosello, Guido

    2011-01-01

    Replication of geometrical features and surfaces are present at different production levels, from realization of moulds to final product. Geometrical features must be reproduced within specification limits, to ensure product functionality . In order to control the replication quality, mould...... and replica surfaces must be quantitatively analysed and compared. In the present work, reference simulated surfaces were considered and studied in order to evaluate the effectiveness and traceability of different analysis tools for replication quality control. Topographies were analysed simulating different...

  4. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2002-01-01

    .... We have shown that a 5.8 kb DNA fragment containing the initiation region (IR) DHFR ori-beta is active at ectopic chromosomal locations in hamster cells and that deletion of three specific elements in ori-beta reduced initiation activity...

  5. Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

    Science.gov (United States)

    Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

    2016-09-01

    Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity

  6. Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential.

    Science.gov (United States)

    Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

    2018-04-01

    Human papillomaviruses (HPVs) encompass a large family of viruses that range from benign to highly carcinogenic. The crucial differences between benign and carcinogenic types of HPV remain unknown, except that the two HPV types differ in the frequency of DNA replication. We have systematically analyzed the mechanism of HPV DNA replication initiation in low-risk and high-risk HPVs. Our results demonstrate that HPV-encoded E2 initiator protein and its four binding sites in the replication origin play pivotal roles in determining the destiny of the HPV-infected cell. We have identified strain-specific single nucleotide variations in E2 binding sites found only in the high-risk HPVs. We have demonstrated that these variations result in attenuated formation of the E2-DNA complex. E2 binding to these sites is linked to the activation of the DNA replication origin as well as initiation of DNA replication. Both electrophoretic mobility shift assay and atomic force microscopy studies demonstrated that binding of E2 from either low- or high-risk HPVs with variant binding sequences lacked multimeric E2-DNA complex formation in vitro. These results provided a molecular basis of differential DNA replication in the two types of HPVs and pointed to a correlation with the development of cancer. Copyright © 2017. Published by Elsevier B.V.

  7. Stochastic Petri net analysis of a replicated file system

    Science.gov (United States)

    Bechta Dugan, Joanne; Ciardo, Gianfranco

    1989-01-01

    A stochastic Petri-net model of a replicated file system is presented for a distributed environment where replicated files reside on different hosts and a voting algorithm is used to maintain consistency. Witnesses, which simply record the status of the file but contain no data, can be used in addition to or in place of files to reduce overhead. A model sufficiently detailed to include file status (current or out-of-date), as well as failure and repair of hosts where copies or witnesses reside, is presented. The number of copies and witnesses is a parameter of the model. Two different majority protocols are examined, one where a majority of all copies and witnesses is necessary to form a quorum, and the other where only a majority of the copies and witnesses on operational hosts is needed. The latter, known as adaptive voting, is shown to increase file availability in most cases.

  8. Attitudes towards genetic testing: analysis of contradictions

    DEFF Research Database (Denmark)

    Jallinoja, P; Hakonen, A; Aro, A R

    1998-01-01

    A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice and o...... studies on attitudes towards genetic testing as well as in the health care context, e.g. in genetic counselling.......A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice...... and on the confidence in control of the process of genetic testing and its implications. Our analysis indicated that some of the respondents have contradictory attitudes towards genetic testing. It is proposed that contradictory attitudes towards genetic testing should be given greater significance both in scientific...

  9. Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

    NARCIS (Netherlands)

    Kremer, P.H.; Koeleman, B.P.C.; Rinkel, G.J.; Diekstra, F.P.; Berg, L.H. van den; Veldink, J.H.; Klijn, C.J.M.

    2016-01-01

    BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations

  10. Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.

    Science.gov (United States)

    Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

    2017-12-07

    Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer

  11. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

    ... NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team identified 42 new ... Edition Distracted Driving Raises Crash Risk Arthritis Genetics Analysis Aids Drug Discovery Oxytocin Affects Facial Recognition Connect with Us ...

  12. Evaluating the reproducibility of environmental radioactivity monitoring data through replicate sample analysis

    International Nuclear Information System (INIS)

    Lindeken, C.L.; White, J.H.; Silver, W.J.

    1978-01-01

    At the Lawrence Livermore Laboratory, about 10% of the sampling effort in the environmental monitoring program represents replicate sample collection. Replication of field samples was initiated as part of the quality assurance program for environmental monitoring to determine the reproducibility of environmental measurements. In the laboratory these replicates are processed along with routine samples. As all components of variance are included in analysis of such field samples, comparison of the analytical data from replicate analyses provides a basis for estimating the overall reproducibility of the measurements. The replication study indicates that the reproducibility of environmental radioactivity monitoring data is subject to considerably more variability than is indicated by the accompanying counting errors. The data are also compared with analyses of duplicate aliquots from a well mixed sample or with duplicate aliquots of samples with known radionuclide content. These comparisons show that most of the variability is associated with the collection and preparation of the sample rather than with the analytical procedures

  13. An analysis of food irradiation : genetic effects

    International Nuclear Information System (INIS)

    MacPhee, D.; Hall, W.

    1988-01-01

    A series of studies undertaken at the National Institute of Nutrition (NIN) in India in the 1970s reported the occurrence of polyploidy in bone-marrow or peripheral lymphocytes in a number of species, including children, fed on freshly irradiated wheat. Opponents of food irradiation use these studies as evidence that genetic damage is caused by the consumption of irradiated food. This review of those NIN studies and of the attempts to replicate them and of two other relevant studies concludes that the claim that consumption of irradiated food causes genetic damage has not been substantiated. Other researchers have been unable to replicate the NIN studies. Polyploidy appears to be a poor indicator of genetic damage and the NIN results are biologically implausible

  14. Population genetic structure in Atlantic and Pacific Ocean common murres (Uria aalge): Natural replicate tests of post-Pleistocene evolution

    Science.gov (United States)

    Morris-Pocock, J. A.; Taylor, S.A.; Birt, T.P.; Damus, M.; Piatt, John F.; Warheit, K.I.; Friesen, Vicki L.

    2008-01-01

    Understanding the factors that influence population differentiation in temperate taxa can be difficult because the signatures of both historic and contemporary demographics are often reflected in population genetic patterns. Fortunately, analyses based on coalescent theory can help untangle the relative influence of these historic and contemporary factors. Common murres (Uria aalge) are vagile seabirds that breed in the boreal and low arctic waters of the Northern Hemisphere. Previous analyses revealed that Atlantic and Pacific populations are genetically distinct; however, less is known about population genetic structure within ocean basins. We employed the mitochondrial control region, four microsatellite loci and four intron loci to investigate population genetic structure throughout the range of common murres. As in previous studies, we found that Atlantic and Pacific populations diverged during the Pleistocene and do not currently exchange migrants. Therefore, Atlantic and Pacific murre populations can be used as natural replicates to test mechanisms of population differentiation. While we found little population genetic structure within the Pacific, we detected significant east-west structuring among Atlantic colonies. The degree that population genetic structure reflected contemporary population demographics also differed between ocean basins. Specifically, while the low levels of population differentiation in the Pacific are at least partially due to high levels of contemporary gene flow, the east-west structuring of populations within the Atlantic appears to be the result of historic fragmentation of populations rather than restricted contemporary gene flow. The contrasting results in the Atlantic and Pacific Oceans highlight the necessity of carefully considering multilocus nonequilibrium population genetic approaches when reconstructing the demographic history of temperate Northern Hemisphere taxa. ?? 2008 The Authors.

  15. Interpretation of genetic association studies: markers with replicated highly significant odds ratios may be poor classifiers.

    Directory of Open Access Journals (Sweden)

    Johanna Jakobsdottir

    2009-02-01

    Full Text Available Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10(-13, 10(-13, and 10(-3, respectively. The area under the ROC curve (AUC is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively, only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms

  16. Self-Organization of Template-Replicating Polymers and the Spontaneous Rise of Genetic Information

    Directory of Open Access Journals (Sweden)

    Jarle Breivik

    2001-11-01

    Full Text Available Abstract: Living systems imply self-reproducing constructs capable of Darwinian evolution. How such dynamics can arise from undirected interactions between simple monomeric objects remains an open question. Here we circumvent difficulties related to the manipulation of chemical interactions, and present a system of ferromagnetic objects that self-organize into template-replicating polymers due to environmental fluctuations in temperature. Initially random sequences of monomers direct the formation of complementary sequences, and structural information is inherited from one structure to another. Selective replication of sequences occurs in dynamic interaction with the environment, and the system demonstrates the fundamental link between thermodynamics, information theory, and life science in an unprecedented manner.

  17. Genetic moderation of effects of maternal sensitivity on girl's age of menarche: Replication of the Manuck et al. study.

    Science.gov (United States)

    Hartman, Sarah; Widaman, Keith F; Belsky, Jay

    2015-08-01

    Manuck, Craig, Flory, Halder, and Ferrell (2011) reported that a theoretically anticipated effect of family rearing on girls' menarcheal age was genetically moderated by two single nucleotide polymorphisms (SNPs) of the estrogen receptor-α gene. We sought to replicate and extend these findings, studying 210 White females followed from birth. The replication was general because a different measure of the rearing environment was used in this inquiry (i.e., maternal sensitivity) than in the prior one (i.e., family cohesion). Extensions of the work included prospective rather than retrospective measurements of the rearing environment, reports of first menstruation within a year of its occurrence rather than decades later, accounting for some heritability of menarcheal age by controlling for maternal age of menarche, and using a new model-fitting approach to competitively compare diathesis-stress versus differential-susceptibility models of Gene × Environment interaction. The replication/extension effort proved successful in the case of both estrogen receptor-α SNPs, with the Gene × Environment interactions principally reflecting diathesis-stress: lower levels of maternal sensitivity predicted earlier age of menarche for girls homozygous for the minor alleles of either SNP but not for girls carrying other genotypes. Results are discussed in light of the new analytic methods adopted.

  18. Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements

    Directory of Open Access Journals (Sweden)

    Modesto Redrejo-Rodríguez

    2017-11-01

    Full Text Available Family B DNA polymerases (PolBs play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB, that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance.

  19. Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials

    NARCIS (Netherlands)

    Foust, C.M.; Preite, V.; Schrey, A.W.; Alvarez, M.; Robertson, M.H.; Verhoeven, K.J.F.; Richards, Christina L.

    2016-01-01

    While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along

  20. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study

    Czech Academy of Sciences Publication Activity Database

    Suarez-Gestal, M.; Calaza, M.; Endreffy, E.; Pullmann, R.; Ordi-Ros, J.; Sebastiani, D.G.; Růžičková, Šárka; Santos, J.M.; Papasteriades, C.; Marchini, M.; Skopouli, F.N.; Suarez, A.; Blanco, F.J.; D'Alfonso, S.; Bijl, M.; Carreira, P.; Witte, T.; Migliaresi, S.; Gomez-Reino, J.J.; Gonzalez, A.

    2009-01-01

    Roč. 11, č. 3 (2009), R69 ISSN 1478-6362 Keywords : Single nucleotide polymorphism susceptibility * sytemic lupus erythematosus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.271, year: 2009

  1. An analysis of the genetic diversity and genetic structure of ...

    African Journals Online (AJOL)

    Scientific approaches to conservation of threatened species depend on a good understanding of the genetic information of wild and artificial population. The genetic diversity and structure analysis of 10 Eucommia ulmoides population was analyzed using inter-simple sequence repeat (ISSR) markers in this paper.

  2. Validation of reported genetic risk factors for periodontitis in a large-scale replication study

    NARCIS (Netherlands)

    Schaefer, A.S.; Bochenek, G.; Manke, T.; Nothnagel, M.; Graetz, C.; Thien, A.; Jockel-Schneider, Y.; Harks, I.; Staufenbiel, I.; Wijmenga, C.; Eberhard, J.; Guzeldemir-Akcakanat, E.; Cine, N.; Folwaczny, M.; Noack, B.; Meyle, J.; Eickholz, P.; Trombelli, L.; Scapoli, C.; Nohutcu, R.; Bruckmann, C.; Doerfer, C.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2013-01-01

    Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

  3. Validation of reported genetic risk factors for periodontitis in a large-scale replication study

    NARCIS (Netherlands)

    Schaefer, Arne S.; Bochenek, Gregor; Manke, Thomas; Nothnagel, Michael; Graetz, Christian; Thien, Anneke; Jockel-Schneider, Yvonne; Harks, Inga; Staufenbiel, Ingmar; Wijmenga, Cisca; Eberhard, Joerg; Guzeldemir-Akcakanat, Esra; Cine, Naci; Folwaczny, Mathias; Noack, Barbara; Meyle, Joerg; Eickholz, Peter; Trombelli, Leonardo; Scapoli, Chiara; Nohutcu, Rahime; Bruckmann, Corinna; Doerfer, Christof; Jepsen, Soren; Loos, Bruno G.; Schreiber, Stefan

    Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

  4. Real option analysis in a replicating portfolio perspective

    NARCIS (Netherlands)

    van Heeswijk, W.J.A.; Joosten, Reinoud A.M.G.; Huisman, Kuno; Bos, Christian

    2013-01-01

    In the last decades, a vast body of literature has arisen on real option analysis (ROA). The use of di¤erent approaches and the often implicit adoption of major assumptions may cause confusion on what ROA precisely entails, or in which situations it may be applied. We assess the �eld of real option

  5. Microsatellite data analysis for population genetics

    Science.gov (United States)

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of ...

  6. The Analysis of Polyploid Genetic Data

    NARCIS (Netherlands)

    Meirmans, P.G.; Liu, S.; van Tienderen, P.H.

    2018-01-01

    Though polyploidy is an important aspect of the evolutionary genetics of both plants and animals, the development of population genetic theory of polyploids has seriously lagged behind that of diploids. This is unfortunate since the analysis of polyploid genetic data—and the interpretation of the

  7. RESEARCH NOTE Molecular genetic analysis of consanguineous ...

    Indian Academy of Sciences (India)

    Navya

    Molecular genetic analysis of consanguineous families with primary microcephaly ... Translational Research Institute, Academic Health System, Hamad Medical ..... bridging the gap between homozygosity mapping and deep sequencing.

  8. The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study

    LENUS (Irish Health Repository)

    Chappell, Sally L

    2011-02-14

    Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

  9. Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

    Science.gov (United States)

    Schielzeth, Holger; Rios Villamil, Alejandro; Burri, Reto

    2018-03-25

    Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations. © 2018 John Wiley & Sons Ltd.

  10. Multiscale analysis of replication technique efficiency for 3D roughness characterization of manufactured surfaces

    Science.gov (United States)

    Jolivet, S.; Mezghani, S.; El Mansori, M.

    2016-09-01

    The replication of topography has been generally restricted to optimizing material processing technologies in terms of statistical and single-scale features such as roughness. By contrast, manufactured surface topography is highly complex, irregular, and multiscale. In this work, we have demonstrated the use of multiscale analysis on replicates of surface finish to assess the precise control of the finished replica. Five commercial resins used for surface replication were compared. The topography of five standard surfaces representative of common finishing processes were acquired both directly and by a replication technique. Then, they were characterized using the ISO 25178 standard and multiscale decomposition based on a continuous wavelet transform, to compare the roughness transfer quality at different scales. Additionally, atomic force microscope force modulation mode was used in order to compare the resins’ stiffness properties. The results showed that less stiff resins are able to replicate the surface finish along a larger wavelength band. The method was then tested for non-destructive quality control of automotive gear tooth surfaces.

  11. Replication protocol analysis: a method for the study of real-world design thinking

    DEFF Research Database (Denmark)

    Galle, Per; Kovacs, L. B.

    1996-01-01

    ’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture......Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication...... the designer’s authentic line of reasoning. To illustrate how RPA can be used, the site planning case is briefly presented, and part of the replicated line of reasoning analysed. One result of the analysis is a glimpse of a ‘logic of design’; another is an insight which sheds new light on Darke’s classical...

  12. A screen for genetic suppressor elements of hepatitis C virus identifies a supercharged protein inhibitor of viral replication.

    Directory of Open Access Journals (Sweden)

    Rudo L Simeon

    Full Text Available Genetic suppressor elements (GSEs are biomolecules derived from a gene or genome of interest that act as transdominant inhibitors of biological functions presumably by disruption of critical biological interfaces. We exploited a cell death reporter cell line for hepatitis C virus (HCV infection, n4mBid, to develop an iterative selection/enrichment strategy for the identification of anti-HCV GSEs. Using this approach, a library of fragments of an HCV genome was screened for sequences that suppress HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 derives from a single-base frameshift of the enhanced green fluorescent protein (eGFP which was used as a filler during fragment cloning. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa ratio of 1.5. We show that B1 expression specifically inhibits HCV replication. In addition, five highly positively charged B1 fragments produced from progressive truncation at the C-terminus all retain the ability to inhibit HCV, suggesting that a high positive charge, rather than a particular motif in B1, likely accounts for B1's anti-HCV activity. Another supercharged protein, +36GFP, was also found to strongly inhibit HCV replication when added to cells at the time of infection. This study reports a new methodology for HCV inhibitor screening and points to the anti-HCV potential of positively charged proteins/peptides.

  13. RepExplore: addressing technical replicate variance in proteomics and metabolomics data analysis.

    Science.gov (United States)

    Glaab, Enrico; Schneider, Reinhard

    2015-07-01

    High-throughput omics datasets often contain technical replicates included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using robust averages may help to reduce the influence of noise on downstream data analysis, the information on the variance across the replicate measurements is lost in the averaging process and therefore typically disregarded in subsequent statistical analyses.We introduce RepExplore, a web-service dedicated to exploit the information captured in the technical replicate variance to provide more reliable and informative differential expression and abundance statistics for omics datasets. The software builds on previously published statistical methods, which have been applied successfully to biomedical omics data but are difficult to use without prior experience in programming or scripting. RepExplore facilitates the analysis by providing a fully automated data processing and interactive ranking tables, whisker plot, heat map and principal component analysis visualizations to interpret omics data and derived statistics. Freely available at http://www.repexplore.tk enrico.glaab@uni.lu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  14. Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

    Science.gov (United States)

    Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

    2015-01-01

    Of critical importance to many of the events underlying transcriptional control of gene expression are modifications to core and linker histones that regulate the accessibility of trans-acting factors to the DNA substrate within the context of chromatin. Likewise, control over the initiation of DNA replication, as well as the ability of the replication machinery to proceed during elongation through the multiple levels of chromatin condensation that are likely to be encountered, is known to involve the creation of chromatin accessibility. In the latter case, chromatin access will likely need to be a transient event so as to prevent total genomic unraveling of the chromatin that would be deleterious to cells. While there are many molecular and biochemical approaches in use to study histone changes and their relationship to transcription and chromatin accessibility, few techniques exist that allow a molecular dissection of the events underlying DNA replication control as it pertains to chromatin changes and accessibility. Here, we outline a novel experimental strategy for addressing the ability of specific proteins to induce large-scale chromatin unfolding (decondensation) in vivo upon site-specific targeting to an engineered locus. Our laboratory has used this powerful system in novel ways to directly address the ability of DNA replication proteins to create chromatin accessibility, and have incorporated modifications to the basic approach that allow for a molecular genetic analysis of the mechanisms and associated factors involved in causing chromatin decondensation by a protein of interest. Alternative approaches involving co-expression of other proteins (competitors or stimulators), concurrent drug treatments, and analysis of co-localizing histone modifications are also addressed, all of which are illustrative of the utility of this experimental system for extending basic findings to physiologically relevant mechanisms. Although used by our group to analyze

  15. Genetic analysis of Schizosaccharomyces pombe

    DEFF Research Database (Denmark)

    Ekwall, Karl; Thon, Genevieve

    2017-01-01

    In this introduction we discuss some basic genetic tools and techniques that are used with the fission yeast Schizosaccharomyces pombe. Genes commonly used for selection or as reporters are discussed, with an emphasis on genes that permit counterselection, intragenic complementation, or colony......-color assays. S. pombe is most stable as a haploid organism. We describe its mating-type system, how to perform genetic crosses and methods for selecting and propagating diploids. We discuss the relative merits of tetrad dissection and random spore preparation in strain construction and genetic analyses...

  16. The Policy Impact of Social Movements: A Replication Through Qualitative Comparative Analysis

    OpenAIRE

    Giugni, Marco; Yamasaki, Sakura

    2009-01-01

    This article reanalyzes the data of a previous study on the policy impact of antinuclear, ecology, and peace movements in three countries with the aim of replicating its findings. Our goal is to see whether using a different analytical technique will yield similar results. The previous study used a regression approach to time-series analysis. Here, we use qualitative comparative analysis (QCA) to analyze the previous study’s data. Specifically, we test the two main hypotheses based on the joi...

  17. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  18. Analysis of genetic diversity inpigeonpeagermplasm using ...

    Indian Academy of Sciences (India)

    Navya

    2016-11-25

    Nov 25, 2016 ... accessions from Orissa (105) and AP (15) do not group with any Indian accessions. ... In the present work, comparison between SSAP and REMAP revealed ... (sequence-specific amplified polymorphism) for genetic analysis of sweet potato. ... Sharma,V.and Nandinemi, M.R. 2014 Assessment of genetic ...

  19. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  20. Why replication is important in landscape genetics: American black bear in the Rocky Mountains

    Science.gov (United States)

    Short, Bull R.A.; Cushman, S.A.; MacE, R.; Chilton, T.; Kendall, K.C.; Landguth, E.L.; Schwartz, Maurice L.; McKelvey, K.; Allendorf, F.W.; Luikart, G.

    2011-01-01

    We investigated how landscape features influence gene flow of black bears by testing the relative support for 36 alternative landscape resistance hypotheses, including isolation by distance (IBD) in each of 12 study areas in the north central U.S. Rocky Mountains. The study areas all contained the same basic elements, but differed in extent of forest fragmentation, altitude, variation in elevation and road coverage. In all but one of the study areas, isolation by landscape resistance was more supported than IBD suggesting gene flow is likely influenced by elevation, forest cover, and roads. However, the landscape features influencing gene flow varied among study areas. Using subsets of loci usually gave models with the very similar landscape features influencing gene flow as with all loci, suggesting the landscape features influencing gene flow were correctly identified. To test if the cause of the variability of supported landscape features in study areas resulted from landscape differences among study areas, we conducted a limiting factor analysis. We found that features were supported in landscape models only when the features were highly variable. This is perhaps not surprising but suggests an important cautionary note – that if landscape features are not found to influence gene flow, researchers should not automatically conclude that the features are unimportant to the species’ movement and gene flow. Failure to investigate multiple study areas that have a range of variability in landscape features could cause misleading inferences about which landscape features generally limit gene flow. This could lead to potentially erroneous identification of corridors and barriers if models are transferred between areas with different landscape characteristics.

  1. Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies.

    Science.gov (United States)

    Walsh, Kyle M; Anderson, Erik; Hansen, Helen M; Decker, Paul A; Kosel, Matt L; Kollmeyer, Thomas; Rice, Terri; Zheng, Shichun; Xiao, Yuanyuan; Chang, Jeffrey S; McCoy, Lucie S; Bracci, Paige M; Wiemels, Joe L; Pico, Alexander R; Smirnov, Ivan; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2013-02-01

    Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes. © 2012 WILEY PERIODICALS, INC.

  2. Developments in statistical analysis in quantitative genetics

    DEFF Research Database (Denmark)

    Sorensen, Daniel

    2009-01-01

    of genetic means and variances, models for the analysis of categorical and count data, the statistical genetics of a model postulating that environmental variance is partly under genetic control, and a short discussion of models that incorporate massive genetic marker information. We provide an overview......A remarkable research impetus has taken place in statistical genetics since the last World Conference. This has been stimulated by breakthroughs in molecular genetics, automated data-recording devices and computer-intensive statistical methods. The latter were revolutionized by the bootstrap...... and by Markov chain Monte Carlo (McMC). In this overview a number of specific areas are chosen to illustrate the enormous flexibility that McMC has provided for fitting models and exploring features of data that were previously inaccessible. The selected areas are inferences of the trajectories over time...

  3. The Analysis of Polyploid Genetic Data.

    Science.gov (United States)

    Meirmans, Patrick G; Liu, Shenglin; van Tienderen, Peter H

    2018-03-16

    Though polyploidy is an important aspect of the evolutionary genetics of both plants and animals, the development of population genetic theory of polyploids has seriously lagged behind that of diploids. This is unfortunate since the analysis of polyploid genetic data-and the interpretation of the results-requires even more scrutiny than with diploid data. This is because of several polyploidy-specific complications in segregation and genotyping such as tetrasomy, double reduction, and missing dosage information. Here, we review the theoretical and statistical aspects of the population genetics of polyploids. We discuss several widely used types of inferences, including genetic diversity, Hardy-Weinberg equilibrium, population differentiation, genetic distance, and detecting population structure. For each, we point out how the statistical approach, expected result, and interpretation differ between different ploidy levels. We also discuss for each type of inference what biases may arise from the polyploid-specific complications and how these biases can be overcome. From our overview, it is clear that the statistical toolbox that is available for the analysis of genetic data is flexible and still expanding. Modern sequencing techniques will soon be able to overcome some of the current limitations to the analysis of polyploid data, though the techniques are lagging behind those available for diploids. Furthermore, the availability of more data may aggravate the biases that can arise, and increase the risk of false inferences. Therefore, simulations such as we used throughout this review are an important tool to verify the results of analyses of polyploid genetic data.

  4. Genetic analysis in Bartter syndrome from India.

    Science.gov (United States)

    Sharma, Pradeep Kumar; Saikia, Bhaskar; Sharma, Rachna; Ankur, Kumar; Khilnani, Praveen; Aggarwal, Vinay Kumar; Cheong, Hae

    2014-10-01

    Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling.

  5. A loss of function analysis of host factors influencing Vaccinia virus replication by RNA interference.

    Directory of Open Access Journals (Sweden)

    Philippa M Beard

    Full Text Available Vaccinia virus (VACV is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.

  6. Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans.

    Directory of Open Access Journals (Sweden)

    Stela McLachlan

    Full Text Available Red blood cell (RBC traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits-hemoglobin concentration (Hb, hematocrit (Hct, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, mean corpuscular volume (MCV and red blood cell count (RCC-in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others, 6q23.2 (with HBS1L among others, 6q23.3 (contains no genes, 9q34.3 (only ABO gene and 22q13.1 (with TMPRSS6 among others, replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.

  7. Genetic analysis of rare disorders

    DEFF Research Database (Denmark)

    van den Berg, Stéphanie M; von Bornemann Hjelmborg, Jacob

    2012-01-01

    Twin concordance rates provide insight into the possibility of a genetic background for a disease. These concordance rates are usually estimated within a frequentistic framework. Here we take a Bayesian approach. For rare diseases, estimation methods based on asymptotic theory cannot be applied due....... The Bayesian method is able to include prior information on both concordance rates and prevalence rates at the same time and is illustrated using twin data on cleft lip and rheumatoid arthritis....

  8. Integrated analysis of genetic data with R

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2006-01-01

    Full Text Available Abstract Genetic data are now widely available. There is, however, an apparent lack of concerted effort to produce software systems for statistical analysis of genetic data compared with other fields of statistics. It is often a tremendous task for end-users to tailor them for particular data, especially when genetic data are analysed in conjunction with a large number of covariates. Here, R http://www.r-project.org, a free, flexible and platform-independent environment for statistical modelling and graphics is explored as an integrated system for genetic data analysis. An overview of some packages currently available for analysis of genetic data is given. This is followed by examples of package development and practical applications. With clear advantages in data management, graphics, statistical analysis, programming, internet capability and use of available codes, it is a feasible, although challenging, task to develop it into an integrated platform for genetic analysis; this will require the joint efforts of many researchers.

  9. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    International Nuclear Information System (INIS)

    Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H.; Herrmann, Andreas

    2016-01-01

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA_1 D130E, HA_2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  10. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

    2016-05-15

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  11. Genetic analysis of Mexican Criollo cattle populations.

    Science.gov (United States)

    Ulloa-Arvizu, R; Gayosso-Vázquez, A; Ramos-Kuri, M; Estrada, F J; Montaño, M; Alonso, R A

    2008-10-01

    The objective of this study was to evaluate the genetic structure of Mexican Criollo cattle populations using microsatellite genetic markers. DNA samples were collected from 168 animals from four Mexican Criollo cattle populations, geographically isolated in remote areas of Sierra Madre Occidental (West Highlands). Also were included samples from two breeds with Iberian origin: the fighting bull (n = 24) and the milking central American Criollo (n = 24) and one Asiatic breed: Guzerat (n = 32). Genetic analysis consisted of the estimation of the genetic diversity in each population by the allele number and the average expected heterozygosity found in nine microsatellite loci. Furthermore, genetic relationships among the populations were defined by their genetic distances. Our data shows that Mexican cattle populations have a relatively high level of genetic diversity based either on the mean number of alleles (10.2-13.6) and on the expected heterozygosity (0.71-0.85). The degree of observed homozygosity within the Criollo populations was remarkable and probably caused by inbreeding (reduced effective population size) possibly due to reproductive structure within populations. Our data shows that considerable genetic differentiation has been occurred among the Criollo cattle populations in different regions of Mexico.

  12. Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.

    Science.gov (United States)

    Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B

    2018-08-27

    Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants such as plasticizers) are consistent across samples, and can be removed by background subtraction from blank injections. On the contrary, it is shown here that chemical contaminants may vary in abundance across each injection, potentially leading to their misidentification as relevant sample components. With this metabolomics study, we demonstrate the effectiveness of hierarchical cluster analysis (HCA) of replicate injections (technical replicates) as a methodology to identify chemical interferents and reduce their contaminating contribution to metabolomics models. Pools of metabolites with varying complexity were prepared from the botanical Angelica keiskei Koidzumi and spiked with known metabolites. Each set of pools was analyzed in triplicate and at multiple concentrations using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Before filtering, HCA failed to cluster replicates in the data sets. To identify contaminant peaks, we developed a filtering process that evaluated the relative peak area variance of each variable within triplicate injections. These interferent peaks were found across all samples, but did not show consistent peak area from injection to injection, even when evaluating the same chemical sample. This filtering process identified 128 ions that appear to originate from the UPLC-MS system. Data sets collected for a high number of pools with comparatively simple chemical composition were highly influenced by these chemical interferents, as were samples that were analyzed at a low concentration. When chemical interferent masses were removed, technical replicates clustered in

  13. Emergence of cooperation in phenotypically heterogeneous populations: a replicator dynamics analysis

    International Nuclear Information System (INIS)

    Barreira da Silva Rocha, A; Escobedo, R; Laruelle, A

    2015-01-01

    The emergence of cooperation is analyzed in heterogeneous populations where two kinds of individuals exist according to their phenotypic appearance. Phenotype recognition is assumed for all individuals: individuals are able to identify the type of every other individual, but fail to recognize their own type. Individuals thus behave under partial information conditions. The interactions between individuals are described by the snowdrift game, where individuals can either cooperate or defect. The evolution of such populations is studied in the framework of evolutionary game theory by means of the replicator dynamics. Overlapping generations are considered, so the replicator equations are formulated in discrete-time form. The stability analysis of the dynamical system is carried out and a detailed description of the behavior of trajectories starting from the interior of the state-space is given. We find that the four monomorphic states are unstable and that a polymorphic state exists which is a global attractor for non-degenerate initial states of the population. The result for the discrete-time replicator coincides with the one of the continuous case. (paper)

  14. Support, shape and number of replicate samples for tree foliage analysis.

    Science.gov (United States)

    Luyssaert, Sebastiaan; Mertens, Jan; Raitio, Hannu

    2003-06-01

    Many fundamental features of a sampling program are determined by the heterogeneity of the object under study and the settings for the error (alpha), the power (beta), the effect size (ES), the number of replicate samples, and sample support, which is a feature that is often overlooked. The number of replicates, alpha, beta, ES, and sample support are interconnected. The effect of the sample support and its shape on the required number of replicate samples was investigated by means of a resampling method. The method was applied to a simulated distribution of Cd in the crown of a Salix fragilis L. tree. Increasing the dimensions of the sample support results in a decrease in the variance of the element concentration under study. Analysis of the variance is often the foundation of statistical tests, therefore, valid statistical testing requires the use of a fixed sample support during the experiment. This requirement might be difficult to meet in time-series analyses and long-term monitoring programs. Sample supports have their largest dimension in the direction with the largest heterogeneity, i.e. the direction representing the crown height, and this will give more accurate results than supports with other shapes. Taking the relationships between the sample support and the variance of the element concentrations in tree crowns into account provides guidelines for sampling efficiency in terms of precision and costs. In terms of time, the optimal support to test whether the average Cd concentration of the crown exceeds a threshold value is 0.405 m3 (alpha = 0.05, beta = 0.20, ES = 1.0 mg kg(-1) dry mass). The average weight of this support is 23 g dry mass, and 11 replicate samples need to be taken. It should be noted that in this case the optimal support applies to Cd under conditions similar to those of the simulation, but not necessarily all the examinations for this tree species, element, and hypothesis test.

  15. Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication.

    Science.gov (United States)

    Pudupakam, R S; Kenney, Scott P; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A; Leroith, Tanya; Pierson, F William; Meng, Xiang-Jin

    2011-10-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.

  16. Genetic divergence analysis in pumpkin

    International Nuclear Information System (INIS)

    Quamruzzaman, A.M.; Moniruzzaman, M.

    2013-01-01

    Genetic divergence among 18 punpkin genotypes was estimated using Mahalanohis's 1) statistic. Altogether lour clusters were formed where cluster I contained the highest number of genotypes (8) and cluster II contained the lowest (I). The highest intra-cluster distance was observed h.ir cluster I (0.83 I) and the lowest for clustcr IV (0.65 I). The highest inter-cluster distance was observed between cluster I and 11(24.346). Cluster II recorded the highest mean for fruit number/plant, TSS, fruit yield and niinitnuiii III cavity length and cavity diameter. Cluster III had the second highest mean for fruit diameter, fruit number/plant, individual unit weight, fruit yield and the fewest number of days to 1st Female flowering, earliness being a desirable trait. These crosses may produce new recombinants with desirable traits. (author)

  17. DNA Damage Response Resulting from Replication Stress Induced by Synchronization of Cells by Inhibitors of DNA Replication: Analysis by Flow Cytometry.

    Science.gov (United States)

    Halicka, Dorota; Zhao, Hong; Li, Jiangwei; Garcia, Jorge; Podhorecka, Monika; Darzynkiewicz, Zbigniew

    2017-01-01

    Cell synchronization is often achieved by transient inhibition of DNA replication. When cultured in the presence of such inhibitors as hydroxyurea, aphidicolin or excess of thymidine the cells that become arrested at the entrance to S-phase upon release from the block initiate progression through S then G 2 and M. However, exposure to these inhibitors at concentrations commonly used to synchronize cells leads to activation of ATR and ATM protein kinases as well as phosphorylation of Ser139 of histone H2AX. This observation of DNA damage signaling implies that synchronization of cells by these inhibitors is inducing replication stress. Thus, a caution should be exercised while interpreting data obtained with use of cells synchronized this way since they do not represent unperturbed cell populations in a natural metabolic state. This chapter critically outlines virtues and vices of most cell synchronization methods. It also presents the protocol describing an assessment of phosphorylation of Ser139 on H2AX and activation of ATM in cells treated with aphidicolin, as a demonstrative of one of several DNA replication inhibitors that are being used for cell synchronization. Phosphorylation of Ser139H2AX and Ser1981ATM in individual cells is detected immunocytochemically with phospho-specific Abs and intensity of immunofluorescence is measured by flow cytometry. Concurrent measurement of cellular DNA content followed by multiparameter analysis allows one to correlate the extent of phosphorylation of these proteins in response to aphidicolin with the cell cycle phase.

  18. A large replication study and meta-analysis in European samples provides further support for association of AHI1 markers with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, Andrés; Giegling, Ina; Cichon, Sven

    2010-01-01

    The Abelson helper integration site 1 (AHI1) gene locus on chromosome 6q23 is among a group of candidate loci for schizophrenia susceptibility that were initially identified by linkage followed by linkage disequilibrium mapping, and subsequent replication of the association in an independent sample....... Here, we present results of a replication study of AHI1 locus markers, previously implicated in schizophrenia, in a large European sample (in total 3907 affected and 7429 controls). Furthermore, we perform a meta-analysis of the implicated markers in 4496 affected and 18,920 controls. Both...... as the neighbouring phosphodiesterase 7B (PDE7B)-may be considered candidates for involvement in the genetic aetiology of schizophrenia....

  19. Rapid Genetic Analysis in Congenital Hyperinsulinism

    DEFF Research Database (Denmark)

    Christesen, Henrik Thybo; Brusgaard, Klaus; Alm, Jan

    2007-01-01

    BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated...... with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation....... METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease...

  20. DNA replication and cancer

    DEFF Research Database (Denmark)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-01-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

  1. An integrated system for genetic analysis

    Directory of Open Access Journals (Sweden)

    Duan Xiao

    2006-04-01

    Full Text Available Abstract Background Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use. Description We have developed an Integrated Genotyping System (IGS to meet this need. IGS securely stores, edits and analyses genotype and phenotype data. It stores information about DNA samples, plates, primers, markers and genotypes generated by a genotyping laboratory. Data are structured so that statistical genetic analysis of both case-control and pedigree data is straightforward. Conclusion IGS can model complex phenotypes and contain genotypes from whole genome association studies. The database makes it possible to integrate genetic analysis with data curation. The IGS web site http://bioinformatics.well.ox.ac.uk/project-igs.shtml contains further information.

  2. Event History Analysis in Quantitative Genetics

    DEFF Research Database (Denmark)

    Maia, Rafael Pimentel

    Event history analysis is a clas of statistical methods specially designed to analyze time-to-event characteristics, e.g. the time until death. The aim of the thesis was to present adequate multivariate versions of mixed survival models that properly represent the genetic aspects related to a given...

  3. Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change.

    Directory of Open Access Journals (Sweden)

    Deanna N Edwards

    Full Text Available Recent research indicates that hundreds of thousands of G-rich sequences within the human genome have the potential to form secondary structures known as G-quadruplexes. Telomeric regions, consisting of long arrays of TTAGGG/AATCCC repeats, are among the most likely areas in which these structures might form. Since G-quadruplexes assemble from certain G-rich single-stranded sequences, they might arise when duplex DNA is unwound such as during replication. Coincidentally, these bulky structures when present in the DNA template might also hinder the action of DNA polymerases. In this study, single-stranded telomeric templates with the potential to form G-quadruplexes were examined for their effects on a variety of replicative and translesion DNA polymerases from humans and lower organisms. Our results demonstrate that single-stranded templates containing four telomeric GGG runs fold into intramolecular G-quadruplex structures. These intramolecular G quadruplexes are somewhat dynamic in nature and stabilized by increasing KCl concentrations and decreasing temperatures. Furthermore, the presence of these intramolecular G-quadruplexes in the template dramatically inhibits DNA synthesis by various DNA polymerases, including the human polymerase δ employed during lagging strand replication of G-rich telomeric strands and several human translesion DNA polymerases potentially recruited to sites of replication blockage. Notably, misincorporation of nucleotides is observed when certain translesion polymerases are employed on substrates containing intramolecular G-quadruplexes, as is extension of the resulting mismatched base pairs upon dynamic unfolding of this secondary structure. These findings reveal the potential for blockage of DNA replication and genetic changes related to sequences capable of forming intramolecular G-quadruplexes.

  4. An Analysis of Database Replication Technologies with Regard to Deep Space Network Application Requirements

    Science.gov (United States)

    Connell, Andrea M.

    2011-01-01

    The Deep Space Network (DSN) has three communication facilities which handle telemetry, commands, and other data relating to spacecraft missions. The network requires these three sites to share data with each other and with the Jet Propulsion Laboratory for processing and distribution. Many database management systems have replication capabilities built in, which means that data updates made at one location will be automatically propagated to other locations. This project examines multiple replication solutions, looking for stability, automation, flexibility, performance, and cost. After comparing these features, Oracle Streams is chosen for closer analysis. Two Streams environments are configured - one with a Master/Slave architecture, in which a single server is the source for all data updates, and the second with a Multi-Master architecture, in which updates originating from any of the servers will be propagated to all of the others. These environments are tested for data type support, conflict resolution, performance, changes to the data structure, and behavior during and after network or server outages. Through this experimentation, it is determined which requirements of the DSN can be met by Oracle Streams and which cannot.

  5. Statistical Analysis of Microarray Data with Replicated Spots: A Case Study with Synechococcus WH8102

    Directory of Open Access Journals (Sweden)

    E. V. Thomas

    2009-01-01

    Full Text Available Until recently microarray experiments often involved relatively few arrays with only a single representation of each gene on each array. A complete genome microarray with multiple spots per gene (spread out spatially across the array was developed in order to compare the gene expression of a marine cyanobacterium and a knockout mutant strain in a defined artificial seawater medium. Statistical methods were developed for analysis in the special situation of this case study where there is gene replication within an array and where relatively few arrays are used, which can be the case with current array technology. Due in part to the replication within an array, it was possible to detect very small changes in the levels of expression between the wild type and mutant strains. One interesting biological outcome of this experiment is the indication of the extent to which the phosphorus regulatory system of this cyanobacterium affects the expression of multiple genes beyond those strictly involved in phosphorus acquisition.

  6. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Peila Chen

    2010-05-01

    Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.

  7. Analysis of JC virus DNA replication using a quantitative and high-throughput assay

    International Nuclear Information System (INIS)

    Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.

    2014-01-01

    Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication

  8. Analysis of JC virus DNA replication using a quantitative and high-throughput assay

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Gagnon, David [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Gjoerup, Ole [Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111 (United States); Archambault, Jacques [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Bullock, Peter A., E-mail: Peter.Bullock@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States)

    2014-11-15

    Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication.

  9. STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study.

    Science.gov (United States)

    Diaz-Gallo, Lina Marcela; Palomino-Morales, Rogelio J; Gómez-García, María; Cardeña, Carlos; Rodrigo, Luis; Nieto, Antonio; Alcain, Guillermo; Cueto, Ignacio; López-Nevot, Miguel A; Martin, Javier

    2010-05-01

    Recently, the signal transducer and activator of transcription 4 (STAT4) gene has been associated with multiple autoimmune diseases. Interestingly, a recent work showed that the T allele of the rs7574865 STAT4 SNP was associated with inflammatory bowel disease (IBD) in a Spanish population. The aim of the present study was to reevaluate the role of the STAT4 rs7574865 polymorphism on IBD. The present case-control study included 498 Crohn's disease (CD) patients, 402 ulcerative colitis (UC) patients, and 1296 healthy matched controls. Genotyping was performed using a PCR system with a pre-developed TaqMan allelic discrimination assay for the rs7574865 STAT4 SNP. Moreover, a meta-analysis was performed with the previous work in a Spanish population and the current study, including a final sample size of 1574 IBD patients (820 with CD and 754 with UC) and 2012 healthy controls. No evidence of association was found for the current case-control study (CD: p = 0.23, OR = 0.9, 95% CI = 0.75-1.1; UC: p = 0.17, OR = 1.14, 95% CI = 0.95-1.38). However, the meta-analysis showed that the STAT4 rs7574865 T allele was significantly associated with susceptibility to UC (p = 0.012 pooled; OR = 1.20, 95% CI = 1.04-1.39) but not CD (p = 0.71 pooled; OR = 0.93, 95% CI = 0.65-1.34). Our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for UC but not CD in the Spanish population. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  10. Methods for genetic linkage analysis using trisomies.

    OpenAIRE

    Feingold, E; Lamb, N E; Sherman, S L

    1995-01-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of "susceptibility" ...

  11. Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

    Full Text Available Abstract Background It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO. Results We first estimated all pairwise additive and nonadditive genetic effects using the multifactor dimensionality reduction (MDR method that makes few assumptions about the underlying genetic model. Statistical significance was evaluated using permutation testing in two genome-wide association studies of ALS. The detection data consisted of 276 subjects with ALS and 271 healthy controls while the replication data consisted of 221 subjects with ALS and 211 healthy controls. Both studies included genotypes from approximately 550,000 single-nucleotide polymorphisms (SNPs. Each SNP was mapped to a gene if it was within 500 kb of the start or end. Each SNP was assigned a p-value based on its strongest joint effect with the other SNPs. We then used the Exploratory Visual Analysis (EVA method and software to assign a p-value to each gene based on the overabundance of significant SNPs at the α = 0.05 level in the gene. We also used EVA to assign p-values to each GO group based on the overabundance of significant genes at the α = 0.05 level. A GO category was determined to replicate if that category was significant at the α = 0.05 level in both studies. We found two GO categories that replicated in both studies. The first, ‘Regulation of Cellular Component Organization and Biogenesis’, a GO Biological Process, had p-values of 0.010 and 0.014 in the detection and replication studies, respectively. The second, ‘Actin Cytoskeleton’, a GO Cellular Component, had p-values of 0.040 and 0.046 in the detection and replication studies, respectively. Conclusions Pathway

  12. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

    Science.gov (United States)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Analysis of genetic polymorphism and genetic distance among four ...

    African Journals Online (AJOL)

    use

    2011-11-21

    Nov 21, 2011 ... The genomes of 4 sheep populations {Yuanqu white Tan sheep (YWT), Baozhongchang white Tan sheep. (BWT), black Tan sheep (BT) and small-tailed Han sheep (Han)} were screened using 10 microsatellite. DNA markers to estimate the genetic diversities and genetic distances among these ...

  14. Distributional Replication

    OpenAIRE

    Beare, Brendan K.

    2009-01-01

    Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...

  15. Reliability analysis of a replication with limited number of journaling files

    International Nuclear Information System (INIS)

    Kimura, Mitsutaka; Imaizumi, Mitsuhiro; Nakagawa, Toshio

    2013-01-01

    Recently, replication mechanisms using journaling files have been widely used for the server systems. We have already discussed the model of asynchronous replication system using journaling files [8]. This paper formulates a stochastic model of a server system with replication considering the number of transmitting journaling files. The server updates the storage database and transmits the journaling file when a client requests the data update. The server transmits the database content to a backup site either at a constant time or after a constant number of transmitting journaling files. We derive the expected number of the replication and of transmitting journaling files. Further, we calculate the expected cost and discuss optimal replication interval to minimize it. Finally, numerical examples are given

  16. Determination of selenium in food matrices by replicate sample neutron activation analysis

    International Nuclear Information System (INIS)

    Ventura, M.G.; Freitas, M.C.; Ventura, M.G.; Pacheco, A.M.G.

    2009-01-01

    The replicate sample instrumental neutron activation method was optimized and used for the determination of selenium in foodstuffs. The method was reliable, yielding accurate results. Lower detections limits were obtained after each successive irradiation. Different irradiation conditions were used depending on the type of sample. For samples with higher selenium contents (meat, fish, eggs), the measured selenium in the first replicate is in all cases larger than the detection limit, but a better accuracy was obtained with a larger number of replicates (2-3 replicates). For samples with extremely low selenium contents (vegetable samples), at least seven replicates were necessary to obtain a concentration value two times larger than the detection limit. (author)

  17. A Genetic Analysis of Mortality in Pigs

    DEFF Research Database (Denmark)

    Varona, Luis; Sorensen, Daniel

    2010-01-01

    to investigate whether there is support for genetic variation for mortality and to study the quality of fit and predictive properties of the various models. In both breeds, the model that provided the best fit to the data was the standard binomial hierarchical model. The model that performed best in terms......An analysis of mortality is undertaken in two breeds of pigs: Danish Landrace and Yorkshire. Zero-inflated and standard versions of hierarchical Poisson, binomial, and negative binomial Bayesian models were fitted using Markov chain Monte Carlo (MCMC). The objectives of the study were...... of the ability to predict the distribution of stillbirths was the hierarchical zero-inflated negative binomial model. The best fit of the binomial hierarchical model and of the zero-inflated hierarchical negative binomial model was obtained when genetic variation was included as a parameter. For the hierarchical...

  18. An analysis of the genetic diversity and genetic structure of ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-26

    Dec 26, 2011 ... relief, diuresis, blood pressure and lipid metabolism. (Kawasaki et al., 2000). ... Habitat. Longitude(N),. Latitude(E). Population size. Sample size. LY. Luoyang, Henan ..... Compared with the high genetic diversity at the species.

  19. Analysis of JC virus DNA replication using a quantitative and high-throughput assay

    Science.gov (United States)

    Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.

    2015-01-01

    Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. PMID:25155200

  20. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  1. Population genetic analysis of ascertained SNP data

    Directory of Open Access Journals (Sweden)

    Nielsen Rasmus

    2004-03-01

    Full Text Available Abstract The large single nucleotide polymorphism (SNP typing projects have provided an invaluable data resource for human population geneticists. Almost all of the available SNP loci, however, have been identified through a SNP discovery protocol that will influence the allelic distributions in the sampled loci. Standard methods for population genetic analysis based on the available SNP data will, therefore, be biased. This paper discusses the effect of this ascertainment bias on allelic distributions and on methods for quantifying linkage disequilibrium and estimating demographic parameters. Several recently developed methods for correcting for the ascertainment bias will also be discussed.

  2. Convergence analysis of canonical genetic algorithms.

    Science.gov (United States)

    Rudolph, G

    1994-01-01

    This paper analyzes the convergence properties of the canonical genetic algorithm (CGA) with mutation, crossover and proportional reproduction applied to static optimization problems. It is proved by means of homogeneous finite Markov chain analysis that a CGA will never converge to the global optimum regardless of the initialization, crossover, operator and objective function. But variants of CGA's that always maintain the best solution in the population, either before or after selection, are shown to converge to the global optimum due to the irreducibility property of the underlying original nonconvergent CGA. These results are discussed with respect to the schema theorem.

  3. Replication Catastrophe

    DEFF Research Database (Denmark)

    Toledo, Luis; Neelsen, Kai John; Lukas, Jiri

    2017-01-01

    Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...

  4. Dissecting virus entry: Replication-independent analysis of virus binding, internalization, and penetration using minimal complementation of β-galactosidase

    NARCIS (Netherlands)

    Burkard, Christine; Bloyet, Louis Marie; Wicht, Oliver; Van Kuppeveld, Frank J.; Rottier, Peter J M; De Haan, Cornelis A M; Bosch, Berend Jan

    2014-01-01

    Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this

  5. Analysis of the temporal program of replication initiation in yeast chromosomes.

    Science.gov (United States)

    Friedman, K L; Raghuraman, M K; Fangman, W L; Brewer, B J

    1995-01-01

    The multiple origins of eukaryotic chromosomes vary in the time of their initiation during S phase. In the chromosomes of Saccharomyces cerevisiae the presence of a functional telomere causes nearby origins to delay initiation until the second half of S phase. The key feature of telomeres that causes the replication delay is the telomeric sequence (C(1-3)A/G(1-3)T) itself and not the proximity of the origin to a DNA end. A second group of late replicating origins has been found at an internal position on chromosome XIV. Four origins, spanning approximately 140 kb, initiate replication in the second half of S phase. At least two of these internal origins maintain their late replication time on circular plasmids. Each of these origins can be separated into two functional elements: those sequences that provide origin function and those that impose late activation. Because the assay for determining replication time is costly and laborious, it has not been possible to analyze in detail these 'late' elements. We report here the development of two new assays for determining replication time. The first exploits the expression of the Escherichia coli dam methylase in yeast and the characteristic period of hemimethylation that transiently follows the passage of a replication fork. The second uses quantitative hybridization to detect two-fold differences in the amount of specific restriction fragments as a function of progress through S phase. The novel aspect of this assay is the creation in vivo of a non-replicating DNA sequence by site-specific pop-out recombination. This non-replicating fragment acts as an internal control for copy number within and between samples. Both of these techniques are rapid and much less costly than the more conventional density transfer experiments that require CsCl gradients to detect replicated DNA. With these techniques it should be possible to identify the sequences responsible for late initiation, to search for other late replicating

  6. Nucleotide sequence analysis of regions of adenovirus 5 DNA containing the origins of DNA replication

    International Nuclear Information System (INIS)

    Steenbergh, P.H.

    1979-01-01

    The purpose of the investigations described is the determination of nucleotide sequences at the molecular ends of the linear adenovirus type 5 DNA. Knowledge of the primary structure at the termini of this DNA molecule is of particular interest in the study of the mechanism of replication of adenovirus DNA. The initiation- and termination sites of adenovirus DNA replication are located at the ends of the DNA molecule. (Auth.)

  7. Analysis of genetic structure and relationship among nine ...

    Indian Academy of Sciences (India)

    These results indicated that the clustering analysis using the Structure program might provide an ..... of the current genetic relations among the breeds, and con- tribute to ... sis of the genetic structure of the Canary goat populations using.

  8. Genetic analysis of Myanmar Vigna species in responses to salt ...

    African Journals Online (AJOL)

    Genetic analysis of Myanmar Vigna species in responses to salt stress at the ... of reduction was highly dependent on different genotypes and salinity levels. ... the mechanism of salt tolerance and for the provision of genetic resources for ...

  9. Analysis of genetic relationships of mulberry (Morus L.) germplasm ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... Full Length Research Paper. Analysis of genetic ... Key words: Mulberry, molecular marker, genetic diversity, SRAP. ... Europe, North and South America, and Africa, and it is cultivated ... Xingjiang autonomous region, China.

  10. A genetic epidemiological mega analysis of smoking initiation in adolescents

    NARCIS (Netherlands)

    Maes, H.H.; Prom-Wormley, E.; Eaves, L.J.; Rhee, S.H.; Hewitt, J.K.; Young, S.; Corley, R.; McGue, M.K.; Iacono, W.G.; Legrand, L.; Samek, D.; Murrelle, E.L.; Silberg, J.L.; Miles, D.; Schieken, R.M.; Beunen, G.P.; Thomis, M.; Rose, R.J.; Dick, D.M.; Boomsma, D.I.; Bartels, M.; Vink, J.M.; Lichtenstein, P.; White, V.; Kaprio, J.; Neale, M.C.

    2017-01-01

    Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural

  11. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

    This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

  12. Molecular approaches to the analysis of deformed wing virus replication and pathogenesis in the honey bee, Apis mellifera

    Directory of Open Access Journals (Sweden)

    Pettis Jeffery S

    2009-12-01

    Full Text Available Abstract Background For years, the understanding of the pathogenetic mechanisms that underlie honey bee viral diseases has been severely hindered because of the lack of a cell culture system for virus propagation. As a result, it is very imperative to develop new methods that would permit the in vitro pathogenesis study of honey bee viruses. The identification of virus replication is an important step towards the understanding of the pathogenesis process of viruses in their respective hosts. In the present study, we developed a strand-specific RT-PCR-based method for analysis of Deformed Wing Virus (DWV replication in honey bees and in honey bee parasitic mites, Varroa Destructor. Results The results shows that the method developed in our study allows reliable identification of the virus replication and solves the problem of falsely-primed cDNA amplifications that commonly exists in the current system. Using TaqMan real-time quantitative RT-PCR incorporated with biotinylated primers and magnetic beads purification step, we characterized the replication and tissue tropism of DWV infection in honey bees. We provide evidence for DWV replication in the tissues of wings, head, thorax, legs, hemolymph, and gut of honey bees and also in Varroa mites. Conclusion The strategy reported in the present study forms a model system for studying bee virus replication, pathogenesis and immunity. This study should be a significant contribution to the goal of achieving a better understanding of virus pathogenesis in honey bees and to the design of appropriate control measures for bee populations at risk to virus infections.

  13. Genetic parameters and path analysis in cowpea genotypes grown in the Cerrado/Pantanal ecotone.

    Science.gov (United States)

    Lopes, K V; Teodoro, P E; Silva, F A; Silva, M T; Fernandes, R L; Rodrigues, T C; Faria, T C; Corrêa, A M

    2017-05-18

    Estimating genetic parameters in plant breeding allows us to know the population potential for selecting and designing strategies that can maximize the achievement of superior genotypes. The objective of this study was to evaluate the genetic potential of a population of 20 cowpea genotypes by estimating genetic parameters and path analysis among the traits to guide the selection strategies. The trial was conducted in randomized block design with four replications. Its morphophysiological components, components of green grain production and dry grain yield were estimated from genetic use and correlations between the traits. Phenotypic correlations were deployed through path analysis into direct and indirect effects of morphophysiological traits and yield components on dry grain yield. There were significant differences (P < 0.01) between the genotypes for most the traits, indicating the presence of genetic variability in the population and the possibility of practicing selection. The population presents the potential for future genetic breeding studies and is highly promising for the selection of traits dry grain yield, the number of grains per pod, and hundred grains mass. A number of grains per green pod is the main determinant trait of dry grain yield that is also influenced by the cultivar cycle and that the selection for the dry grain yield can be made indirectly by selecting the green pod mass and green pod length.

  14. Analysis of classical swine fever virus RNA replication determinants using replicons

    DEFF Research Database (Denmark)

    Risager, Peter Christian; Fahnøe, Ulrik; Gullberg, Maria

    2013-01-01

    Self-replicating RNAs (replicons), with or without reporter gene sequences, derived from the genome of the Paderborn strain of classical swine fever virus (CSFV) have been produced. The full-length viral cDNA, propagated within a bacterial artificial chromosome (BAC), was modified by targeted...... recombination within E. coli. RNA transcripts were produced in vitro and introduced into cells by electroporation. The translation and replication of the replicon RNAs could be followed by the accumulation of luciferase (from Renilla reniformis or Gaussia princeps) protein expression (where appropriate......), as well as by detection of the CSFV NS3 protein production within the cells. Inclusion of the viral E2 coding region within the replicon was advantageous for the replication efficiency. Production of chimeric RNAs, substituting the NS2 and NS3 coding regions (as a unit) from the Paderborn strain...

  15. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

    2016-01-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

  16. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H

    2016-12-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.

  17. Replication protocol analysis: a method for the study of real-world design thinking

    DEFF Research Database (Denmark)

    Galle, Per; Kovacs, L. B.

    1996-01-01

    Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication......’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture...

  18. Extended local similarity analysis (eLSA) of microbial community and other time series data with replicates.

    Science.gov (United States)

    Xia, Li C; Steele, Joshua A; Cram, Jacob A; Cardon, Zoe G; Simmons, Sheri L; Vallino, Joseph J; Fuhrman, Jed A; Sun, Fengzhu

    2011-01-01

    The increasing availability of time series microbial community data from metagenomics and other molecular biological studies has enabled the analysis of large-scale microbial co-occurrence and association networks. Among the many analytical techniques available, the Local Similarity Analysis (LSA) method is unique in that it captures local and potentially time-delayed co-occurrence and association patterns in time series data that cannot otherwise be identified by ordinary correlation analysis. However LSA, as originally developed, does not consider time series data with replicates, which hinders the full exploitation of available information. With replicates, it is possible to understand the variability of local similarity (LS) score and to obtain its confidence interval. We extended our LSA technique to time series data with replicates and termed it extended LSA, or eLSA. Simulations showed the capability of eLSA to capture subinterval and time-delayed associations. We implemented the eLSA technique into an easy-to-use analytic software package. The software pipeline integrates data normalization, statistical correlation calculation, statistical significance evaluation, and association network construction steps. We applied the eLSA technique to microbial community and gene expression datasets, where unique time-dependent associations were identified. The extended LSA analysis technique was demonstrated to reveal statistically significant local and potentially time-delayed association patterns in replicated time series data beyond that of ordinary correlation analysis. These statistically significant associations can provide insights to the real dynamics of biological systems. The newly designed eLSA software efficiently streamlines the analysis and is freely available from the eLSA homepage, which can be accessed at http://meta.usc.edu/softs/lsa.

  19. Database Replication

    CERN Document Server

    Kemme, Bettina

    2010-01-01

    Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

  20. Pneumococcal Replicative State in Relation to its Adherence Capacity to A549-cell Line: A Preliminary in vitro Analysis

    Directory of Open Access Journals (Sweden)

    Mohd Desa, M. N.

    2011-01-01

    Full Text Available This study was to compare the replication capacity of pneumococcal isolates (serotypes 1, 7F, 19F and 23F with their adherence pattern to monolayer cells (A549. For standardization purposes, all isolates showed a normal growth curve in both bacteriological (THB + 0.5% yeast extract with and without 2% FBS and cell culture media (RPMI + 2% FBS. In the former media, a shorter lag phase was observed for isolate serotypes 1 and 7F in presence of serum while in the later; growth yield was lower for all isolates with stationary phase approaching OD600 of 0.01 as compared to 1.0 in bacteriological media. In the replicative analysis at different growth phases of the isolates in cell culture media, growth capacity at 3 h post-incubation was frequently twice as that at 1 h, and that at early-log phase was frequently higher than that at mid-log phase at both post-incubation times. Adherence was frequently the least at early-log phase although the isolates were in the most active state of replication to increase the number of pneumococcal cells to adhere. At mid- and late-log phases, pneumococcal adherence was frequently higher although the replication was reduced. This study marks the potential correlation between pneumococcal growth fitness and adherence capacity whereby the later may not be superior during the early growth phase.

  1. DNA markers reveal genetic structure and localized diversity of ...

    African Journals Online (AJOL)

    uqhdesma

    2016-10-12

    Oct 12, 2016 ... STRUCTURE analysis revealed 4 clusters of genetically ..... 10000 cycles and 50000 Markov Chain Monte Carlo (MCMC) iterations and 10 replicate runs performed for each K value to ..... WL, Lee M, Porter K (2000). Genetic ...

  2. Quantitative genetic analysis of total glucosinolate, oil and protein ...

    African Journals Online (AJOL)

    Quantitative genetic analysis of total glucosinolate, oil and protein contents in Ethiopian mustard ( Brassica carinata A. Braun) ... Seeds were analyzed using HPLC (glucosinolates), NMR (oil) and NIRS (protein). Analyses of variance, Hayman's method of diallel analysis and a mixed linear model of genetic analysis were ...

  3. Replication and meta-analysis of TMEM132D gene variants in panic disorder

    DEFF Research Database (Denmark)

    Erhardt, A; Akula, N; Schumacher, J

    2012-01-01

    (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n = 1038 cases and n = 2411 controls). This finding was paralleled...

  4. Support, shape and number of replicate samples for tree foliage analysis

    NARCIS (Netherlands)

    Luyssaert, Sebastiaan; Mertens, Jan; Raitio, Hannu

    Many fundamental features of a sampling program are determined by the heterogeneity of the object under study and the settings for the error (α), the power (β), the effect size (ES), the number of replicate samples, and sample support, which is a feature that is often overlooked. The number of

  5. Gamma-irradiated scrub typhus immunogens: analysis for residual replicating rickettsiae

    International Nuclear Information System (INIS)

    Eisenberg, G.H. Jr.; Osterman, J.V.; Stephenson, E.H.

    1980-01-01

    Scrub thyphus immunogens that received inadequate gamma radiation contained residual, viable rickettsiae. The presence of these organisms in the host was masked by the rapid immune response elicited by the large number of inactivated rickettsiae. Transfer of homogenized spleen cells from immunized mice to normal syngeneic recipients provided a sensitive technique for the detection of these viable, replicating organisms

  6. Personal and Interpersonal Motivation for Group Projects: Replications of an Attributional Analysis

    Science.gov (United States)

    Peterson, Sarah E.; Schreiber, James B.

    2012-01-01

    We report the results of two replication studies using attribution theory to analyze personal and interpersonal motivation for collaborative projects. Undergraduate students responded to questionnaires containing hypothetical vignettes depicting success or failure outcomes due to ability or effort for dyads working on a group project. Dependent…

  7. Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

    Directory of Open Access Journals (Sweden)

    Celedón Juan C

    2011-02-01

    Full Text Available Abstract Background Prior studies suggest a role for a variant (rs5743836 in the promoter of toll-like receptor 9 (TLR9 in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts. Methods rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity. Results Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant. Conclusion Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

  8. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    DEFF Research Database (Denmark)

    Syed, Salahuddin; Madsen, Claus Desler; Rasmussen, Lene J.

    2016-01-01

    hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5...

  9. GENETIC ANALYSIS OF ABSCISIC ACID BIOSYNTHESIS

    Energy Technology Data Exchange (ETDEWEB)

    MCCARTY D R

    2012-01-10

    The carotenoid cleavage dioxygenases (CCD) catalyze synthesis of a variety of apo-carotenoid secondary metabolites in plants, animals and bacteria. In plants, the reaction catalyzed by the 11, 12, 9-cis-epoxy carotenoid dioxygenase (NCED) is the first committed and key regulated step in synthesis of the plant hormone, abscisic acid (ABA). ABA is a key regulator of plant stress responses and has critical functions in normal root and seed development. The molecular mechanisms responsible for developmental control of ABA synthesis in plant tissues are poorly understood. Five of the nine CCD genes present in the Arabidopsis genome encode NCED's involved in control of ABA synthesis in the plant. This project is focused on functional analysis of these five AtNCED genes as a key to understanding developmental regulation of ABA synthesis and dissecting the role of ABA in plant development. For this purpose, the project developed a comprehensive set of gene knockouts in the AtNCED genes that facilitate genetic dissection of ABA synthesis. These mutants were used in combination with key molecular tools to address the following specific objectives: (1) the role of ABA synthesis in root development; (2) developmental control of ABA synthesis in seeds; (3) analysis of ATNCED over-expressers; (4) preliminary crystallography of the maize VP14 protein.

  10. Replication Studies: Vocabulary Knowledge in Relation to Memory and Analysis--An Approximate Replication of Milton's (2007) Study on Lexical Profiles and Learning Style

    Science.gov (United States)

    Booth, Paul

    2013-01-01

    This paper presents an approximate replication of Milton's (2007) study on lexical profiles and learning style. Milton investigated the assumption that more frequent words are acquired before less frequent ones. Using a vocabulary recognition test ("X-Lex") to measure vocabulary size, Milton found that L2 English group profiles show…

  11. Turning the Hands of Time Again: A Purely Confirmatory Replication Study and a Bayesian Analysis

    Directory of Open Access Journals (Sweden)

    Eric-Jan eWagenmakers

    2015-04-01

    Full Text Available In a series of four experiments, Topolinski and Sparenberg (2012; TS found support for the conjecture that clockwise movements induce psychological states of temporal progression and an orientation toward the future and novelty. Here we report the results of a preregistered replication attempt of Experiment 2 from TS. Participants turned kitchen rolls either clockwise or counterclockwise while answering items from a questionnaire assessing openness to experience. Data from 102 participants showed that the effect went slightly in the direction opposite to that predicted by TS, and a preregistered Bayes factor hypothesis test revealed that the data were 10.76 times more likely under the null hypothesis than under the alternative hypothesis. Our findings illustrate the theoretical importance and practical advantages of preregistered Bayes factor replication studies, both for psychological science and for empirical work in general.

  12. An Analysis of Weakly Consistent Replication Systems in an Active Distributed Network

    OpenAIRE

    Amit Chougule; Pravin Ghewari

    2011-01-01

    With the sudden increase in heterogeneity and distribution of data in wide-area networks, more flexible, efficient and autonomous approaches for management and data distribution are needed. In recent years, the proliferation of inter-networks and distributed applications has increased the demand for geographically-distributed replicated databases. The architecture of Bayou provides features that address the needs of database storage of world-wide applications. Key is the use of weak consisten...

  13. Visibility of news items on Twitter and Facebook: comparative analysis of the most replicated news in Europe and the Americas

    Directory of Open Access Journals (Sweden)

    Gabriela da Silva Zago

    2013-06-01

    Full Text Available This paper identifies and compares the top replicated news items on Twitter and Facebook, on news websites from Brazil, Germany, Spain, the United States and United Kingdom. The data includes 8 of the newspapers with the largest circulation in the 5 countries, totaling 40 outlets. The volume of “retweets” and “likes” was used as a metric for representing the visibility of news items. Links posted on Twitter and messages posted by newspapers on Facebook were collected for a period of two weeks during October 2012. Content analysis was carried out for the top 25 replicated messages in each social network, which uncovered significant cultural traits and editorial differences across countries, based upon the content that circulated on social networks during the period. The results confirm users’ perceptions of social networking sites, with Facebook being used largely for entertainment and recreation, and Twitter for covering political, economic, and social events.

  14. Registered Replication Report

    DEFF Research Database (Denmark)

    Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.

    2017-01-01

    and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...

  15. Genetic analysis of the Venezuelan Criollo horse.

    Science.gov (United States)

    Cothran, E G; Canelon, J L; Luis, C; Conant, E; Juras, R

    2011-10-07

    Various horse populations in the Americas have an origin in Spain; they are remnants of the first livestock introduced to the continent early in the colonial period (16th and 17th centuries). We evaluated genetic variability within the Venezuelan Criollo horse and its relationship with other horse breeds. We observed high levels of genetic diversity within the Criollo breed. Significant population differentiation was observed between all South American breeds. The Venezuelan Criollo horse showed high levels of genetic diversity, and from a conservation standpoint, there is no immediate danger of losing variation unless there is a large drop in population size.

  16. Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method

    Directory of Open Access Journals (Sweden)

    Dan Dou

    2017-07-01

    Full Text Available Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods for analyzing viral genome localization and differentiating genomes with high identity are lacking, making it difficult to investigate entry-related processes and co-examine heterogeneous RNA viral populations. Here, we present an RNA labeling approach for single-cell analysis of RNA viral replication and co-infection dynamics in situ, which uses the versatility of padlock probes. We applied this method to identify influenza A virus (IAV infections in cells and lung tissue with single-nucleotide specificity and to classify entry and replication stages by gene segment localization. Extending the classification strategy to co-infections of IAVs with single-nucleotide variations, we found that the dependence on intracellular trafficking places a time restriction on secondary co-infections necessary for genome reassortment. Altogether, these data demonstrate how RNA viral genome labeling can help dissect entry and co-infections.

  17. Personality and divorce: a genetic analysis.

    Science.gov (United States)

    Jocklin, V; McGue, M; Lykken, D T

    1996-08-01

    M. McGue and D.T. Lykken (1992) found that divorce risk was, to a substantial degree, genetically mediated; prior research has identified numerous social and psychological factors that affect divorce risk (G.C. Kitson, K.B. Barbi, & M.J. Roach, 1985). The present study attempted to link these domains by examining the extent to which genetic influences on one such psychological factor, personality, explain divorce risk heritability. A sample of adult twins from the Minnesota Twin Registry completed a marital history questionnaire and the Multidimensional Personality Questionnaire (A. Tellegen, 1982). Positive Emotionality and Negative Emotionality factors were positively related to divorce risk, whereas Constraint was negatively related. In women and men, respectively, 30% and 42% of the heritability of divorce risk consisted of genetic factors affecting personality and divorce risk correlated largely as a result of these common genetic influences.

  18. Genetic algorithms and supernovae type Ia analysis

    International Nuclear Information System (INIS)

    Bogdanos, Charalampos; Nesseris, Savvas

    2009-01-01

    We introduce genetic algorithms as a means to analyze supernovae type Ia data and extract model-independent constraints on the evolution of the Dark Energy equation of state w(z) ≡ P DE /ρ DE . Specifically, we will give a brief introduction to the genetic algorithms along with some simple examples to illustrate their advantages and finally we will apply them to the supernovae type Ia data. We find that genetic algorithms can lead to results in line with already established parametric and non-parametric reconstruction methods and could be used as a complementary way of treating SNIa data. As a non-parametric method, genetic algorithms provide a model-independent way to analyze data and can minimize bias due to premature choice of a dark energy model

  19. Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication

    Science.gov (United States)

    Pudupakam, R. S.; Kenney, Scott P.; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A.; LeRoith, Tanya; Pierson, F. William; Meng, Xiang-Jin

    2011-01-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication. PMID:21775444

  20. Analysis of genetic structure in Melia volkensii (Gurke.) populations ...

    African Journals Online (AJOL)

    Administrator

    2Farm Forestry Programme, Kenya Forestry Research Institute, P. O. Box 20412, Nairobi, Kenya. Accepted 5 ... were used to estimate genetic distances between populations and for construction of neighbour-joining phenograms. Analysis of Molecular Variance (AMOVA) indicated significant genetic differentiation between ...

  1. Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells

    Directory of Open Access Journals (Sweden)

    Marielle Cavrois

    2017-07-01

    Full Text Available To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localize to extrafollicular lymphoid regions with limited viral replication. Thus, CyTOF-based phenotyping, combined with analytical approaches to distinguish between selective infection and receptor modulation by viruses, can be used as a discovery tool.

  2. A Genetic Analysis of Crystal Growth

    DEFF Research Database (Denmark)

    Brown, Stanley; Sarikaya, Mehmet; Johnson, E.

    2000-01-01

    The regulation of crystal morphology by proteins is often observed in biology. It is a central feature in the formation of hard tissues such as bones, teeth and mollusc shells. We have developed a genetic system in the bacterium Escherichia coli to study the protein-mediated control of crystal...

  3. Analysis of the genetic diversity of four rabbit genotypes using ...

    African Journals Online (AJOL)

    Dr.Ola

    2013-05-15

    May 15, 2013 ... consumption and low cost, it has been widely utilized in genetics analysis in ... isozyme variation among the selected individuals within each rabbit genotype. ... with different embryo survival (Bolet and Theau-Clement, 1994).

  4. Genetic analysis of a consanguineous Pakistani family with Leber ...

    Indian Academy of Sciences (India)

    2014-08-01

    Aug 1, 2014 ... RESEARCH NOTE. Genetic analysis of a consanguineous Pakistani family with Leber .... representation of the deleterious mutation at genomic and protein level. ... In the last couple of years, numerous mutations in. GUCY2D ...

  5. A genetic analysis of segregation distortion revealed by molecular ...

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 90, No. ... Segregation analysis was based on 64 molecular markers, including 26 .... FHB of RIL populations was controlled by quantitative trait ... The authors acknowledge financial support by the National Basic.

  6. Analysis of genetic diversity in mango ( Mangifera indica L.) using ...

    African Journals Online (AJOL)

    Analysis of genetic diversity in mango ( Mangifera indica L.) using isozymetic polymorphism. ... All the isozymes, used in the present study showed polymorphism for mango. A total of 25 different electrophoretic ... HOW TO USE AJOL.

  7. Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

    African Journals Online (AJOL)

    Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

  8. Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders.

    Science.gov (United States)

    Pain, Oliver; Dudbridge, Frank; Cardno, Alastair G; Freeman, Daniel; Lu, Yi; Lundstrom, Sebastian; Lichtenstein, Paul; Ronald, Angelica

    2018-03-31

    This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. Single nucleotide polymorphism (SNP)-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk score (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and

  9. Analysis of in vitro replicated human hepatitis C virus (HCV for the determination of genotypes and quasispecies

    Directory of Open Access Journals (Sweden)

    Chelyapov Nickolas

    2006-09-01

    Full Text Available Abstract Isolation and self-replication of infectious HCV has been a difficult task. However, this is needed for the purposes of developing rational drugs and for the analysis of the natural virus. Our recent report of an in vitro system for the isolation of human HCV from infected patients and their replication in tissue culture addresses this challenge. At California Institute of Molecular Medicine several isolates of HCV, called CIMM-HCV, were grown for over three years in cell culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially identical. Isolates of HCV from one patient were serially transmitted into fresh cells up to eight times and the progeny viruses from each transmission were compared to each other and also to the primary isolates from the patient's serum. Some isolates were also transmitted to different cell types, while others were cultured continuously without retransmission for over three years. We noted minor sequence changes when HCV was cultured for extended periods of time. HCV in T-cells and non-committed lymphoid cells showed a few differences when compared to isolates obtained from immortalized B-cells. These viruses maintained close similarity despite repeated transmissions and passage of time. There were no subtypes or quasispecies noted in CIMM-HCV.

  10. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.

    Directory of Open Access Journals (Sweden)

    Claire L Simpson

    Full Text Available Refractive error (RE is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness and hyperopia (farsightedness, which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8, which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11 and 8q12 (minimum p value 1.82×10(-11 previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al. and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of

  11. Genetic analysis of agro-morphological traits in promising hybrids of sunflower (Helianthus annuus L.

    Directory of Open Access Journals (Sweden)

    Maryam GOLABADI

    2015-11-01

    Full Text Available The main objective underlying sunflower breeding programs is to develop high-yielding productive F1 hybrid cultivars. This study was conducted to investigate the genetic control of some agro-morphological traits of new sunflower F1 hybrids. For this purpose, fourteen inbred lines of sunflower were crossed with three male sterile inbred lines. Their hybrids (14 hybrids were then evaluated against three control cultivars. The data thus obtained were analyzed using the nested model (North Carolina Design І as a completely randomized block design (CRBD with four replications. Analysis of variance showed that the hybrids were significantly different in all the traits studied, except for head and stem diameters. From among the hybrids evaluated, Cms19 × Rn1-81 was found to have the highest seed yield and oil content. Cluster analysis classified the hybrids into four different groups. Genetic analysis showed that days to maturity, seed weight, and oil content (% were under the additive gene action. Breeding strategies based on selection could be suggested for the improvement of these traits. Head angle, head diameter, seed yield, and oil yield were under the dominance gene action; breeding based on hybridization methods is, therefore, proposed for these traits. Finally, both additive and dominance gene actions were observed to play important roles in the genetic control of plant height and stem diameter.

  12. Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes

    Science.gov (United States)

    Multhaup, Michael L.; Seldin, Marcus; Jaffe, Andrew E.; Lei, Xia; Kirchner, Henriette; Mondal, Prosenjit; Li, Yuanyuan; Rodriguez, Varenka; Drong, Alexander; Hussain, Mehboob; Lindgren, Cecilia; McCarthy, Mark; Näslund, Erik; Zierath, Juleen R.; Wong, G. William; Feinberg, Andrew P.

    2015-01-01

    SUMMARY Using a functional approach to investigate the epigenetics of Type 2 Diabetes (T2D), we combine three lines of evidence – diet-induced epigenetic dysregulation in mouse, epigenetic conservation in humans, and T2D clinical risk evidence – to identify genes implicated in T2D pathogenesis through epigenetic mechanisms related to obesity. Beginning with dietary manipulation of genetically homogeneous mice, we identify differentially DNA-methylated genomic regions. We then replicate these results in adipose samples from lean and obese patients pre- and post-Roux-en-Y gastric bypass, identifying regions where both the location and direction of methylation change is conserved. These regions overlap with 27 genetic T2D risk loci, only one of which was deemed significant by GWAS alone. Functional analysis of genes associated with these regions revealed four genes with roles in insulin resistance, demonstrating the potential general utility of this approach for complementing conventional human genetic studies by integrating cross-species epigenomics and clinical genetic risk. PMID:25565211

  13. Genetic analysis of sunflower chlorophyll mutants

    International Nuclear Information System (INIS)

    Mashkina, E.V.; Guskov, E.P.

    2001-01-01

    The method of getting the chlorophyll mutations in sunflower was developed by Y.D. Beletskii in 1969 with the use of N-nitroso-N-methylurea (NMH). Certain concentrations of NMH are known to induce plastid mutations in growing seeds, and their yield depends on the duration of the exposure. The given work presented studies on the influence of rifampicin (R) and 2,4-dinitrophenol (DNP) on the genetic activity NMH, as an inductor of plastid and nuclear mutations

  14. Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations

    Science.gov (United States)

    Cho, Eun Young; Jang, Yangsoo; Shin, Eun Soon; Jang, Hye Yoon; Yoo, Yeon-Kyeong; Kim, Sook; Jang, Ji Hyun; Lee, Ji Yeon; Yun, Min Hye; Park, Min Young; Chae, Jey Sook; Lim, Jin Woo; Shin, Dong Jik; Park, Sungha; Lee, Jong Ho; Han, Bok Ghee; Rae, Kim Hyung; Cardon, Lon R; Morris, Andrew P; Lee, Jong Eun; Clarke, Geraldine M

    2010-01-01

    Background Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. Methods The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. Results The association previously observed on chromosome 9p21 was independently replicated (p=3.08e–07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. Conclusion A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors. PMID:27325954

  15. Evolution of Replication Machines

    Science.gov (United States)

    Yao, Nina Y.; O'Donnell, Mike E.

    2016-01-01

    The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

  16. Mechanisms of bacterial DNA replication restart

    Science.gov (United States)

    Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

    2018-01-01

    Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

  17. Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

    Science.gov (United States)

    Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

    2014-01-01

    The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers. PMID:25206325

  18. Multivariate Survival Mixed Models for Genetic Analysis of Longevity Traits

    DEFF Research Database (Denmark)

    Pimentel Maia, Rafael; Madsen, Per; Labouriau, Rodrigo

    2014-01-01

    A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented co...... applications. The methods presented are implemented in such a way that large and complex quantitative genetic data can be analyzed......A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented...... concentrates on longevity studies. The framework presented allows to combine models based on continuous time with models based on discrete time in a joint analysis. The continuous time models are approximations of the frailty model in which the hazard function will be assumed to be piece-wise constant...

  19. Multivariate Survival Mixed Models for Genetic Analysis of Longevity Traits

    DEFF Research Database (Denmark)

    Pimentel Maia, Rafael; Madsen, Per; Labouriau, Rodrigo

    2013-01-01

    A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented co...... applications. The methods presented are implemented in such a way that large and complex quantitative genetic data can be analyzed......A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented...... concentrates on longevity studies. The framework presented allows to combine models based on continuous time with models based on discrete time in a joint analysis. The continuous time models are approximations of the frailty model in which the hazard function will be assumed to be piece-wise constant...

  20. Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

    Science.gov (United States)

    2016-01-01

    Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID:27654267

  1. Genetic analysis of variation in human meiotic recombination.

    Directory of Open Access Journals (Sweden)

    Reshmi Chowdhury

    2009-09-01

    Full Text Available The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31 were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1, results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss.

  2. Evolution of complexity in RNA-like replicator systems

    Directory of Open Access Journals (Sweden)

    Hogeweg Paulien

    2008-03-01

    Full Text Available Abstract Background The evolution of complexity is among the most important questions in biology. The evolution of complexity is often observed as the increase of genetic information or that of the organizational complexity of a system. It is well recognized that the formation of biological organization – be it of molecules or ecosystems – is ultimately instructed by the genetic information, whereas it is also true that the genetic information is functional only in the context of the organization. Therefore, to obtain a more complete picture of the evolution of complexity, we must study the evolution of both information and organization. Results Here we investigate the evolution of complexity in a simulated RNA-like replicator system. The simplicity of the system allows us to explicitly model the genotype-phenotype-interaction mapping of individual replicators, whereby we avoid preconceiving the functionality of genotypes (information or the ecological organization of replicators in the model. In particular, the model assumes that interactions among replicators – to replicate or to be replicated – depend on their secondary structures and base-pair matching. The results showed that a population of replicators, originally consisting of one genotype, evolves to form a complex ecosystem of up to four species. During this diversification, the species evolve through acquiring unique genotypes with distinct ecological functionality. The analysis of this diversification reveals that parasitic replicators, which have been thought to destabilize the replicator's diversity, actually promote the evolution of diversity through generating a novel "niche" for catalytic replicators. This also makes the current replicator system extremely stable upon the evolution of parasites. The results also show that the stability of the system crucially depends on the spatial pattern formation of replicators. Finally, the evolutionary dynamics is shown to

  3. Polyglot programming in applications used for genetic data analysis.

    Science.gov (United States)

    Nowak, Robert M

    2014-01-01

    Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development.

  4. COMPARITIVE GENETIC DIVERSITY ANALYSIS OF OAT (Avena ...

    African Journals Online (AJOL)

    knsccf

    protein and 30 to 35% dry matter. ... environment interaction, hence not much dependable but ... Principal coordinate (3D) analysis was .... Relationships among 20 genotypes of oat visualized by principal component analysis (PCoA) of rainfed ...

  5. The logic of DNA replication in double-stranded DNA viruses: insights from global analysis of viral genomes.

    Science.gov (United States)

    Kazlauskas, Darius; Krupovic, Mart; Venclovas, Česlovas

    2016-06-02

    Genomic DNA replication is a complex process that involves multiple proteins. Cellular DNA replication systems are broadly classified into only two types, bacterial and archaeo-eukaryotic. In contrast, double-stranded (ds) DNA viruses feature a much broader diversity of DNA replication machineries. Viruses differ greatly in both completeness and composition of their sets of DNA replication proteins. In this study, we explored whether there are common patterns underlying this extreme diversity. We identified and analyzed all major functional groups of DNA replication proteins in all available proteomes of dsDNA viruses. Our results show that some proteins are common to viruses infecting all domains of life and likely represent components of the ancestral core set. These include B-family polymerases, SF3 helicases, archaeo-eukaryotic primases, clamps and clamp loaders of the archaeo-eukaryotic type, RNase H and ATP-dependent DNA ligases. We also discovered a clear correlation between genome size and self-sufficiency of viral DNA replication, the unanticipated dominance of replicative helicases and pervasive functional associations among certain groups of DNA replication proteins. Altogether, our results provide a comprehensive view on the diversity and evolution of replication systems in the DNA virome and uncover fundamental principles underlying the orchestration of viral DNA replication. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Parameter determination for quantitative PIXE analysis using genetic algorithms

    International Nuclear Information System (INIS)

    Aspiazu, J.; Belmont-Moreno, E.

    1996-01-01

    For biological and environmental samples, PIXE technique is in particular advantage for elemental analysis, but the quantitative analysis implies accomplishing complex calculations that require the knowledge of more than a dozen parameters. Using a genetic algorithm, the authors give here an account of the procedure to obtain the best values for the parameters necessary to fit the efficiency for a X-ray detector. The values for some variables involved in quantitative PIXE analysis, were manipulated in a similar way as the genetic information is treated in a biological process. The authors carried out the algorithm until they reproduce, within the confidence interval, the elemental concentrations corresponding to a reference material

  7. Genetic Diversity of Rose germplasm based on RAPD analysis

    African Journals Online (AJOL)

    AHSAN IQBAL

    2012-06-12

    Jun 12, 2012 ... identification and analysis of genetic variation within a collection of 4 species and 30 accessions of rose using RAPD analysis technique. The results showed the molecular distinctions among the ... that range in colour from white and yellow to many shades of pink and red have been developed. Since.

  8. Genetic data analysis for plant and animal breeding

    Science.gov (United States)

    This book is an advanced textbook covering the application of quantitative genetics theory to analysis of actual data (both trait and DNA marker information) for breeding populations of crops, trees, and animals. Chapter 1 is an introduction to basic software used for trait data analysis. Chapter 2 ...

  9. Bioinformatics analysis and genetic diversity of the poliovirus.

    Science.gov (United States)

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Wang, Shujing; Xu, Ruixue

    2014-12-01

    Poliomyelitis, a disease which can manifest as muscle paralysis, is caused by the poliovirus, which is a human enterovirus and member of the family Picornaviridae that usually transmits by the faecal-oral route. The viruses of the OPV (oral poliovirus attenuated-live vaccine) strains can mutate in the human intestine during replication and some of these mutations can lead to the recovery of serious neurovirulence. Informatics research of the poliovirus genome can be used to explain further the characteristics of this virus. In this study, sequences from 100 poliovirus isolates were acquired from GenBank. To determine the evolutionary relationship between the strains, we compared and analysed the sequences of the complete poliovirus genome and the VP1 region. The reconstructed phylogenetic trees for the complete sequences and the VP1 sequences were both divided into two branches, indicating that the genetic relationships of the whole poliovirus genome and the VP1 sequences are very similar. This branching indicates that the virulence and pathogenicity of poliomyelitis may be associated with the VP1 region. Sequence alignment of the VP1 region revealed numerous mutation sites in which mutation rates of >30 % were detected. In a group of strains recorded in the USA, mutation sites and mutation types were the same and this may be associated with their distribution in the evolutionary tree and their genetic relationship. In conclusion, the genetic evolutionary relationships of poliovirus isolate sequences are determined to a great extent by the VP1 protein, and poliovirus strains located on the same branch of the phylogenetic tree contain the same mutation spots and mutation types. Hence, the genetic characteristics of the VP1 region in the poliovirus genome should be analysed to identify the transmission route of poliovirus and provide the basis of viral immunity development. © 2014 The Authors.

  10. Mutant analysis of Cdt1's function in suppressing nascent strand elongation during DNA replication in Xenopus egg extracts.

    Science.gov (United States)

    Nakazaki, Yuta; Tsuyama, Takashi; Azuma, Yutaro; Takahashi, Mikiko; Tada, Shusuke

    2017-09-02

    The initiation of DNA replication is strictly regulated by multiple mechanisms to ensure precise duplication of chromosomes. In higher eukaryotes, activity of the Cdt1 protein is temporally regulated during the cell cycle, and deregulation of Cdt1 induces DNA re-replication. In previous studies, we showed that excess Cdt1 inhibits DNA replication by suppressing progression of replication forks in Xenopus egg extracts. Here, we investigated the functional regions of Cdt1 that are required for the inhibition of DNA replication. We constructed a series of N-terminally or C-terminally deleted mutants of Cdt1 and examined their inhibitory effects on DNA replication in Xenopus egg extracts. Our results showed that the region spanning amino acids (a. a.) 255-620 is required for efficient inhibition of DNA replication, and that, within this region, a. a. 255-289 have a critical role in inhibition. Moreover, one of the Cdt1 mutants, Cdt1 R285A, was compromised with respect to the licensing activity but still inhibited DNA replication. This result suggests that Cdt1 has an unforeseen function in the negative regulation of DNA replication, and that this function is located within a molecular region that is distinct from those required for the licensing activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, Mohamed I., E-mail: mkhalil2@stanford.edu [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo (Egypt); Che, Xibing; Sung, Phillip; Sommer, Marvin H. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Hay, John [Department of Microbiology and Immunology, School of Medicine and Biomedical Science, University at Buffalo, Buffalo, NY (United States); Arvin, Ann M. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States)

    2016-05-15

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  12. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    International Nuclear Information System (INIS)

    Khalil, Mohamed I.; Che, Xibing; Sung, Phillip; Sommer, Marvin H.; Hay, John; Arvin, Ann M.

    2016-01-01

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  13. DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

    Science.gov (United States)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-06-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis

    DEFF Research Database (Denmark)

    Li, Shuxia; Christiansen, Lene; Christensen, Kaare

    2017-01-01

    Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated Cp...

  15. Replication Research in Comparative Genre Analysis in English for Academic Purposes

    Science.gov (United States)

    Basturkmen, Helen

    2014-01-01

    In recent years a number of comparative studies based on an established approach to genre analysis have been published in the English for Academic Purposes (EAP) literature. Studies in this emerging strand of research typically aim to identify how the rhetorical structure of a particular genre (a text type) or part of a genre may vary across…

  16. Timing Analysis of Genetic Logic Circuits using D-VASim

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    and propagation delay analysis of single as well as cascaded geneticlogic circuits can be performed. D-VASim allows user to change the circuit parameters during runtime simulation to observe its effectson circuit’s timing behavior. The results obtained from D-VASim can be used not only to characterize the timing...... delay analysis may play a very significant role in the designing of genetic logic circuits. In thisdemonstration, we present the capability of D-VASim (Dynamic Virtual Analyzer and Simulator) to perform the timing and propagationdelay analysis of genetic logic circuits. Using D-VASim, the timing...... behavior of geneticlogic circuits but also to analyze the timing constraints of cascaded genetic logic circuits....

  17. Multivariate genetic divergence among sugarcane clones by multivariate analysis associated with mixed models

    Directory of Open Access Journals (Sweden)

    Valéria Rosa Lopes

    2014-02-01

    Full Text Available This work had the aim to evaluate the genetic divergence in sugarcane clones using the methodology of graphic dispersion by principal components analysis associated to linear mixed models, indentifying the more divergent and productive genotypes with more precision, for a subsequent combination. 138 sugarcane clones of the RB97 series of the Sugarcane Breeding Program of the Universidade Federal do Parana, more two standard cultivars were evaluated in three environments, with two replications. The two first components explained 96% of the total variation, sufficiently for explaining the divergence found. The variable that contributed the most to de divergence was kilogram of brix per plot (BKP followed by brix, mass of 10 stalks and number of stalks per plot. The more divergent sugarcane clones were RB975008, RB975112, RB975019, RB975153 and RB975067 and the more productive clones were RB975269, RB977533, RB975102, RB975317 and RB975038.

  18. Smoking and caffeine consumption: a genetic analysis of their association.

    Science.gov (United States)

    Treur, Jorien L; Taylor, Amy E; Ware, Jennifer J; Nivard, Michel G; Neale, Michael C; McMahon, George; Hottenga, Jouke-Jan; Baselmans, Bart M L; Boomsma, Dorret I; Munafò, Marcus R; Vink, Jacqueline M

    2017-07-01

    Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. © 2016 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  19. Origin of life. Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers.

    Science.gov (United States)

    Maury, Carl Peter J

    2015-10-07

    The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and

  20. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  1. A roadmap for the genetic analysis of renal aging

    Science.gov (United States)

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-01-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. PMID:26219736

  2. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  3. A roadmap for the genetic analysis of renal aging.

    Science.gov (United States)

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-10-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. © 2015 The Authors. Aging Cell published by the Anatomical Society and John

  4. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  5. Three-dimensional quantitative structure-permeability relationship analysis for a series of inhibitors of rhinovirus replication.

    Science.gov (United States)

    Ekins, S; Durst, G L; Stratford, R E; Thorner, D A; Lewis, R; Loncharich, R J; Wikel, J H

    2001-01-01

    Multiple three-dimensional quantitative structure-activity relationship (3D-QSAR) approaches were applied to predicting passive Caco-2 permeability for a series of 28 inhibitors of rhinovirus replication. Catalyst, genetic function approximation (GFA) with MS-WHIM descriptors, CoMFA, and VolSurf were all used for generating 3D-quantitative structure permeability relationships utilizing a training set of 19 molecules. Each of these approaches was then compared using a test set of nine molecules not present in the training set. Statistical parameters for the test set predictions (r(2) and leave-one-out q(2)) were used to compare the models. It was found that the Catalyst pharmacophore model was the most predictive (test set of predicted versus observed permeability, r(2) = 0.94). This model consisted of a hydrogen bond acceptor, hydrogen bond donor, and ring aromatic feature with a training set correlation of r(2) = 0.83. The CoMFA model consisted of three components with an r(2) value of 0.96 and produced good predictions for the test set (r(2) = 0.84). VolSurf resulted in an r(2) value of 0.76 and good predictions for the test set (r(2) = 0.83). Test set predictions with GFA/WHIM descriptors (r(2) = 0.46) were inferior when compared with the Catalyst, CoMFA, and VolSurf model predictions in this evaluation. In summary it would appear that the 3D techniques have considerable value in predicting passive permeability for a congeneric series of molecules, representing a valuable asset for drug discovery.

  6. Genetic Interaction Mapping in Schizosaccharomyces pombe Using the Pombe Epistasis Mapper (PEM) System and a ROTOR HDA Colony Replicating Robot in a 1536 Array Format.

    Science.gov (United States)

    Roguev, Assen; Xu, Jiewei; Krogan, Nevan

    2018-02-01

    This protocol describes an optimized high-throughput procedure for generating double deletion mutants in Schizosaccharomyces pombe using the colony replicating robot ROTOR HDA and the PEM (pombe epistasis mapper) system. The method is based on generating high-density colony arrays (1536 colonies per agar plate) and passaging them through a series of antidiploid and mating-type selection (ADS-MTS) and double-mutant selection (DMS) steps. Detailed program parameters for each individual replication step are provided. Using this procedure, batches of 25 or more screens can be routinely performed. © 2018 Cold Spring Harbor Laboratory Press.

  7. A genetic analysis of retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Shanker Jayashree

    1993-01-01

    Full Text Available The data consists of sixty probands affected with Retinitis pigmentosa. Syndromic cases were found in five percent of the RP probands. Segregation analysis was carried out on proband sibship data. The ascertainment probability was estimated at 0.5517. Analysis of the data by parental mating types of proband sibships indicated the presence of dominant forms of RP (2.05%. Analysis of proband sibships indicated the presence of low risk families in the Normal x Normal matings (45% and in the consanguineous matings (40%. The hypothesis of recessive inheritance could be confirmed only in multiplex sibships (p = 0.383 +/- 0.0793. Data on proband matings though incomplete conformed in general to autosomal recessive gene hypothesis.

  8. A genetic analysis of Adh1 regulation

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-01-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  9. Genetic analysis for grain quality traits in pakistani wheat varieties

    International Nuclear Information System (INIS)

    Minhas, N.M.; Ajmal, S.U.; Iqbal, Z.; Munir, M.

    2014-01-01

    A set of eight parental diallel involving seven commercial wheat cultivars and one breeding line was made to investigate the nature of gene action determining inheritance pattern of grain quality characters. Highly significant differences were observed among the genotypes for 1000 grain weight, protein content, wet gluten and lysine content. Adequacy tests were employed to estimate the fitness of data sets to additive dominance model. Both the tests i.e. analysis of uniformity of Wr, Vr and joint regression analysis validated the data of these traits for genetic analysis. Gene actions for grain quality traits were ascertained following Hayman's analysis of variance. Results of the genetic analysis revealed that both additive and dominance genetic components were involved in the manifestation of characters under study. However, additive gene effects were more pronounced in the genetic control of these traits. Non significance of b1, b2 and b3 values revealed the absence of directional dominance, symmetrical distribution of genes among the parental lines and absence of specific genes action respectively in all the traits. Maternal effects were also noted in 1000 grain weight, protein content and wet gluten percentage. It is concluded that additive effects are crucial in the expression of grain quality characters of wheat in germplasm under study and single plant selection may be recommended in segregating generations for effective improvement in these characters. (author)

  10. Genetic analysis of repeated, biparental, diploid, hydatidiform moles

    DEFF Research Database (Denmark)

    Sunde, Lone; Vejerslev, Lars O.; Jensen, Mie Poulsen

    1993-01-01

    for the abnormal development can be envisaged, environmental as well as genetic. To conform to current ideas of molar pathogenesis, it is suggested that the present conceptuses might have arisen from imbalances in imprinted genomic regions. This could be a consequence of uniparental disomy in critical regions......A woman presented with five consecutive pregnancies displaying molar morphology. In the fifth pregnancy, a non-malformed, liveborn infant was delivered. Genetic analyses (RFLP analysis, cytogenetics, flow cytometry) were performed in pregnancies II-V. It was demonstrated that these pregnancies...... originated in separate conceptions, all conceptuses were diploid, and all had maternally as well as paternally derived genetic markers. By cytogenetic analysis, aberrant heteromorphisms were noted; no other abnormalities were observed in chromosome structure or in DNA sequence. Many different causes...

  11. SSR Analysis of Genetic Diversity Among 192 Diploid Potato Cultivars

    Directory of Open Access Journals (Sweden)

    Xiaoyan Song

    2016-05-01

    Full Text Available In potato breeding, it is difficult to improve the traits of interest at the tetraploid level due to the tetrasomic inheritance. A promising alternative is diploid breeding. Thus it is necessary to assess the genetic diversity of diploid potato germplasm for efficient exploration and deployment of desirable traits. In this study, we used SSR markers to evaluate the genetic diversity of diploid potato cultivars. To screen polymorphic SSR markers, 55 pairs of SSR primers were employed to amplify 39 cultivars with relatively distant genetic relationships. Among them, 12 SSR markers with high polymorphism located at 12 chromosomes were chosen to evaluate the genetic diversity of 192 diploid potato cultivars. The primers produced 6 to 18 bands with an average of 8.2 bands per primer. In total, 98 bands were amplified from 192 cultivars, and 97 of them were polymorphic. Cluster analysis using UPGMA showed the genetic relationships of all accessions tested: 186 of the 192 accessions could be distinguished by only 12 pairs of SSR primers, and the 192 diploid cultivars were divided into 11 groups, and 83.3% constituted the first group. Clustering results showed relatively low genetic diversity among 192 diploid cultivars, with closer relationship at the molecular level. The results can provide molecular basis for diploid potato breeding.

  12. Multivariate Methods for Meta-Analysis of Genetic Association Studies.

    Science.gov (United States)

    Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G

    2018-01-01

    Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.

  13. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    Science.gov (United States)

    Pharoah, Paul D. P.; Tsai, Ya-Yu; Ramus, Susan J.; Phelan, Catherine M.; Goode, Ellen L.; Lawrenson, Kate; Price, Melissa; Fridley, Brooke L.; Tyrer, Jonathan P.; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C.; Song, Honglin; Tessier, Daniel C.; Bacot, François; Vincent, Daniel; Cunningham, Julie M.; Dennis, Joe; Dicks, Ed; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M.; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brenton, James D.; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S.; Chang-Claude, Jenny; Chen, Y. Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S.; Coetzee, Gerhard; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K.; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Konecny, Gottfried E.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C.; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S.; van Altena, Anne M.; Berg, David Van Den; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T.; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N.A.; Gayther, Simon A.; Schildkraut, Joellen M.; Sellers, Thomas A.

    2013-01-01

    Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

  14. Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder – a meta-analysis of genetic studies

    Science.gov (United States)

    Byrne, Enda M; Raheja, Uttam; Stephens, Sarah H.; Heath, Andrew C; Madden, Pamela AF; Vaswani, Dipika; Nijjar, Gagan V.; Ryan, Kathleen A.; Youssufi, Hassaan; Gehrman, Philip R; Shuldiner, Alan R; Martin, Nicholas G; Montgomery, Grant W; Wray, Naomi R; Nelson, Elliot C; Mitchell, Braxton D; Postolache, Teodor T

    2015-01-01

    Objective To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. Methods A meta-analysis of genome-wide association studies (GWAS) conducted in Australian and Amish populations in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered. The total sample size was 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ) were calculated to test for overlap in risk between psychiatric disorders and seasonality. Results The most significant association was with rs11825064 (p = 1.7 × 10−6, β = 0.64, S.E = 0.13), an intergenic SNP found on chromosome 11. The evidence for overlap in risk factors was strongest for SCZ and seasonality, with the SCZ genetic profile scores explaining 3% of the variance in log-transformed GSS. BD genetic profile scores were also significantly associated with seasonality, although at much weaker levels, and no evidence for overlap in risk was detected between MDD and seasonality. Conclusions Common SNPs of very large effect likely do not exist for seasonality in the populations examined. As expected, there was overlapping genetic risk factors for BD (but not MDD) with seasonality. Unexpectedly, the risk for SCZ and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations, and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and SCZ PMID:25562672

  15. Genetic diversity of popcorn genotypes using molecular analysis.

    Science.gov (United States)

    Resh, F S; Scapim, C A; Mangolin, C A; Machado, M F P S; do Amaral, A T; Ramos, H C C; Vivas, M

    2015-08-19

    In this study, we analyzed dominant molecular markers to estimate the genetic divergence of 26 popcorn genotypes and evaluate whether using various dissimilarity coefficients with these dominant markers influences the results of cluster analysis. Fifteen random amplification of polymorphic DNA primers produced 157 amplified fragments, of which 65 were monomorphic and 92 were polymorphic. To calculate the genetic distances among the 26 genotypes, the complements of the Jaccard, Dice, and Rogers and Tanimoto similarity coefficients were used. A matrix of Dij values (dissimilarity matrix) was constructed, from which the genetic distances among genotypes were represented in a more simplified manner as a dendrogram generated using the unweighted pair-group method with arithmetic average. Clusters determined by molecular analysis generally did not group material from the same parental origin together. The largest genetic distance was between varieties 17 (UNB-2) and 18 (PA-091). In the identification of genotypes with the smallest genetic distance, the 3 coefficients showed no agreement. The 3 dissimilarity coefficients showed no major differences among their grouping patterns because agreement in determining the genotypes with large, medium, and small genetic distances was high. The largest genetic distances were observed for the Rogers and Tanimoto dissimilarity coefficient (0.74), followed by the Jaccard coefficient (0.65) and the Dice coefficient (0.48). The 3 coefficients showed similar estimations for the cophenetic correlation coefficient. Correlations among the matrices generated using the 3 coefficients were positive and had high magnitudes, reflecting strong agreement among the results obtained using the 3 evaluated dissimilarity coefficients.

  16. Single cell analysis of yeast replicative aging using a new generation of microfluidic device.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells.

  17. Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome.

    Science.gov (United States)

    Shen, Weiran; Deng, Xuefeng; Zou, Wei; Engelhardt, John F; Yan, Ziying; Qiu, Jianming

    2016-09-01

    Parvoviruses are single-stranded DNA viruses that use the palindromic structures at the ends of the viral genome for their replication. The mechanism of parvovirus replication has been studied mostly in the dependoparvovirus adeno-associated virus 2 (AAV2) and the protoparvovirus minute virus of mice (MVM). Here, we used human bocavirus 1 (HBoV1) to understand the replication mechanism of bocaparvovirus. HBoV1 is pathogenic to humans, causing acute respiratory tract infections, especially in young children under 2 years old. By using the duplex replicative form of the HBoV1 genome in human embryonic kidney 293 (HEK293) cells, we identified the HBoV1 minimal replication origin at the right-end hairpin (OriR). Mutagenesis analyses confirmed the putative NS1 binding and nicking sites within the OriR. Of note, unlike the large nonstructural protein (Rep78/68 or NS1) of other parvoviruses, HBoV1 NS1 did not specifically bind OriR in vitro, indicating that other viral and cellular components or the oligomerization of NS1 is required for NS1 binding to the OriR. In vivo studies demonstrated that residues responsible for NS1 binding and nicking are within the origin-binding domain. Further analysis identified that the small nonstructural protein NP1 is required for HBoV1 DNA replication at OriR. NP1 and other viral nonstructural proteins (NS1 to NS4) colocalized within the viral DNA replication centers in both OriR-transfected cells and virus-infected cells, highlighting a direct involvement of NP1 in viral DNA replication at OriR. Overall, our study revealed the characteristics of HBoV1 DNA replication at OriR, suggesting novel characteristics of autonomous parvovirus DNA replication. Human bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1

  18. A genetic analysis of Adhl regulation

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-01-01

    Several separate but related studies are reported on the mechanism of alcohol dehydrogenase (Adh-1) are reported. A study of a deletion mutation in the TATA box region which resulted in an increase from 6--60% of wildtype Adh-1 expression in the revertant has led to a focus on trans-acting protein factors that bind the TATA box. Analysis of another revertant has led to study of cis-acting sequences in Adh-1 expression. Screening efforts aimed at defining different mutants affecting Adh-1 expression are reported.

  19. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    The present study was conducted to assess the genetic diversity of Elite-II synthetic hexaploid (SH) wheat by genome DNA fingerprinting as revealed by random amplified polymorphic DNA (RAPD) analysis. Ten decamer RAPD primers (OPG-1, OPG-2, OPG-3, OPG-4, OPG-5, OPA-3, OPA-4, OPA-5, OPA-8, and OPA-15) ...

  20. Analysis of genetic diversity in pigeon pea germplasm using ...

    Indian Academy of Sciences (India)

    MANEESHA

    2017-08-16

    Aug 16, 2017 ... Th, Thailand; It, Italy; B, Barbados; Ta, Taiwan; J, Jamaica; V, Venezuela; UK, United Kingdom; My, Myanmar; U, Uganda; G,. Germany. .... from Orissa (105) and AP (15) do not group with any .... In the present work, comparison between SSAP and ... fied polymorphism) for genetic analysis of sweet potato.

  1. Genetic and phylogenetic analysis of ten Gobiidae species in China ...

    African Journals Online (AJOL)

    To study the genetic and phylogenetic relationship of gobioid fishes in China, the representatives of 10 gobioid fishes from 2 subfamilies in China were examined by amplified fragment length polymorphism (AFLP) analysis. We established 220 AFLP bands for 45 individuals from the 10 species, and the percentage of ...

  2. Genetic analysis on the competitive ability of barley ( Hordeum ...

    African Journals Online (AJOL)

    Genetic analysis on the competitive ability of barley ( Hordeum vulgare L.) recombinant inbred lines intercropped with oat ( Avena sativa L.) weeds. ... Furthermore, the commonly used herbicide price is soaring from time to time and out of the reach of the poor farmers in the developing countries. Therefore, this method is an ...

  3. Genetic analysis of feather pecking behavior in laying hens

    NARCIS (Netherlands)

    Buitenhuis, A.J.

    2003-01-01

    This thesis describes the genetic analysis of feather pecking behavior in laying hens. Feather pecking (FP) is a major welfare problem in laying hens.In the European

  4. Genetic analysis of yield in peanut (Arachis hypogaea L.) using ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... only should the two major genes' effects be considered but also the polygene's effect should be considered in breeding to increase peanut yield. Key words: Peanut, yield, major gene plus polygene inheritance model, genetic analysis. INTRODUCTION. Peanut consists of diploid (2n = 2x = 20), tetraploid ...

  5. Genetic analysis of yield in peanut ( Arachis hypogaea L.) using ...

    African Journals Online (AJOL)

    The yield had significant major gene effect and the results implied that not only should the two major genes' effects be considered but also the polygene's effect should be considered in breeding to increase peanut yield. Key words: Peanut, yield, major gene plus polygene inheritance model, genetic analysis.

  6. Genetic diversity analysis of pearl millet ( Pennisetum glauccum [L ...

    African Journals Online (AJOL)

    between genotype PT 2835/1 and PT 5552 and lowest similarity index was observed between PT 5554 and PT 2835/1. Analysis of RAPD data appears to be helpful in determining the genetic relationship among 20 pearl millet genotypes. The associations among the 20 genotypes were also examined with Principle ...

  7. The genetic analysis of repeated measures I: Simplex models

    NARCIS (Netherlands)

    Molenaar, P.C.M.; Boomsma, D.I.

    1987-01-01

    Extends the simplex model to a model that may be used for the genetic and environmental analysis of covariance (ANCOVA) structures. This "double" simplex structure can be specified as a linear structural relationships model. It is shown that data that give rise to a simplex correlation structure,

  8. Hemispheric lateralization in an analysis of speech sounds. Left hemisphere dominance replicated in Japanese subjects.

    Science.gov (United States)

    Koyama, S; Gunji, A; Yabe, H; Oiwa, S; Akahane-Yamada, R; Kakigi, R; Näätänen, R

    2000-09-01

    Evoked magnetic responses to speech sounds [R. Näätänen, A. Lehtokoski, M. Lennes, M. Cheour, M. Huotilainen, A. Iivonen, M. Vainio, P. Alku, R.J. Ilmoniemi, A. Luuk, J. Allik, J. Sinkkonen and K. Alho, Language-specific phoneme representations revealed by electric and magnetic brain responses. Nature, 385 (1997) 432-434.] were recorded from 13 Japanese subjects (right-handed). Infrequently presented vowels ([o]) among repetitive vowels ([e]) elicited the magnetic counterpart of mismatch negativity, MMNm (Bilateral, nine subjects; Left hemisphere alone, three subjects; Right hemisphere alone, one subject). The estimated source of the MMNm was stronger in the left than in the right auditory cortex. The sources were located posteriorly in the left than in the right auditory cortex. These findings are consistent with the results obtained in Finnish [R. Näätänen, A. Lehtokoski, M. Lennes, M. Cheour, M. Huotilainen, A. Iivonen, M.Vainio, P.Alku, R.J. Ilmoniemi, A. Luuk, J. Allik, J. Sinkkonen and K. Alho, Language-specific phoneme representations revealed by electric and magnetic brain responses. Nature, 385 (1997) 432-434.][T. Rinne, K. Alho, P. Alku, M. Holi, J. Sinkkonen, J. Virtanen, O. Bertrand and R. Näätänen, Analysis of speech sounds is left-hemisphere predominant at 100-150 ms after sound onset. Neuroreport, 10 (1999) 1113-1117.] and English [K. Alho, J.F. Connolly, M. Cheour, A. Lehtokoski, M. Huotilainen, J. Virtanen, R. Aulanko and R.J. Ilmoniemi, Hemispheric lateralization in preattentive processing of speech sounds. Neurosci. Lett., 258 (1998) 9-12.] subjects. Instead of the P1m observed in Finnish [M. Tervaniemi, A. Kujala, K. Alho, J. Virtanen, R.J. Ilmoniemi and R. Näätänen, Functional specialization of the human auditory cortex in processing phonetic and musical sounds: A magnetoencephalographic (MEG) study. Neuroimage, 9 (1999) 330-336.] and English [K. Alho, J. F. Connolly, M. Cheour, A. Lehtokoski, M. Huotilainen, J. Virtanen, R. Aulanko

  9. Quantitative analysis of replication-related mutation and selection pressures in bacterial chromosomes and plasmids using generalised GC skew index

    Directory of Open Access Journals (Sweden)

    Suzuki Haruo

    2009-12-01

    Full Text Available Abstract Background Due to their bi-directional replication machinery starting from a single finite origin, bacterial genomes show characteristic nucleotide compositional bias between the two replichores, which can be visualised through GC skew or (C-G/(C+G. Although this polarisation is used for computational prediction of replication origins in many bacterial genomes, the degree of GC skew visibility varies widely among different species, necessitating a quantitative measurement of GC skew strength in order to provide confidence measures for GC skew-based predictions of replication origins. Results Here we discuss a quantitative index for the measurement of GC skew strength, named the generalised GC skew index (gGCSI, which is applicable to genomes of any length, including bacterial chromosomes and plasmids. We demonstrate that gGCSI is independent of the window size and can thus be used to compare genomes with different sizes, such as bacterial chromosomes and plasmids. It can suggest the existence of different replication mechanisms in archaea and of rolling-circle replication in plasmids. Correlation of gGCSI values between plasmids and their corresponding host chromosomes suggests that within the same strain, these replicons have reproduced using the same replication machinery and thus exhibit similar strengths of replication strand skew. Conclusions gGCSI can be applied to genomes of any length and thus allows comparative study of replication-related mutation and selection pressures in genomes of different lengths such as bacterial chromosomes and plasmids. Using gGCSI, we showed that replication-related mutation or selection pressure is similar for replicons with similar machinery.

  10. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  11. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

    Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...

  12. System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability

    DEFF Research Database (Denmark)

    Xiao, Zhenyu; Chang, Jer-Gung; Hendriks, Ivo A

    2015-01-01

    . Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 hours of Hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and 2 proteins were down-regulated for SUMOylation, whereas after 24 hours, 35 proteins were up...

  13. Sex differences in distress from infidelity in early adulthood and in later life : A replication and meta-analysis of Shackelford et al.

    NARCIS (Netherlands)

    Ijzerman, H.; Blanken, I.; Brandt, M.J.; Oerlemans, H.; van den Hoogenhof, M; Franken, S.; Oerlemans, M.

    2014-01-01

    Shackelford and colleagues (2004) found that men, compared to women, are more distressed by sexual than emotional infidelity, and this sex difference continued into older age. We conducted four high-powered replications (total N = 1,952) of this effect and found different results. A meta-analysis of

  14. Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to "Megavirales".

    Science.gov (United States)

    Mushegian, Arcady; Karin, Eli Levy; Pupko, Tal

    2018-01-01

    The order Herpesvirales includes animal viruses with large double-strand DNA genomes replicating in the nucleus. The main capsid protein in the best-studied family Herpesviridae contains a domain with HK97-like fold related to bacteriophage head proteins, and several virion maturation factors are also homologous between phages and herpesviruses. The origin of herpesvirus DNA replication proteins is less well understood. While analyzing the genomes of herpesviruses in the family Malacohepresviridae, we identified nearly 30 families of proteins conserved in other herpesviruses, including several phage-related domains in morphogenetic proteins. Herpesvirus DNA replication factors have complex evolutionary history: some are related to cellular proteins, but others are closer to homologs from large nucleocytoplasmic DNA viruses. Phylogenetic analyses suggest that the core replication machinery of herpesviruses may have been recruited from the same pool as in the case of other large DNA viruses of eukaryotes. Published by Elsevier Inc.

  15. Strand-Specific Analysis of DNA Synthesis and Proteins Association with DNA Replication Forks in Budding Yeast.

    Science.gov (United States)

    Yu, Chuanhe; Gan, Haiyun; Zhang, Zhiguo

    2018-01-01

    DNA replication initiates at DNA replication origins after unwinding of double-strand DNA(dsDNA) by replicative helicase to generate single-stranded DNA (ssDNA) templates for the continuous synthesis of leading-strand and the discontinuous synthesis of lagging-strand. Therefore, methods capable of detecting strand-specific information will likely yield insight into the association of proteins at leading and lagging strand of DNA replication forks and the regulation of leading and lagging strand synthesis during DNA replication. The enrichment and Sequencing of Protein-Associated Nascent DNA (eSPAN), which measure the relative amounts of proteins at nascent leading and lagging strands of DNA replication forks, is a step-wise procedure involving the chromatin immunoprecipitation (ChIP) of a protein of interest followed by the enrichment of protein-associated nascent DNA through BrdU immunoprecipitation. The isolated ssDNA is then subjected to strand-specific sequencing. This method can detect whether a protein is enriched at leading or lagging strand of DNA replication forks. In addition to eSPAN, two other strand-specific methods, (ChIP-ssSeq), which detects potential protein-ssDNA binding and BrdU-IP-ssSeq, which can measure synthesis of both leading and lagging strand, were developed along the way. These methods can provide strand-specific and complementary information about the association of the target protein with DNA replication forks as well as synthesis of leading and lagging strands genome wide. Below, we describe the detailed eSPAN, ChIP-ssSeq, and BrdU-IP-ssSeq protocols.

  16. Analysis of genetic diversity in Bolivian llama populations using microsatellites.

    Science.gov (United States)

    Barreta, J; Gutiérrez-Gil, B; Iñiguez, V; Romero, F; Saavedra, V; Chiri, R; Rodríguez, T; Arranz, J J

    2013-08-01

    South American camelids (SACs) have a major role in the maintenance and potential future of rural Andean human populations. More than 60% of the 3.7 million llamas living worldwide are found in Bolivia. Due to the lack of studies focusing on genetic diversity in Bolivian llamas, this analysis investigates both the genetic diversity and structure of 12 regional groups of llamas that span the greater part of the range of distribution for this species in Bolivia. The analysis of 42 microsatellite markers in the considered regional groups showed that, in general, there were high levels of polymorphism (a total of 506 detected alleles; average PIC across per marker: 0.66), which are comparable with those reported for other populations of domestic SACs. The estimated diversity parameters indicated that there was high intrapopulational genetic variation (average number of alleles and average expected heterozygosity per marker: 12.04 and 0.68, respectively) and weak genetic differentiation among populations (FST range: 0.003-0.052). In agreement with these estimates, Bolivian llamas showed a weak genetic structure and an intense gene flow between all the studied regional groups, which is due to the exchange of reproductive males between the different flocks. Interestingly, the groups for which the largest pairwise FST estimates were observed, Sud Lípez and Nor Lípez, showed a certain level of genetic differentiation that is probably due to the pattern of geographic isolation and limited communication infrastructures of these southern localities. Overall, the population parameters reported here may serve as a reference when establishing conservation policies that address Bolivian llama populations. © 2012 Blackwell Verlag GmbH.

  17. Genetic Diversity of Infectious Laryngotracheitis Virus during In Vivo Coinfection Parallels Viral Replication and Arises from Recombination Hot Spots within the Genome.

    Science.gov (United States)

    Loncoman, Carlos A; Hartley, Carol A; Coppo, Mauricio J C; Vaz, Paola K; Diaz-Méndez, Andrés; Browning, Glenn F; García, Maricarmen; Spatz, Stephen; Devlin, Joanne M

    2017-12-01

    Recombination is a feature of many alphaherpesviruses that infect people and animals. Infectious laryngotracheitis virus (ILTV; Gallid alphaherpesvirus 1 ) causes respiratory disease in chickens, resulting in significant production losses in poultry industries worldwide. Natural (field) ILTV recombination is widespread, particularly recombination between attenuated ILTV vaccine strains to create virulent viruses. These virulent recombinants have had a major impact on animal health. Recently, the development of a single nucleotide polymorphism (SNP) genotyping assay for ILTV has helped to understand ILTV recombination in laboratory settings. In this study, we applied this SNP genotyping assay to further examine ILTV recombination in the natural host. Following coinoculation of specific-pathogen-free chickens, we examined the resultant progeny for evidence of viral recombination and characterized the diversity of the recombinants over time. The results showed that ILTV replication and recombination are closely related and that the recombinant viral progeny are most diverse 4 days after coinoculation, which is the peak of viral replication. Further, the locations of recombination breakpoints in a selection of the recombinant progeny, and in field isolates of ILTV from different geographical regions, were examined following full-genome sequencing and used to identify recombination hot spots in the ILTV genome. IMPORTANCE Alphaherpesviruses are common causes of disease in people and animals. Recombination enables genome diversification in many different species of alphaherpesviruses, which can lead to the evolution of higher levels of viral virulence. Using the alphaherpesvirus infectious laryngotracheitis virus (ILTV), we performed coinfections in the natural host (chickens) to demonstrate high levels of virus recombination. Higher levels of diversity in the recombinant progeny coincided with the highest levels of virus replication. In the recombinant progeny, and in

  18. Database Replication Prototype

    OpenAIRE

    Vandewall, R.

    2000-01-01

    This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....

  19. A markerless protocol for genetic analysis of Aggregatibacter actinomycetemcomitans

    Science.gov (United States)

    Cheng, Ya-An; Jee, Jason; Hsu, Genie; Huang, Yanyan; Chen, Casey; Lin, Chun-Pin

    2015-01-01

    Background/Purpose The genomes of different Aggregatibacter actinomycetemcomitans strains contain many strain-specific genes and genomic islands (defined as DNA found in some but not all strains) of unknown functions. Genetic analysis for the functions of these islands will be constrained by the limited availability of genetic markers and vectors for A. actinomycetemcomitans. In this study we tested a novel genetic approach of gene deletion and restoration in a naturally competent A. actinomycetemcomitans strain D7S-1. Methods Specific genes’ deletion mutants and mutants restored with the deleted genes were constructed by a markerless loxP/Cre system. In mutants with sequential deletion of multiple genes loxP with different spacer regions were used to avoid unwanted recombinations between loxP sites. Results Eight single-gene deletion mutants, four multiple-gene deletion mutants, and two mutants with restored genes were constructed. No unintended non-specific deletion mutants were generated by this protocol. The protocol did not negatively affect the growth and biofilm formation of A. actinomycetemcomitans. Conclusion The protocol described in this study is efficient and specific for genetic manipulation of A. actinomycetemcomitans, and will be amenable for functional analysis of multiple genes in A. actinomycetemcomitans. PMID:24530245

  20. A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents.

    Science.gov (United States)

    Maes, Hermine H; Prom-Wormley, Elizabeth; Eaves, Lindon J; Rhee, Soo Hyun; Hewitt, John K; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G; Legrand, Lisa; Samek, Diana R; Murrelle, E Lenn; Silberg, Judy L; Miles, Donna R; Schieken, Richard M; Beunen, Gaston P; Thomis, Martine; Rose, Richard J; Dick, Danielle M; Boomsma, Dorret I; Bartels, Meike; Vink, Jacqueline M; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C

    2017-04-01

    Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across

  1. Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

    Science.gov (United States)

    Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

    2016-08-19

    Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

    Science.gov (United States)

    Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

    2014-07-01

    About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

  3. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major

    Directory of Open Access Journals (Sweden)

    Rodrigo Lombraña

    2016-08-01

    Full Text Available Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs. Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance.

  4. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  5. Differential network analysis reveals genetic effects on catalepsy modules.

    Directory of Open Access Journals (Sweden)

    Ovidiu D Iancu

    Full Text Available We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS formed by crossing four inbred strains (HS4 and a heterogeneous stock (HS-CC formed from the inbred strain founders of the Collaborative Cross (CC. All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.

  6. Genetic analysis of growth traits in Iranian Makuie sheep breed

    Directory of Open Access Journals (Sweden)

    Mohammad Farhadian

    2012-01-01

    Full Text Available The Makuie sheep is a fat-tailed sheep breed which can be found in the Azerbaijan province of Iran. In 1986, a Makuie sheep breeding station was established in the city of Maku in order to breed, protect and purify this breed. The genetic parameters for birth weight, weaning weight (3 months, 6-month, 9-month and yearling weight, and average daily gain from birth to weaning traits were estimated based on 25 years of data using DFREML software. Six different models were applied and a likelihood ratio test (LRT was used to select the appropriate model. Bivariate analysis was used to define the genetic correlation between studied traits. Based on the LRT, model II was selected as an appropriate model for all studied traits. Direct heritability estimates of birth, weaning, 6-month, 9-month and yearling weights and average daily gain from birth to weaning were 0.36, 0.41, 0.48, 0.42, 0.36 and 0.37, respectively. Estimates of direct genetic correlation between birth and weaning weights, birth and 6-month weights, birth and 9-month weights, as well as between birth and yearling weights were 0.57, 0.49, 0.46 and 0.32, respectively. The results suggest there is a substantial additive genetic variability for studied traits in the Makuie sheep breed population, and the direct additive effect and maternal permanent environment variance are the main source of phenotypic variance.

  7. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  8. Methodological issues of genetic association studies.

    Science.gov (United States)

    Simundic, Ana-Maria

    2010-12-01

    Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

  9. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  10. Imaging genetics paradigms in depression research: Systematic review and meta-analysis.

    Science.gov (United States)

    Pereira, Lícia P; Köhler, Cristiano A; Stubbs, Brendon; Miskowiak, Kamilla W; Morris, Gerwyn; de Freitas, Bárbara P; Thompson, Trevor; Fernandes, Brisa S; Brunoni, André R; Maes, Michael; Pizzagalli, Diego A; Carvalho, André F

    2018-05-17

    Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30th, 2017. Sixty-five studies met eligibility criteria (N = 4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included studies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met 'Met' (386 participants with MDD and 376 controls) or the 5-HTTLPR short 'S' (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short 'S' alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met 'Met' risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short 'S' allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met 'Met' allele had larger gray matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that

  11. Fusion genetic analysis of jasmonate-signalling mutants in Arabidopsis

    DEFF Research Database (Denmark)

    Jensen, Anders Bøgh; Raventos, D.; Mundy, John Williams

    2002-01-01

    as two recessive mutants, designated joe1 and 2, that overexpress the reporter. Genetic analysis indicated that reporter overexpression in the joe mutants requires COI. joe1 responded to MeJA with increased anthocyanin accumulation, while joe2 responded with decreased root growth inhibition. In addition...... activity was also induced by the protein kinase inhibitor staurosporine and antagonized by the protein phosphatase inhibitor okadaic acid. FLUC bio-imaging, RNA gel-blot analysis and progeny analyses identified three recessive mutants that underexpress the FLUC reporter, designated jue1, 2 and 3, as well...

  12. DMPD: The Toll-like receptors: analysis by forward genetic methods. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16001129 The Toll-like receptors: analysis by forward genetic methods. Beutler B. I...mmunogenetics. 2005 Jul;57(6):385-92. (.png) (.svg) (.html) (.csml) Show The Toll-like receptors: analysis by forwar...d genetic methods. PubmedID 16001129 Title The Toll-like receptors: analysis by forward genetic meth

  13. Prelife catalysts and replicators

    OpenAIRE

    Ohtsuki, Hisashi; Nowak, Martin A.

    2009-01-01

    Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...

  14. Single Cell Analysis of Human RAD18-Dependent DNA Post-Replication Repair by Alkaline Bromodeoxyuridine Comet Assay

    Science.gov (United States)

    Mórocz, Mónika; Gali, Himabindu; Raskó, István; Downes, C. Stephen; Haracska, Lajos

    2013-01-01

    Damage to DNA can block replication progression resulting in gaps in the newly synthesized DNA. Cells utilize a number of post-replication repair (PRR) mechanisms such as the RAD18 controlled translesion synthesis or template switching to overcome the discontinuities formed opposite the DNA lesions and to complete DNA replication. Gaining more insights into the role of PRR genes promotes better understanding of DNA damage tolerance and of how their malfunction can lead to increased genome instability and cancer. However, a simple and efficient method to characterise gene specific PRR deficiencies at a single cell level has not been developed. Here we describe the so named BrdU comet PRR assay to test the contribution of human RAD18 to PRR at a single cell level, by which we kinetically characterized the consequences of the deletion of human RAD18 on the replication of UV-damaged DNA. Moreover, we demonstrate the capability of our method to evaluate PRR at a single cell level in unsynchronized cell population. PMID:23936422

  15. Deletion analysis of cis- and trans-acting elements involved in replication of alfalfa mosaic virus RNA 3 in vivo

    NARCIS (Netherlands)

    van der Kuyl, A. C.; Neeleman, L.; Bol, J. F.

    1991-01-01

    DNA copies of alfalfa mosaic virus (AIMV) RNA 3 were transcribed in vitro into RNA molecules with deletions in coding and noncoding sequences. The replication of these transcripts was studied in protoplasts from transgenic tobacco plants expressing DNA copies of AIMV RNAs 1 and 2. Deletions in the

  16. Genetic algorithms and the analysis of SnIa data

    International Nuclear Information System (INIS)

    Nesseris, Savvas

    2011-01-01

    The Genetic Algorithm is a heuristic that can be used to produce model independent solutions to an optimization problem, thus making it ideal for use in cosmology and more specifically in the analysis of type Ia supernovae data. In this work we use the Genetic Algorithms (GA) in order to derive a null test on the spatially flat cosmological constant model ΛCDM. This is done in two steps: first, we apply the GA to the Constitution SNIa data in order to acquire a model independent reconstruction of the expansion history of the Universe H(z) and second, we use the reconstructed H(z) in conjunction with the Om statistic, which is constant only for the ΛCDM model, to derive our constraints. We find that while ΛCDM is consistent with the data at the 2σ level, some deviations from ΛCDM model at low redshifts can be accommodated.

  17. DNA degradation and genetic analysis of empty puparia: genetic identification limits in forensic entomology.

    Science.gov (United States)

    Mazzanti, Morena; Alessandrini, Federica; Tagliabracci, Adriano; Wells, Jeffrey D; Campobasso, Carlo P

    2010-02-25

    Puparial cases are common remnants of necrophagous flies in crime investigations. They usually represent the longest developmental time and, therefore, they can be very useful for the estimation of the post-mortem interval (PMI). However, before any PMI estimate, it is crucial to identify the species of fly eclosed from each puparium associated with the corpse. Morphological characteristics of the puparium are often distinctive enough to permit a species identification. But, even an accurate morphological analysis of empty puparia cannot discriminate among different species of closely related flies. Furthermore, morphological identification may be impossible if the fly puparia are poorly preserved or in fragments. This study explores the applicability of biomolecular techniques on empty puparia and their fragments for identification purposes. A total of 63 empty puparia of necrophagous Diptera resulting from forensic casework were examined. Samples were divided into three groups according to size, type and time of eclosion in order to verify whether the physical characteristics and puparia weathering can influence the amount of DNA extraction. The results suggest that a reliable genetic identification of forensically important flies may also be performed from empty puparia and/or their fragments. However, DNA degradation can deeply compromise the genetic analysis since the older the fly puparia, the smaller are the amplified fragments. 2009 Elsevier Ireland Ltd. All rights reserved.

  18. Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies.

    Directory of Open Access Journals (Sweden)

    Soma Ghosh

    Full Text Available 5-Fluorouracil (5FU, a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms. Prior studies implicated a VNTR (variable numbers of tandem repeats polymorphism in the 5'-untranslated region (5'-UTR of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T repeats and novel single nucleotide polymorphisms (SNPs flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt, polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing.

  19. Mapping autonomously replicating sequence elements in a 73-kb ...

    Indian Academy of Sciences (India)

    Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards identifying all potential replication origins in a 73-kb region of the long arm ...

  20. Replication and meta-analysis of common variants identifies a genome-wide significant locus in migraine

    DEFF Research Database (Denmark)

    Esserlind, A-L; Christensen, A F; Le, H

    2013-01-01

    Genetic factors contribute to the aetiology of the prevalent form of migraine without aura (MO) and migraine with typical aura (MTA). Due to the complex inheritance of MO and MTA, the genetic background is still not fully established. In a population-based genome-wide association study by Chasman...

  1. Diallel Analysis using Hayman Method to Study Genetic Parameters of Yield Components in Pepper(Capsicum annuum L.

    Directory of Open Access Journals (Sweden)

    MUHAMAD SYUKUR

    2010-12-01

    Full Text Available One method to obtain genetic information is the diallel cross analysis. The objective of this study was to eavluate the genetic parameters of six inbred pepper (Capsicum annuum L. using full diallel crosses. The experiment was conducted at IPB Experiment Field, Cikabayan, Darmaga. The design was randomized complete block design (RCBD using three replications as blocks. Data from generation F1 and parents were analyzed using the Hayman Method. Results indicated that no epistatic effects were significant for all the traits assessed. Additive genetic effects were larger than the dominant effects for yield per plant, fruit length, and diameter fruit traits. Dominant genetic effects were larger than the additive effects for fruit weight traits. Narrow-sense and broad-sense heritability were high for all the traits assessed. The character of the yield per plant, fruit weight and fruit diameter shows that there were more dominant genes in the parents. There were more recessive genes in parents for the fruit length character. IPB C7 parent was the most recessive genes containing control characters in the yield per plant. In the new improved varieties of high yielding, IPB C7 could be crossed with IPB C9. Employing individual or mass selection breeding should be successful in developing high-productivity lines in this population.

  2. A hybrid correlation analysis with application to imaging genetics

    Science.gov (United States)

    Hu, Wenxing; Fang, Jian; Calhoun, Vince D.; Wang, Yu-Ping

    2018-03-01

    Investigating the association between brain regions and genes continues to be a challenging topic in imaging genetics. Current brain region of interest (ROI)-gene association studies normally reduce data dimension by averaging the value of voxels in each ROI. This averaging may lead to a loss of information due to the existence of functional sub-regions. Pearson correlation is widely used for association analysis. However, it only detects linear correlation whereas nonlinear correlation may exist among ROIs. In this work, we introduced distance correlation to ROI-gene association analysis, which can detect both linear and nonlinear correlations and overcome the limitation of averaging operations by taking advantage of the information at each voxel. Nevertheless, distance correlation usually has a much lower value than Pearson correlation. To address this problem, we proposed a hybrid correlation analysis approach, by applying canonical correlation analysis (CCA) to the distance covariance matrix instead of directly computing distance correlation. Incorporating CCA into distance correlation approach may be more suitable for complex disease study because it can detect highly associated pairs of ROI and gene groups, and may improve the distance correlation level and statistical power. In addition, we developed a novel nonlinear CCA, called distance kernel CCA, which seeks the optimal combination of features with the most significant dependence. This approach was applied to imaging genetic data from the Philadelphia Neurodevelopmental Cohort (PNC). Experiments showed that our hybrid approach produced more consistent results than conventional CCA across resampling and both the correlation and statistical significance were increased compared to distance correlation analysis. Further gene enrichment analysis and region of interest (ROI) analysis confirmed the associations of the identified genes with brain ROIs. Therefore, our approach provides a powerful tool for finding

  3. Genetic Analysis of Oncorhynchus Nerka : Life History and Genetic Analysis of Redfish Lake Oncorhynchus Nerka, 1993-1994 Completion Report.

    Energy Technology Data Exchange (ETDEWEB)

    Brannon, E.L.; Thorgaard, G.H.; Cummings, S.A.

    1994-10-01

    The study has shown through life history examination and DNA analysis that three forms of O. nerka are present in Redfish Lake. The three forms are closely related, but may be sufficiently different to be considered three separate stocks. Fishhook Creek kokanee are temporally isolated from the beach spawners, and may represent the gene pool most similar to the historic sockeye population that once spawned there. Fishhook Creek offers the best spawning area available in the lake system, and should be considered for use in reestablishing an anadromous Fishhook Creek sockeye swain. The resident beach spawning strain of O. nerka is likewise the most similar genetic form of the companion anadromous beach spawning O. nerka, and needs to be considered the most appropriate genetic source to help minimize reduced fitness of the sockeye from inbreeding.

  4. Analysis of conditional genetic effects and variance components in developmental genetics.

    Science.gov (United States)

    Zhu, J

    1995-12-01

    A genetic model with additive-dominance effects and genotype x environment interactions is presented for quantitative traits with time-dependent measures. The genetic model for phenotypic means at time t conditional on phenotypic means measured at previous time (t-1) is defined. Statistical methods are proposed for analyzing conditional genetic effects and conditional genetic variance components. Conditional variances can be estimated by minimum norm quadratic unbiased estimation (MINQUE) method. An adjusted unbiased prediction (AUP) procedure is suggested for predicting conditional genetic effects. A worked example from cotton fruiting data is given for comparison of unconditional and conditional genetic variances and additive effects.

  5. Genetic analysis of the heparan modification network in Caenorhabditis elegans.

    Science.gov (United States)

    Townley, Robert A; Bülow, Hannes E

    2011-05-13

    Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans.

  6. Genetic Analysis of the Heparan Modification Network in Caenorhabditis elegans*

    Science.gov (United States)

    Townley, Robert A.; Bülow, Hannes E.

    2011-01-01

    Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans. PMID:21454666

  7. Genetic analysis of bulimia nervosa: methods and sample description.

    Science.gov (United States)

    Kaye, Walter H; Devlin, Bernie; Barbarich, Nicole; Bulik, Cynthia M; Thornton, Laura; Bacanu, Silviu-Alin; Fichter, Manfred M; Halmi, Katherine A; Kaplan, Allan S; Strober, Michael; Woodside, D Blake; Bergen, Andrew W; Crow, Scott; Mitchell, James; Rotondo, Alessandro; Mauri, Mauro; Cassano, Giovanni; Keel, Pamela; Plotnicov, Katherine; Pollice, Christine; Klump, Kelly L; Lilenfeld, Lisa R; Ganjei, J Kelly; Quadflieg, Norbert; Berrettini, Wade H

    2004-05-01

    Twin and family studies suggest that genetic variants contribute to the pathogenesis of bulimia nervosa (BN) and anorexia nervosa (AN). The Price Foundation has supported an international, multisite study of families with these disorders to identify these genetic variations. The current study presents the clinical characteristics of this sample as well as a description of the study methodology. All probands met modified criteria for BN or bulimia nervosa with a history of AN (BAN) as defined in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994). All affected relatives met DSM-IV criteria for BN, AN, BAN, or eating disorders not otherwise specified (EDNOS). Probands and affected relatives were assessed diagnostically using both trained-rater and self-report assessments. DNA samples were collected from probands, affected relatives, and available biologic parents. Assessments were obtained from 163 BN probands and 165 BAN probands. Overall, there were 365 relative pairs available for linkage analysis. Of the affected relatives of BN probands, 62 were diagnosed as BN (34.8%), 49 as BAN (27.5%), 35 as AN (19.7%), and 32 as EDNOS (18.0%). For the relatives of BAN probands, 42 were diagnosed as BN (22.5%), 67 as BAN (35.8%), 48 as AN (25.7%), and 30 as EDNOS (16.0%). This study represents the largest genetic study of eating disorders to date. Clinical data indicate that although there are a large number of individuals with BN disorders, a range of eating pathology is represented in the sample, allowing for the examination of several different phenotypes in molecular genetic analyses. Copyright 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 556-570, 2004.

  8. Population genetic analysis of Enterocytozoon bieneusi in humans.

    Science.gov (United States)

    Li, Wei; Cama, Vitaliano; Feng, Yaoyu; Gilman, Robert H; Bern, Caryn; Zhang, Xichen; Xiao, Lihua

    2012-01-01

    Genotyping based on sequence analysis of the ribosomal internal transcribed spacer has revealed significant genetic diversity in Enterocytozoonbieneusi. Thus far, the population genetics of E. bieneusi and its significance in the epidemiology of microsporidiosis have not been examined. In this study, a multilocus sequence typing of E. bieneusi in AIDS patients in Lima, Peru was conducted, using 72 specimens previously genotyped as A, D, IV, EbpC, WL11, Peru7, Peru8, Peru10 and Peru11 at the internal transcribed spacer locus. Altogether, 39 multilocus genotypes were identified among the 72 specimens. The observation of strong intragenic linkage disequilibria and limited genetic recombination among markers were indicative of an overall clonal population structure of E. bieneusi. Measures of pair-wise intergenic linkage disequilibria and a standardised index of association (IAS) based on allelic profile data further supported this conclusion. Both sequence-based and allelic profile-based phylogenetic analyses showed the presence of two genetically isolated groups in the study population, one (group 1) containing isolates of the anthroponotic internal transcribed spacer genotype A, and the other (group 2) containing isolates of multiple internal transcribed spacer genotypes (mainly genotypes D and IV) with zoonotic potential. The measurement of linkage disequilibria and recombination indicated group 2 had a clonal population structure, whereas group 1 had an epidemic population structure. The formation of the two sub-populations was confirmed by STRUCTURE and Wright's fixation index (FST) analyses. The data highlight the power of MLST in understanding the epidemiology of E. bieneusi. Published by Elsevier Ltd.

  9. In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.

    Science.gov (United States)

    Lindsey-Boltz, Laura A; Reardon, Joyce T; Wold, Marc S; Sancar, Aziz

    2012-10-19

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair.

  10. In Vitro Analysis of the Role of Replication Protein A (RPA) and RPA Phosphorylation in ATR-mediated Checkpoint Signaling*

    Science.gov (United States)

    Lindsey-Boltz, Laura A.; Reardon, Joyce T.; Wold, Marc S.; Sancar, Aziz

    2012-01-01

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair. PMID:22948311

  11. Assessment and improvement of statistical tools for comparative proteomics analysis of sparse data sets with few experimental replicates

    DEFF Research Database (Denmark)

    Schwämmle, Veit; León, Ileana R.; Jensen, Ole Nørregaard

    2013-01-01

    Large-scale quantitative analyses of biological systems are often performed with few replicate experiments, leading to multiple nonidentical data sets due to missing values. For example, mass spectrometry driven proteomics experiments are frequently performed with few biological or technical...... replicates due to sample-scarcity or due to duty-cycle or sensitivity constraints, or limited capacity of the available instrumentation, leading to incomplete results where detection of significant feature changes becomes a challenge. This problem is further exacerbated for the detection of significant...... as a novel and optimal way to detect significantly changing features in these data sets. This approach is suitable for large quantitative data sets from stable isotope labeling and mass spectrometry experiments and should be applicable to large data sets of any type. An R script that implements the improved...

  12. A cluster analysis on road traffic accidents using genetic algorithms

    Science.gov (United States)

    Saharan, Sabariah; Baragona, Roberto

    2017-04-01

    The analysis of traffic road accidents is increasingly important because of the accidents cost and public road safety. The availability or large data sets makes the study of factors that affect the frequency and severity accidents are viable. However, the data are often highly unbalanced and overlapped. We deal with the data set of the road traffic accidents recorded in Christchurch, New Zealand, from 2000-2009 with a total of 26440 accidents. The data is in a binary set and there are 50 factors road traffic accidents with four level of severity. We used genetic algorithm for the analysis because we are in the presence of a large unbalanced data set and standard clustering like k-means algorithm may not be suitable for the task. The genetic algorithm based on clustering for unknown K, (GCUK) has been used to identify the factors associated with accidents of different levels of severity. The results provided us with an interesting insight into the relationship between factors and accidents severity level and suggest that the two main factors that contributes to fatal accidents are "Speed greater than 60 km h" and "Did not see other people until it was too late". A comparison with the k-means algorithm and the independent component analysis is performed to validate the results.

  13. EMBO Course “Formal Analysis of Genetic Regulation”

    CERN Document Server

    1979-01-01

    The E M B 0 course on "Formal Analysis of Genetic Regulation" A course entitled "Formal analysis of Genetic Regulation" was held at the University of Brussels from 6 to 16 September 1977 under the auspices of EMBO (European Molecular Biology Organization). As indicated by the title of the book (but not explicitly enough by the title of the course), the main emphasis was put on a dynamic analysis of systems using logical methods, that is, methods in which functions and variables take only a limited number of values - typically two. In this respect, this course was complementary to an EMBO course using continuous methods which was held some months later in Israel by Prof. Segel. People from four very different laboratories took an active part in teaching our course in Brussels : Drs Anne LEUSSLER and Philippe VAN HAM, from the Laboratory of Prof. Jean FLORINE (Laboratoire des Systemes logiques et numeriques, Faculte des Sciences appliquees, Universite Libre de Bruxelles). Dr Stuart KAUFFMAN (Dept. of Biochemist...

  14. Genetic analysis of fibre quality traits in upland cotton

    International Nuclear Information System (INIS)

    Khan, I.A.; Shakeel, A.; Azhar, F.M.

    2001-01-01

    Five-parent diallel cross data were analysed following Hayman-Jinks genetic model in order to study pattern of inheritance of staple length, fibre strength, fibre fineness and fibre uniformity of upland cotton. The regression analysis of the F/sub 1/ data revealed that the simple additive dominance model was adequate for genetic analysis. Graphic analysis showed the presence of over-dominance type of gene action in the inheritance e of all the traits. The comparison of array means indicated that varieties Co-2-1 and B-682 had good general combining ability for staple length and fibre strength respectively, whilst CIM-443 showed better general combining ability for fibre fineness and fibre uniformity than the other varieties. The cross combination of Co-2-1 and CIM-443 with B-682 expressed best specific combining ability for staple length and fibre uniformity respectively. Similarly variety B-682 nickel well with DPL 7740-424 for the fibre strength, and coker-307 with CO-2-1 for fibre fineness. The type of gene action controlling inheritance of these characters, and better performance of some of the hybrids suggest that improvement may be possible by developing on appropriate breeding programme. (author)

  15. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

    Science.gov (United States)

    Kumar, Sudhir; Stecher, Glen; Li, Michael; Knyaz, Christina; Tamura, Koichiro

    2018-06-01

    The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.

  16. [Wolfram syndrome: clinical and genetic analysis in two sisters].

    Science.gov (United States)

    Conart, J-B; Maalouf, T; Jonveaux, P; Guerci, B; Angioi, K

    2011-10-01

    Wolfram syndrome is a severe genetic disorder defined by the association of diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Two sisters complained of progressive visual loss. Fundus examination evidenced optic atrophy. Their past medical history revealed diabetes mellitus and deafness since childhood. The association of these symptoms made the diagnosis of Wolfram syndrome possible. It was confirmed by molecular analysis, which evidenced composite WFS1 heterozygous mutations inherited from both their mother and father. Ophthalmologists should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. Comparative genome analysis of a thermotolerant Escherichia coli obtained by Genome Replication Engineering Assisted Continuous Evolution (GREACE) and its parent strain provides new understanding of microbial heat tolerance.

    Science.gov (United States)

    Luan, Guodong; Bao, Guanhui; Lin, Zhao; Li, Yang; Chen, Zugen; Li, Yin; Cai, Zhen

    2015-12-25

    Heat tolerance of microbes is of great importance for efficient biorefinery and bioconversion. However, engineering and understanding of microbial heat tolerance are difficult and insufficient because it is a complex physiological trait which probably correlates with all gene functions, genetic regulations, and cellular metabolisms and activities. In this work, a novel strain engineering approach named Genome Replication Engineering Assisted Continuous Evolution (GREACE) was employed to improve the heat tolerance of Escherichia coli. When the E. coli strain carrying a mutator was cultivated under gradually increasing temperature, genome-wide mutations were continuously generated during genome replication and the mutated strains with improved thermotolerance were autonomously selected. A thermotolerant strain HR50 capable of growing at 50°C on LB agar plate was obtained within two months, demonstrating the efficiency of GREACE in improving such a complex physiological trait. To understand the improved heat tolerance, genomes of HR50 and its wildtype strain DH5α were sequenced. Evenly distributed 361 mutations covering all mutation types were found in HR50. Closed material transportations, loose genome conformation, and possibly altered cell wall structure and transcription pattern were the main differences of HR50 compared with DH5α, which were speculated to be responsible for the improved heat tolerance. This work not only expanding our understanding of microbial heat tolerance, but also emphasizing that the in vivo continuous genome mutagenesis method, GREACE, is efficient in improving microbial complex physiological trait. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  19. Genetic Segregation Analysis of a Rapeseed Dwarf Mutant

    International Nuclear Information System (INIS)

    Xiang, G.; Yu, S.; Zhang, T.; Zhao, J.; Lei, S.; Du, C.

    2016-01-01

    Dwarf resources in Brassica napus are very important for developing high-yield cultivars through dwarf-type and lodging-resistant breeding. However, few dwarf varieties have been available for this species. Here, we reported a new rapeseed dwarf mutant GRC1157, which exhibits obvious phenotypic variations on dwarf. Six generations (P /sub 1/, P/sub 1/, F/sub 1/, F/sub 1/, B/sub 1/, and B/sub 1/) were produced from a cross between dwarf mutant GRC1157 and an elite tall-type line XR16 to analyze genetic inheritances of plant height (PH), numbers of the 1st valid branch (VBN), main inflorescence length (MIL), pod numbers per main inflorescence (MPN), pod length (PL) and seed numbers per pod (PSN) using the mixed major gene plus polygene inheritance model. The genetic analysis shows different traits were controlled by different inheritance models: PH and PL by two pairs of additive-dominant-epistatic major genes plus additive-dominant-epistatic polygenes, MPN and PSN by two-pair additive-dominant-epistatic major genes plus additive-dominant polygenes, MIL by two-pair additive-dominant-epistatic major genes and VBN by one-pair additive-dominant major genes plus additive-dominant-epistatic polygenes. Furthermore, positive correlations between PH and some other traits were observed, suggesting that some traits may be co-regulated by several linkage or same loci/genes. In addition, high heritability (40.35-93.7 percent) were found for five traits (except VBN) in different segregating generations, indicating these traits were mainly affected by hereditary factors and suitable for early artificial selection. In sum, the dwarf mutant GRC1157 can serve as a valuable resource for rapeseed dwarf breeding and the genetic analysis in this study provided a foundation for further mapping and cloning dwarf genes in mutant GRC1157. (author)

  20. Genetic analysis of radiation-induced mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, R.; Wakabayashi, Y.; Niwa, O.

    2003-01-01

    Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

  1. Genetic diversity and relationship analysis of Gossypium arboreum accessions.

    Science.gov (United States)

    Liu, F; Zhou, Z L; Wang, C Y; Wang, Y H; Cai, X Y; Wang, X X; Zhang, Z S; Wang, K B

    2015-11-19

    Simple sequence repeat techniques were used to identify the genetic diversity of 101 Gossypium arboreum accessions collected from India, Vietnam, and the southwest of China (Guizhou, Guangxi, and Yunnan provinces). Twenty-six pairs of SSR primers produced a total of 103 polymorphic loci with an average of 3.96 polymorphic loci per primer. The average of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 0.59, 0.2835, and 0.4361, respectively. The diversity varied among different geographic regions. The result of principal component analysis was consistent with that of unweighted pair group method with arithmetic mean clustering analysis. The 101 G. arboreum accessions were clustered into 2 groups.

  2. Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

    Directory of Open Access Journals (Sweden)

    J R Managbanag

    Full Text Available BACKGROUND: Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein-protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of

  3. Genetic analysis of superovulatory response of Holstein cows in Canada.

    Science.gov (United States)

    Jaton, C; Koeck, A; Sargolzaei, M; Malchiodi, F; Price, C A; Schenkel, F S; Miglior, F

    2016-05-01

    Superovulation of dairy cattle is frequently used in Canada. The cost of this protocol is high, and so is the variability of the outcome. Knowing the superovulatory potential of a donor cow could influence the breeder's decision to superovulate it or not. The main objective of this study was to perform a genetic analysis for superovulatory response of Holstein cows in Canada using data recorded by Holstein Canada, and to investigate if these data could be used for genetic evaluation. Data contained the total number of embryos and the number of viable embryos from every successful flushing performed across Canada. After editing, 137,446 records of superovulation performed between 1992 and 2014 were analyzed. A univariate repeatability animal model analysis was performed for both total number of embryos and number of viable embryos. Because both data and residuals did not follow a normal distribution, records were subject to either logarithmic or Anscombe transformation. Using logarithmic transformation, heritability estimates (SE) of 0.15 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. Using Anscombe transformation, heritability estimates (SE) of 0.17 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. The genetic correlation between the 2 traits was estimated at 0.97 using logarithmic transformation and 0.95 using Anscombe transformation. Breeding values were estimated for 54,463 cows, and 3,513 sires. Only estimated breeding values of sires having a reliability higher than 40% were considered for estimated breeding values correlations with other routinely evaluated traits. The results showed that selection for a higher response to superovulation would lead to a slight decrease in milk production, but an improvement for functional traits, including all reproduction traits. In all cases, the estimated correlations are either low or modest. We conclude that

  4. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication.

    Directory of Open Access Journals (Sweden)

    Denis Avey

    2015-07-01

    Full Text Available Kaposi's Sarcoma-Associated Herpesvirus (KSHV is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK mitogen-activated protein kinase (MAPK pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass-spectrometry-based phosphoproteomic screening identified putative substrates of ORF45-activated RSK in KSHV-infected cells. Bioinformatic analyses revealed that nuclear proteins, including several transcriptional regulators, were overrepresented among these candidates. We validated the ORF45/RSK-dependent phosphorylation of several putative substrates by employing KSHV BAC mutagenesis, kinase inhibitor treatments, and/or CRISPR-mediated knockout of RSK in KSHV-infected cells. Furthermore, we assessed the consequences of knocking out these substrates on ORF45/RSK-dependent regulation of gene expression and KSHV progeny virion production. Finally, we show data to support that ORF45 regulates the translational efficiency of a subset of viral/cellular genes with complex secondary structure in their 5' UTR. Altogether, these data shed light on the mechanisms by which KSHV ORF45

  5. UV irradiation analysis of complementation between, and replication of, RNA-negative temperature-sensitivie mutants of Newcastle disease virus

    International Nuclear Information System (INIS)

    Peeples, M.E.; Bratt, M.A.

    1982-01-01

    Random uv irradiation-induced lesions destroy the infectivity of Newcastle disease virus (NDV) by blocking downstream transcription from the single viral promoter. The nucleocapsid-associated polypeptides most likely to be involved in RNA synthesis are located at the extreme ends of the genome: NP and P are promoter proximal genes, and L is the most distal gene. We attempted to order the two temperature-sensitive (ts) RNA-negative (RNA-) mutant groups of NDV by determining the uv target sizes for the complementing abilities of mutants A1 and E1. After uv irradiation, E1 was unable to complement A1, a result compatible with the A mutation lying in the L gene. In contrast, after uv irradiation A1 was able to complement E1 for both virus production and viral protein synthesis, with a target size most consistent with the E mutation lying in the P gene. UV-irradiated virus was unable to replicate as indicated by its absence in the yields of multiply infected cells, either as infectious virus or as particles with complementing activity. After irradiation, ts mutant B1ΔP, with a non-ts mutation affecting the electrophoretic mobility of the P protein, complemented E1 in a manner similar to A1, but it did not amplify the expression of ΔP in infected cells. This too is consistent with irradiated virus being unable to replicate despite the presence of the components needed for replication of E1. At high uv doses, A1 was able to complement E1 in a different, uv-resistant manner, probably by direct donation of input polypeptides. Multiplicity reactivation has previously been observed at high-multiplicity infection by uv-irradiated paramyxoviruses. In this case, virions which are noninfectious because they lack a protein component may be activated by a protein from irradiated virions

  6. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells

    DEFF Research Database (Denmark)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subf......, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology....

  7. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  8. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Therese Wilhelm

    2016-05-01

    Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

  9. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Science.gov (United States)

    Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

    2016-05-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  10. Integrative Genetic and Epigenetic Analysis Uncovers Regulatory Mechanisms of Autoimmune Disease.

    Science.gov (United States)

    Shooshtari, Parisa; Huang, Hailiang; Cotsapas, Chris

    2017-07-06

    Genome-wide association studies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk. These associations are preferentially located in non-coding DNA regions and in particular in tissue-specific DNase I hypersensitivity sites (DHSs). While these analyses clearly demonstrate the overall enrichment of disease risk alleles on gene regulatory regions, they are not designed to identify individual regulatory regions mediating risk or the genes under their control, and thus uncover the specific molecular events driving disease risk. To do so we have departed from standard practice by identifying regulatory regions which replicate across samples and connect them to the genes they control through robust re-analysis of public data. We find significant evidence of regulatory potential in 78/301 (26%) risk loci across nine autoimmune and inflammatory diseases, and we find that individual genes are targeted by these effects in 53/78 (68%) of these. Thus, we are able to generate testable mechanistic hypotheses of the molecular changes that drive disease risk. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

    Science.gov (United States)

    Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

    2016-01-01

    Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

  12. Genetic Analysis of Seed Yield Components and its Association with Forage Production in Wild and Cultivated Species of Sainfoin

    Directory of Open Access Journals (Sweden)

    A. Najafipoor

    2017-02-01

    Full Text Available Little is known about genetic variation of seed related traits and their association with forage characters in sainfoin. In order to investigate the variation and relationship among seed yield and its components, 93 genotypes from 21 wild and cultivated species of genus Onobrychis were evaluated using a randomized complete block design with four replications at Isfahan University of Technology Research Farm, Isfahan, Iran. Analysis of variance showed that there was significant difference among genotypes, indicating existence of considerable genetic variation in this germplasm. Panicle fertility and panicle length had the most variation in cultivated and the wild genotypes, respectively. Results of correlation analysis showed that seed yield was positively correlated with number of stems per plant and number of seeds per panicle and negatively correlated with panicle length and days to 50% flowering. Seed yield had positive correlation with forage yield in wild species while this correlation was not significant in cultivated one. Cluster analysis classified the genotypes into three groups which separate wild and cultivated species. Based on principal component analysis the first component was related to seed yield and the second one was related to components of forage yield which can be used for selection of high forage and seed yielding genotypes.

  13. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.

    Directory of Open Access Journals (Sweden)

    Ji'an Pan

    Full Text Available Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12 provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

  14. Sequence analysis and characterization of rolling-circle replicating plasmid pVCM01 from Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Penido, A. F. B.

    2013-12-01

    Full Text Available Aims: Characterization of cryptic plasmid pVCM01 (accession number JX133088 isolated from Salmonella enterica Enteritidis. Methodology and results: The complete sequence of pVCM01 was obtained. This plasmid possesses 1981 bp, with G+C content of 57% in agreement of the range of Salmonella genomic DNA. pVCM01 has a high degree of similarity to pB and pJ plasmids. It possesses six main open reading frames, only one have a very high degree of amino acid identity with protein involved in the rolling-circle-like replication (RCR. Based on the sequence similarities, pVCM01 plasmid belonged to the pC194/pUB110 rolling-circle replicating plasmid family. The Rep pVCM01 possesses the motifs: FLTLTVRN, HPHFHTL, SGDGYVKHERW, which were present in all Rep proteins. Conclusion, significance and impact of study: The small size of pVCM01 plasmid and its stability in E. coli cells, make it an attractive candidate to develop new vectors, such as cloning and/or expression vector.

  15. Quantitative Genetic Analysis for Yield and Yield Components in Boro Rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Supriyo CHAKRABORTY

    2010-03-01

    Full Text Available Twenty-nine genotypes of boro rice (Oryza sativa L. were grown in a randomized block design with three replications in plots of 4m x 1m with a crop geometry of 20 cm x 20 cm between November-April, in Regional Agricultural Research Station, Nagaon, India. Quantitative data were collected on five randomly selected plants of each genotype per replication for yield/plant, and six other yield components, namely plant height, panicles/plant, panicle length, effective grains/panicle, 100 grain weight and harvest index. Mean values of the characters for each genotype were used for analysis of variance and covariance to obtain information on genotypic and phenotypic correlation along with coheritability between two characters. Path analyses were carried out to estimate the direct and indirect effects of boro rice�s yield components. The objective of the study was to identify the characters that mostly influence the yield for increasing boro rice productivity through breeding program. Correlation analysis revealed significant positive genotypic correlation of yield/plant with plant height (0.21, panicles/plant (0.53, panicle length (0.53, effective grains/panicle (0.57 and harvest index (0.86. Path analysis based on genotypic correlation coefficients elucidated high positive direct effect of harvest index (0.8631, panicle length (0.2560 and 100 grain weight (0.1632 on yield/plant with a residual effect of 0.33. Plant height and panicles/plant recorded high positive indirect effect on yield/plant via harvest index whereas effective grains/panicle on yield/plant via harvest index and panicle length. Results of the present study suggested that five component characters, namely harvest index, effective grains/plant, panicle length, panicles/plant and plant height influenced the yield of boro rice. A genotype with higher magnitude of these component characters could be either selected from the existing genotypes or evolved by breeding program for genetic

  16. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  17. Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

    NARCIS (Netherlands)

    Kiryluk, Krzysztof; Li, Yifu; Sanna-Cherchi, Simone; Rohanizadegan, Mersedeh; Suzuki, Hitoshi; Eitner, Frank; Snyder, Holly J.; Choi, Murim; Hou, Ping; Scolari, Francesco; Izzi, Claudia; Gigante, Maddalena; Gesualdo, Loreto; Savoldi, Silvana; Amoroso, Antonio; Cusi, Daniele; Zamboli, Pasquale; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.; Mucha, Krzysztof; Perola, Markus; Kristiansson, Kati; Viktorin, Alexander; Magnusson, Patrik K.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Boland, Anne; Metzger, Marie; Thibaudin, Lise; Wanner, Christoph; Jager, Kitty J.; Goto, Shin; Maixnerova, Dita; Karnib, Hussein H.; Nagy, Judit; Panzer, Ulf; Xie, Jingyuan; Chen, Nan; Tesar, Vladimir; Narita, Ichiei; Berthoux, Francois; Floege, Jürgen; Stengel, Benedicte; Zhang, Hong; Lifton, Richard P.; Gharavi, Ali G.

    2012-01-01

    IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility

  18. The yeast replicative aging model.

    Science.gov (United States)

    He, Chong; Zhou, Chuankai; Kennedy, Brian K

    2018-03-08

    It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

  19. Chromatin replication and histone dynamics

    DEFF Research Database (Denmark)

    Alabert, Constance; Jasencakova, Zuzana; Groth, Anja

    2017-01-01

    Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate...... choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper...... organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure...

  20. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... The presence of sufficient genetic diversity in the germplam is an important ..... Figure 1. PCR amplification profile of Elite-II SH Wheat using the primer OPG-2. .... genetic relationships among cowpea breeding lines and local.

  1. Analysis of genetic variation in different sheep breeds using ...

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... Department of Cell Biology, Genetic Engineering Division, National Research Center, Dokki, Giza, .... polymerase chain reaction (PCR) using genomic DNA extracted ..... Technology, Egypt through the project titled "Genetic.

  2. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    restore complete fertility of a certain CMS line by various restorer lines (Tan et ... Keywords. rice; heterosis; three-way test cross; fertility restoration genetics. Journal of ..... plants indicating a strong genetic load of maintenance in. DE2. Table 8.

  3. Analysis of genetic diversity and construction of core collection of ...

    African Journals Online (AJOL)

    Jane

    2011-06-03

    Jun 3, 2011 ... Genetic diversity of 73 local mulberry varieties from Shanxi Province were screened using ISSR ... number effective of alleles, Nei's genetic diversity index and Shannon's ...... resources conservation program of the Agriculture.

  4. Comparative Analysis of Genetic Crossover Operators in Knapsack ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Knapsack problem via GA (Genetic Algorithm) is presented. We compared ... Keywords: Genetic Algorithm, Crossover, Heuristic, Arithmetic, Intermediate, Evolutionary Algorithm. The knapsack .... application to 0/1 Knapsack problem, Applied.

  5. Molecular genetic analysis of consanguineous families with primary ...

    Indian Academy of Sciences (India)

    MUZAMMIL AHMAD KHAN

    3Institute of Human Genetics, Medical University of Graz, Graz 8010, Austria. 4Department of Cell and ... Materials and methods. Family recruitment and sample collection ..... 2014 A Drosophila genetic resource of mutats to study mechanism ...

  6. Genetics researchers’ and iRB professionals’ attitudes toward genetic research review: a comparative analysis

    Science.gov (United States)

    Edwards, Karen L.; Lemke, Amy A.; Trinidad, Susan B.; Lewis, Susan M.; Starks, Helene; Snapinn, Katherine W.; Griffin, Mary Quinn; Wiesner, Georgia L.; Burke, Wylie

    2012-01-01

    Purpose Genetic research involving human participants can pose challenging questions related to ethical and regulatory standards for research oversight. However, few empirical studies describe how genetic researchers and institutional review board (IRB) professionals conceptualize ethical issues in genetic research or where common ground might exist. Methods Parallel online surveys collected information from human genetic researchers (n = 351) and IRB professionals (n = 208) regarding their views about human participant oversight for genetic protocols. Results A range of opinions were observed within groups on most issues. In both groups, a minority thought it likely that people would be harmed by participation in genetic research or identified from coded genetic data. A majority of both groups agreed that reconsent should be required for four of the six scenarios presented. Statistically significant differences were observed between groups on some issues, with more genetic researcher respondents trusting the confidentiality of coded data, fewer expecting harms from reidentification, and fewer considering reconsent necessary in certain scenarios. Conclusions The range of views observed within and between IRB and genetic researcher groups highlights the complexity and unsettled nature of many ethical issues in genome research. Our findings also identify areas where researcher and IRB views diverge and areas of common ground. PMID:22241102

  7. Genetically Modified Products in Lithuania: Situational Analysis and Consumers’ Attitudes

    OpenAIRE

    Dainora Grundey; Indre Rimkiene

    2012-01-01

    The paper analyses the genetically modified organism products (GMP) in relation to genetically modified organisms (GMO) from two perspectives: 1) from the theoretical standpoint, discussing the GMO and GMP trade conditions and 2) from the practical perspective, namely analysing the availability of GMP in the Lithuanian market. With the growing of genetically modified products (GMP) levels, it becomes important to examine the situation of genetically modified products. According to various stu...

  8. Stability analysis of delayed genetic regulatory networks with stochastic disturbances

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Qi, E-mail: zhouqilhy@yahoo.com.c [School of Automation, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China); Xu Shengyuan [School of Automation, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China); Chen Bing [Institute of Complexity Science, Qingdao University, Qingdao 266071, Shandong (China); Li Hongyi [Space Control and Inertial Technology Research Center, Harbin Institute of Technology, Harbin 150001 (China); Chu Yuming [Department of Mathematics, Huzhou Teacher' s College, Huzhou 313000, Zhejiang (China)

    2009-10-05

    This Letter considers the problem of stability analysis of a class of delayed genetic regulatory networks with stochastic disturbances. The delays are assumed to be time-varying and bounded. By utilizing Ito's differential formula and Lyapunov-Krasovskii functionals, delay-range-dependent and rate-dependent (rate-independent) stability criteria are proposed in terms of linear matrices inequalities. An important feature of the proposed results is that all the stability conditions are dependent on the upper and lower bounds of the delays. Another important feature is that the obtained stability conditions are less conservative than certain existing ones in the literature due to introducing some appropriate free-weighting matrices. A simulation example is employed to illustrate the applicability and effectiveness of the proposed methods.

  9. Genetic analysis of the cytoplasmic dynein subunit families.

    Science.gov (United States)

    Pfister, K Kevin; Shah, Paresh R; Hummerich, Holger; Russ, Andreas; Cotton, James; Annuar, Azlina Ahmad; King, Stephen M; Fisher, Elizabeth M C

    2006-01-01

    Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles.

  10. Genetic analysis of the cytoplasmic dynein subunit families.

    Directory of Open Access Journals (Sweden)

    K Kevin Pfister

    2006-01-01

    Full Text Available Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles.

  11. The genetic component of human longevity

    DEFF Research Database (Denmark)

    Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

    2018-01-01

    In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic ...

  12. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Zeggini, Eleftheria; Scott, Laura J; Saxena, Richa

    2008-01-01

    analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample......Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published...

  13. Genetic Analysis of Mice Skin Exposed by Hyper-Gravity

    Science.gov (United States)

    Takahashi, Rika; Terada, Masahiro; Seki, Masaya; Higashibata, Akira; Majima, Hideyuki J.; Ohira, Yoshinobu; Mukai, Chiaki; Ishioka, Noriaki

    2013-02-01

    In the space environment, physiological alterations, such as low bone density, muscle weakness and decreased immunity, are caused by microgravity and cosmic radiation. On the other hand, it is known that the leg muscles are hypertrophy by 2G-gravity. An understanding of the effects on human body from microgravity to hyper-gravity is very important. Recently, the Japan Aerospace Exploration Agency (JAXA) has started a project to detect the changes on gene expression and mineral metabolism caused by microgravity by analyzing the hair of astronauts who stay in the international Space Station (ISS) for a long time. From these results of human hair’s research, the genetic effects of human hair roots by microgravity will become clear. However, it is unclear how the gene expression of hair roots was effected by hypergravity. Therefore, in this experiment, we analyzed the effect on mice skin contained hair roots by comparing microgravity or hypergravity exposed mice. The purpose of this experiment is to evaluate the genetic effects on mice skin by microgravity or 2G-gravity. The samples were taken from mice exposed to space flight (FL) or hypergravity environment (2G) for 3-months, respectively. The extracted and amplified RNA from these mice skin was used to DNA microarray analysis. in this experiment, we analyzed the effect of gravity by using mice skin contained hair roots, which exposed space (FL) and hyper-gravity (2G) for 3 months and each control. By DNA microarray analysis, we found the common 98 genes changed in both FL and 2G. Among these 98 genes, the functions and pathways were identified by Gene Ontology (GO) analysis and Ingenuity Pathways Analysis (IPA) software. Next, we focused the one of the identified pathways and compared the effects on each molecules in this pathways by the different environments, such as FL and 2G. As the results, we could detect some interesting molecules, which might be depended on the gravity levels. In addition, to investigate

  14. Label-free Proteomic Analysis of Exosomes Derived from Inducible Hepatitis B Virus-Replicating HepAD38 Cell Line.

    Science.gov (United States)

    Jia, Xiaofang; Chen, Jieliang; Megger, Dominik A; Zhang, Xiaonan; Kozlowski, Maya; Zhang, Lijun; Fang, Zhong; Li, Jin; Chu, Qiaofang; Wu, Min; Li, Yaming; Sitek, Barbara; Yuan, Zhenghong

    2017-04-01

    Hepatitis B virus (HBV) infection is a major health problem worldwide. Recent evidence suggests that some viruses can manipulate the infection process by packing specific viral and cellular components into exosomes, small nanometer-sized (30-150 nm) vesicles secreted from various cells. However, the impact of HBV replication on the content of exosomes produced by hepatocytes has not been fully delineated. In this work, an HBV-inducible cell line HepAD38 was used to directly compare changes in the protein content of exosomes secreted from HepAD38 cells with or without HBV replication. Exosomes were isolated from supernantants of HepAD38 cells cultured with or without doxycycline (dox) and their purity was confirmed by transmission electron microscopy (TEM) and Western immunoblotting assays. Ion-intensity based label-free LC-MS/MS quantitation technologies were applied to analyze protein content of exosomes from HBV replicating cells [referred as HepAD38 (dox - )-exo] and from HBV nonreplicating cells [referred as HepAD38 (dox + )-exo]. A total of 1412 exosomal protein groups were identified, among which the abundance of 35 proteins was significantly changed following HBV replication. Strikingly, 5 subunit proteins from the 26S proteasome complex, including PSMC1, PSMC2, PSMD1, PSMD7 and PSMD14 were consistently enhanced in HepAD38 (dox - )-exo. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the proteasomal catabolic process. Proteasome activity assays further suggested that HepAD38 (dox - )-exo had enhanced proteolytic activity compared with HepAD38 (dox + )-exo. Furthermore, human peripheral monocytes incubated with HepAD38 (dox - )-exo induced a significantly lower level of IL-6 secretion compared with IL-6 levels from HepAD38 (dox + )-exo. Irreversible inhibition of proteasomal activity within exosomes restored higher production of IL-6 by monocytes, suggesting that transmission of

  15. Replicating MISTERS: an epidemiological criminology framework analysis of a program for criminal justice-involved minority males in the community.

    Science.gov (United States)

    Potter, Roberto Hugh; Akers, Timothy A; Bowman, Daniel Richard

    2013-01-01

    The Men in STD Training and Empowerment Research Study (MISTERS) program and epidemiological criminology began their development in Atlanta at about the same time. MISTERS focuses on men recently released from jail to reduce both HIV/STD and crime-related risk factors through a brief educational intervention. This article examines ways in which MISTERS and epidemiological criminology have been used to inform one another in the replication of the MISTERS program in Orange County, Florida. Data from 110 MISTERS participants during the first 10 months of operation are analyzed to examine the overlapping occurrence of health and criminal risk behaviors in the men's lives. This provides a test of core hypotheses from the epidemiological criminology framework. This article also examines application of the epidemiological criminology framework to develop interventions to address health and crime risk factors simultaneously in Criminal Justice-Involved populations in the community.

  16. Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.

    Science.gov (United States)

    Marchal, Claire; Sasaki, Takayo; Vera, Daniel; Wilson, Korey; Sima, Jiao; Rivera-Mulia, Juan Carlos; Trevilla-García, Claudia; Nogues, Coralin; Nafie, Ebtesam; Gilbert, David M

    2018-05-01

    This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.

  17. In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA.

    Directory of Open Access Journals (Sweden)

    Janet L Smith

    2015-05-01

    Full Text Available DnaA, the replication initiation protein in bacteria, is an AAA+ ATPase that binds and hydrolyzes ATP and exists in a heterogeneous population of ATP-DnaA and ADP-DnaA. DnaA binds cooperatively to the origin of replication and several other chromosomal regions, and functions as a transcription factor at some of these regions. We determined the binding properties of Bacillus subtilis DnaA to genomic DNA in vitro at single nucleotide resolution using in vitro DNA affinity purification and deep sequencing (IDAP-Seq. We used these data to identify 269 binding regions, refine the consensus sequence of the DnaA binding site, and compare the relative affinity of binding regions for ATP-DnaA and ADP-DnaA. Most sites had a slightly higher affinity for ATP-DnaA than ADP-DnaA, but a few had a strong preference for binding ATP-DnaA. Of the 269 sites, only the eight strongest binding ones have been observed to bind DnaA in vivo, suggesting that other cellular factors or the amount of available DnaA in vivo restricts DnaA binding to these additional sites. Conversely, we found several chromosomal regions that were bound by DnaA in vivo but not in vitro, and that the nucleoid-associated protein Rok was required for binding in vivo. Our in vitro characterization of the inherent ability of DnaA to bind the genome at single nucleotide resolution provides a backdrop for interpreting data on in vivo binding and regulation of DnaA, and is an approach that should be adaptable to many other DNA binding proteins.

  18. Genetic Code Analysis Toolkit: A novel tool to explore the coding properties of the genetic code and DNA sequences

    Science.gov (United States)

    Kraljić, K.; Strüngmann, L.; Fimmel, E.; Gumbel, M.

    2018-01-01

    The genetic code is degenerated and it is assumed that redundancy provides error detection and correction mechanisms in the translation process. However, the biological meaning of the code's structure is still under current research. This paper presents a Genetic Code Analysis Toolkit (GCAT) which provides workflows and algorithms for the analysis of the structure of nucleotide sequences. In particular, sets or sequences of codons can be transformed and tested for circularity, comma-freeness, dichotomic partitions and others. GCAT comes with a fertile editor custom-built to work with the genetic code and a batch mode for multi-sequence processing. With the ability to read FASTA files or load sequences from GenBank, the tool can be used for the mathematical and statistical analysis of existing sequence data. GCAT is Java-based and provides a plug-in concept for extensibility. Availability: Open source Homepage:http://www.gcat.bio/

  19. Analysis of genetic effects of nuclear-cytoplasmic interaction on quantitative traits: genetic model for diploid plants.

    Science.gov (United States)

    Han, Lide; Yang, Jian; Zhu, Jun

    2007-06-01

    A genetic model was proposed for simultaneously analyzing genetic effects of nuclear, cytoplasm, and nuclear-cytoplasmic interaction (NCI) as well as their genotype by environment (GE) interaction for quantitative traits of diploid plants. In the model, the NCI effects were further partitioned into additive and dominance nuclear-cytoplasmic interaction components. Mixed linear model approaches were used for statistical analysis. On the basis of diallel cross designs, Monte Carlo simulations showed that the genetic model was robust for estimating variance components under several situations without specific effects. Random genetic effects were predicted by an adjusted unbiased prediction (AUP) method. Data on four quantitative traits (boll number, lint percentage, fiber length, and micronaire) in Upland cotton (Gossypium hirsutum L.) were analyzed as a worked example to show the effectiveness of the model.

  20. The Genetic Analysis of an Acinetobacter johnsonii Clinical Strain Evidenced the Presence of Horizontal Genetic Transfer.

    Directory of Open Access Journals (Sweden)

    Sabrina Montaña

    Full Text Available Acinetobacter johnsonii rarely causes human infections. While most A. johnsonii isolates are susceptible to virtually all antibiotics, strains harboring a variety of β-lactamases have recently been described. An A. johnsonii Aj2199 clinical strain recovered from a hospital in Buenos Aires produces PER-2 and OXA-58. We decided to delve into its genome by obtaining the whole genome sequence of the Aj2199 strain. Genome comparison studies on Aj2199 revealed 240 unique genes and a close relation to strain WJ10621, isolated from the urine of a patient in China. Genomic analysis showed evidence of horizontal genetic transfer (HGT events. Forty-five insertion sequences and two intact prophages were found in addition to several resistance determinants such as blaPER-2, blaOXA-58, blaTEM-1, strA, strB, ereA, sul1, aacC2 and a new variant of blaOXA-211, called blaOXA-498. In particular, blaPER-2 and blaTEM-1 are present within the typical contexts previously described in the Enterobacteriaceae family. These results suggest that A. johnsonii actively acquires exogenous DNA from other bacterial species and concomitantly becomes a reservoir of resistance genes.

  1. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

    NARCIS (Netherlands)

    Verhoeven, Virginie J. M.; Hysi, Pirro G.; Saw, Seang-Mei; Vitart, Veronique; Mirshahi, Alireza; Guggenheim, Jeremy A.; Cotch, Mary Frances; Yamashiro, Kenji; Baird, Paul N.; Mackey, David A.; Wojciechowski, Robert; Ikram, M. Kamran; Hewitt, Alex W.; Duggal, Priya; Janmahasatian, Sarayut; Khor, Chiea-Chuen; Fan, Qiao; Zhou, Xin; Young, Terri L.; Tai, E.-Shyong; Goh, Liang-Kee; Li, Yi-Ju; Aung, Tin; Vithana, Eranga; teo, Yik-Ying; Tay, Wanting; Sim, Xueling; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Campbell, Harry; Wilson, James F.; Fleck, Brian W.; Nakata, Isao; Yoshimura, Nagahisa; Yamada, Ryo; Matsuda, Fumihiko; Ohno-Matsui, Kyoko; Nag, Abhishek; McMahon, George; St Pourcain, Beate; Lu, Yi; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Bhattacharya, Shomi; Simpson, Claire L.; Atwood, Larry D.; Li, Xiaohui; Raffel, Leslie J.; Murgia, Federico; Portas, Laura; Despriet, Dominiek D. G.; van Koolwijk, Leonieke M. E.; Wolfram, Christian; Lackner, Karl J.; Tönjes, Anke; Mägi, Reedik; Lehtimäki, Terho; Kähönen, Mika; Esko, Tõnu; Metspalu, Andres; Rantanen, Taina; Pärssinen, Olavi; Klein, Barbara E.; Meitinger, Thomas; Spector, Timothy D.; Oostra, Ben A.; Smith, Albert V.; de Jong, Paulus T. V. M.; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Eiríksdóttir, Guðný; Gudnason, Vilmundur; Döring, Angela; Bettecken, Thomas; Uitterlinden, André G.; Williams, Cathy; Zeller, Tanja; Castagné, Raphaële; Oexle, Konrad; van Duijn, Cornelia M.; Iyengar, Sudha K.; Mitchell, Paul; Wang, Jie Jin; Höhn, René; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Stambolian, Dwight; Wong, Tien-Yin; Hammond, Christopher J.; Klaver, Caroline C. W.

    2012-01-01

    Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis

  2. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells.

    Science.gov (United States)

    Hummon, Amanda B; Pitt, Jason J; Camps, Jordi; Emons, Georg; Skube, Susan B; Huppi, Konrad; Jones, Tamara L; Beissbarth, Tim; Kramer, Frank; Grade, Marian; Difilippantonio, Michael J; Ried, Thomas; Caplen, Natasha J

    2012-01-04

    Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/ß-catenin pathway. We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH.

  3. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  4. A replicated association between polymorphisms near TNFα and risk for adverse reactions to radiotherapy

    Science.gov (United States)

    Talbot, C J; Tanteles, G A; Barnett, G C; Burnet, N G; Chang-Claude, J; Coles, C E; Davidson, S; Dunning, A M; Mills, J; Murray, R J S; Popanda, O; Seibold, P; West, C M L; Yarnold, J R; Symonds, R P

    2012-01-01

    Background: Response to radiotherapy varies between individuals both in terms of efficacy and adverse reactions. Finding genetic determinants of radiation response would allow the tailoring of the treatment, either by altering the radiation dose or by surgery. Despite a growing number of studies in radiogenomics, there are no well-replicated genetic association results. Methods: We carried out a candidate gene association study and replicated the result using three additional large cohorts, a total of 2036 women scored for adverse reactions to radiotherapy for breast cancer. Results: Genetic variation near the tumour necrosis factor alpha gene is shown to affect several clinical endpoints including breast induration, telangiectasia and overall toxicity. In the combined analysis homozygosity for the rare allele increases overall toxicity (P=0.001) and chance of being in the upper quartile of risk with odds ratio of 2.46 (95% confidence interval 1.52–3.98). Conclusion: We have identified that alleles of the class III major histocompatibility complex region associate with overall radiotherapy toxicity in breast cancer patients by using internal replication through a staged design. This is the first well-replicated report of a genetic predictor for radiotherapy reactions. PMID:22767148

  5. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  6. Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges

    Science.gov (United States)

    Marangi, Giuseppe; Traynor, Bryan J.

    2018-01-01

    The genetic architecture of amyotrophic lateral sclerosis (ALS) is being increasingly understood. In this far-reaching review, we examine what is currently known about ALS genetics and how these genes were initially identified. We also discuss the various types of mutations that might underlie this fatal neurodegenerative condition and outline some of the strategies that might be useful in untangling them. These include expansions of short repeat sequences, common and low-frequency genetic variations, de novo mutations, epigenetic changes, somatic mutations, epistasis, oligogenic and polygenic hypotheses. PMID:25316630

  7. Feature selection using genetic algorithms for fetal heart rate analysis

    International Nuclear Information System (INIS)

    Xu, Liang; Redman, Christopher W G; Georgieva, Antoniya; Payne, Stephen J

    2014-01-01

    The fetal heart rate (FHR) is monitored on a paper strip (cardiotocogram) during labour to assess fetal health. If necessary, clinicians can intervene and assist with a prompt delivery of the baby. Data-driven computerized FHR analysis could help clinicians in the decision-making process. However, selecting the best computerized FHR features that relate to labour outcome is a pressing research problem. The objective of this study is to apply genetic algorithms (GA) as a feature selection method to select the best feature subset from 64 FHR features and to integrate these best features to recognize unfavourable FHR patterns. The GA was trained on 404 cases and tested on 106 cases (both balanced datasets) using three classifiers, respectively. Regularization methods and backward selection were used to optimize the GA. Reasonable classification performance is shown on the testing set for the best feature subset (Cohen's kappa values of 0.45 to 0.49 using different classifiers). This is, to our knowledge, the first time that a feature selection method for FHR analysis has been developed on a database of this size. This study indicates that different FHR features, when integrated, can show good performance in predicting labour outcome. It also gives the importance of each feature, which will be a valuable reference point for further studies. (paper)

  8. Clinical features and genetic analysis of tuberous sclerosis pedigrees

    Directory of Open Access Journals (Sweden)

    LI Ya-qin

    2012-06-01

    Full Text Available Objective In order to understand tuberous sclerosis complex better, the clinical manifestation, imaging characteristics, and genetic characteristics of tuberous sclerosis complex from 3 pedigrees were investigated. Methods The clinical data of patients from 3 tuberous sclerosis families were collected. The gene mutation type of TSC2 of proband in pedigree one was determined by PCR and direct gene sequencing. Results All of the 3 probands went to our clinic for the reason of epilepsy. Brain imaging examination noted intracranial nodular calcification. EEG showed comprehensive spines and slow waves, sharp waves. The pedigree 1 has family history, two male patients and 3 female patients, all had facial angiofibromas and epilepsy. Gene mutation analysis of TSC2 demonstrated the c.1444-2A > C mutation in index patient. All the 3 index patients had mental retardation, autism and hypopigmented macule. Conclusion For infants and young children with epilepsy as the first symptom, accompanied by mental retardation, autism, facial angiofibromas or hypopigmented macule and other skin abnormalities, brain imaging examination noted intracranial nodular calcification are highly suggestive of tuberous sclerosis complex. TSC1 and TSC2 gene analysis contribute to the diagnosis of this disease, genentic counseling and prenatal diagnosis.

  9. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

    Directory of Open Access Journals (Sweden)

    Lingjun Zuo

    2016-11-01

    Full Text Available It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs play important roles in nicotine dependence (ND and influence the number of cigarettes smoked per day (CPD in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4. These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.

  10. Genetic analysis of field and physiological indicators of drought ...

    African Journals Online (AJOL)

    In order to study the inheritance of field, physiological and metabolite indicators of drought tolerance in wheat, an eight-parental diallel cross, excluding reciprocals, was grown in a randomized complete block design (RCBD) with three replications under two different water regimes (irrigated and rainfed). Significant ...

  11. quantitative genetic analysis of total glucosinolate, oil and protein ...

    African Journals Online (AJOL)

    ADMIN

    were field-tested in a randomized block design at two locations in Ethiopia. Seeds were ... complete block design with two replications. The plot size ...... Sci. 56:10–14. 35. Underhill, E.W. (1980). Glucosinolates. In: Secondary. Plant Products, pp. 493–511, (Bell, E.A. and. Charlwood, B.V., eds). Springler, Berlin. 36. Utz, H.F. ...

  12. A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: replication of genetic linkage on chromosome 5q11.2-q14.3.

    Science.gov (United States)

    Allen, Elsie M; Hsueh, Wen-Chi; Sabra, Mona M; Pollin, Toni I; Ladenson, Paul W; Silver, Kristi D; Mitchell, Braxton D; Shuldiner, Alan R

    2003-03-01

    Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P Amish.

  13. Analysis of the genetic basis of disease in the context of worldwide human relationships and migration.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    2013-05-01

    Full Text Available Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

  14. Genetic analysis of three South African horse breeds

    Directory of Open Access Journals (Sweden)

    E.G. Cothran

    1998-07-01

    Full Text Available Genetic variability at 7 blood-group and 10 biochemical genetic loci was examined in 3 South African horse breeds, the Nooitgedacht, Boerperd and Basuto Pony. Observed heterozygosity for these breeds was intermediate for domestic horses, with the highest heterozygosity in the Boerperd and the lowest in the Basuto Pony. The 3 breeds show greater genetic similarity to each other than to other domestic horse breeds. Compared to other breeds, the South African breeds show greater genetic similarity to breeds such as the Thoroughbred, Holstein, Trakehner and Hanovarian and also to North American breeds such as the Saddlebred, Standardbred and Morgan Horse.

  15. Genetic stability evaluation of quercus suber l. somatic embryogenesis by rapd analysis

    International Nuclear Information System (INIS)

    Fernandes, P.; Costa, A.; Rocha, A.C.C.; Santos, C.

    2011-01-01

    A reliable protocol for adult Quercus suber L. somatic embryogenesis (SE) was developed recently. To evaluate the potential use of this protocol in cork oak forest breeding programs, it is essential to guarantee somatic embryos/emblings genetic stability. Random Amplification of Polymorphic DNA (RAPD) is currently used to assess somaclonal variation providing information on genetic variability of the micropropagation process. In this work, SE was induced from adult trees by growing leaf explants on MS medium supplemented with 2,4-D and zeatin. Embling conversion took place on MS medium without growth regulators. DNA from donor tree, somatic embryos and emblings was used to assess genetic variability by RAPD fingerprinting. Fourteen primers produced 165 genetic loci with high quality and reproducibility. Despite somatic embryos originated some poor quality PCR-profiles, replicable and excellent fingerprints were obtained for both donor plant and embling. Results presented no differences among regenerated emblings and donor plant. Hence, the SE protocol used did not induce, up to moment, any genetic variability, confirming data previously obtained with other molecular/genetic techniques, supporting that this protocol may be used to provide true-to-type plants from important forestry species. (author)

  16. Who Needs Replication?

    Science.gov (United States)

    Porte, Graeme

    2013-01-01

    In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…

  17. Molecular Mechanisms of DNA Replication Checkpoint Activation

    Directory of Open Access Journals (Sweden)

    Bénédicte Recolin

    2014-03-01

    Full Text Available The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.

  18. Genetic diversity analysis and conservation of the Chinese herb ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... Salvia miltiorrhiza is an economically important floral herb. However, little work has been conducted to further our understanding of the genetics of this herb. In this study, a representative set of germplasm of. S. miltiorrhiza populations was used to analyze genetic diversity using amplified fragment length.

  19. An existential analysis of genetic engineering and human rights ...

    African Journals Online (AJOL)

    Genetic engineering for purposes of human enhancement poses risks that justify regulation. However, this paper argues philosophically that it is inappropriate to use human rights treaties to prohibit germ-line genetic engineering whether therapeutic or for purposes of enhancement. When also looked at existentially, the ...

  20. Genetic analysis of seed proteins contents in cowpea ( Vigna ...

    African Journals Online (AJOL)

    In order to select cowpea genotypes with high food value, 10 varieties were genetically screened in Ngaoundéré (Cameroon) for seed crude protein and its soluble fractions contents. Five divergent lines were studied through a 5 x 5 half diallel cross mating. The genotypes presented a significant genetic variability for these ...

  1. A roadmap for the genetic analysis of renal aging

    NARCIS (Netherlands)

    Noordmans, Gerda A.; van Goor, Harry; Hillebrands, Jan-Luuk; Korstanje, Ron

    2015-01-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this

  2. Genetic diversity analysis in the Hypericum perforatum populations ...

    African Journals Online (AJOL)

    Assessment of genetic variability among the Hypericum perforatum populations is critical to the development of effective conservation strategies in the Kashmir valley. To obtain accurate estimates of genetic diversity among and within populations of H. perforatum, inter-simple sequence repeats (ISSR) markers were used.

  3. Genetic diversity of Najdi sheep based on microsatellite analysis ...

    African Journals Online (AJOL)

    The prime objective of this research was to measure the genetic polymorphism of main sheep breed of Saudi Arabia, Najdi. Randomly selected 49 blood samples were used to extract the DNA followed by polymerase chain reaction (PCR), using 19 microsatellite markers, which were used to investigate the genetic ...

  4. Genetic diversity analysis and conservation of the Chinese herb ...

    African Journals Online (AJOL)

    Salvia miltiorrhiza is an economically important floral herb. However, little work has been conducted to further our understanding of the genetics of this herb. In this study, a representative set of germplasm of. S. miltiorrhiza populations was used to analyze genetic diversity using amplified fragment length polymorphism ...

  5. Genetic diversity analysis of rice cultivars from various origins using ...

    African Journals Online (AJOL)

    Genetic diversity is of paramount importance for the success of any plant breeding program. An experiment was conducted to assess the extent of genetic diversity and similarity of 24 rice cultivars from various origins using 29 simple sequence repeat (SSR) markers. A total of 144 alleles were detected at the 29 SSR primer ...

  6. A quantitative genetic analysis of intermediate asthma phenotypes

    DEFF Research Database (Denmark)

    Thomsen, S.F.; Ferreira, M.A.R.; Kyvik, K.O.

    2009-01-01

    to the observed data using maximum likelihood methods. RESULTS: Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most......AIM: To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE). METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from...... substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (rhoA) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (rhoE) = -0.46, and between FeNO and airway...

  7. A quantitative genetic analysis of intermediate asthma phenotypes

    DEFF Research Database (Denmark)

    Thomsen, S F; Ferreira, M A R; Kyvik, K O

    2009-01-01

    to the observed data using maximum likelihood methods. Results: Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most......Aim: To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE). Methods: Within a sampling frame of 21 162 twin subjects, 20-49 years of age, from...... substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (rho(A)) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (rho(E)) = -0.46, and between FeNO and airway...

  8. Genetic variation analysis of the Bali street dog using microsatellites

    Directory of Open Access Journals (Sweden)

    Wilton Alan N

    2005-02-01

    Full Text Available Abstract Background Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships. Results The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis. Conclusions This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time.

  9. Molecular genetic analysis of phosphomannomutase genes in Triticum monococcum

    Institute of Scientific and Technical Information of China (English)

    Chunmei; Yu; Xinyan; Liu; Qian; Zhang; Xinyu; He; Wan; Huai; Baohua; Wang; Yunying; Cao; Rong; Zhou

    2015-01-01

    In higher plants, phosphomannomutase(PMM) is essential for synthesizing the antioxidant ascorbic acid through the Smirnoff–Wheeler pathway. Previously, we characterized six PMM genes(Ta PMM-A1, A2, B1, B2, D1 and D2) in common wheat(Triticum aestivum, AABBDD).Here, we report a molecular genetic analysis of PMM genes in Triticum monococcum(AmAm), a diploid wheat species whose Amgenome is closely related to the A genome of common wheat. Two distinct PMM genes, Tm PMM-1 and Tm PMM-2, were found in T. monococcum. The coding region of Tm PMM-1 was intact and highly conserved. In contrast, two main Tm PMM-2 alleles were identified, with Tm PMM-2a possessing an intact coding sequence and Tm PMM-2b being a pseudogene. The transcript level of Tm PMM-2a was much higher than that of Tm PMM-2b, and a bacterially expressed Tm PMM-2a recombinant protein displayed relatively high PMM activity. In general, the total transcript level of PMM was substantially higher in accessions carrying Tm PMM-1 and Tm PMM-2a than those harboring Tm PMM-1 and Tm PMM-2b. However, total PMM protein and activity levels did not differ drastically between the two genotypes. This work provides new information on PMM genes in T. monococcum and expands our understanding on Triticeae PMM genes, which may aid further functional and applied studies of PMM in crop plants.

  10. Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing.

    Directory of Open Access Journals (Sweden)

    Lance D Eckerle

    2010-05-01

    Full Text Available Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN in nonstructural protein 14 (nsp14 of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication

  11. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes

    DEFF Research Database (Denmark)

    Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H

    2014-01-01

    . In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs......) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications...... for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies....

  12. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    A. Dessa Sadovnick

    2016-07-01

    Full Text Available Multiple sclerosis (MS is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D in plasminogen (PLG as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351 in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117, despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87. To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.

  13. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

    Science.gov (United States)

    Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles

    2016-01-01

    Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

  14. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    Science.gov (United States)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  15. Genetic diagnosis in Hemophilia A from southern China: five novel mutations and one preimplantation genetic analysis.

    Science.gov (United States)

    Chen, J; Wang, J; Lin, X Y; Xu, Y W; He, Z H; Li, H Y; Chen, S Q; Jiang, W Y

    2017-04-01

    As there is currently no complete cure for hemophilia A (HA), the identification of pathogenic mutations in factor VIII (FVIII) gene from HA patients and carriers, which can contribute to genetic counseling prenatal diagnosis, and preimplantation genetic diagnosis (PGD), is an important step to prevent HA. A total of 14 unrelated Chinese HA subjects (FVIII activity C, c.304_305insA, c.1594T>A, c.6045G>A, and c.2645_2646insG) were found. The real-time PCR showed that the expression of FVIII mRNAs was lower in HA patients than in normal subjects. Prenatal diagnosis and PGD were successfully performed: Two of three fetuses and four of eight blastomeres were confirmed to be normal. In conclusion, genetic diagnosis of 14 unrelated HA subjects, 20 carrier subjects, three fetuses, and one PGD was successfully performed in our study. © 2016 John Wiley & Sons Ltd.

  16. Diagnostic and therapeutic implications of genetic heterogeneity in myeloid neoplasms uncovered by comprehensive mutational analysis

    Directory of Open Access Journals (Sweden)

    Sarah M. Choi

    2017-01-01

    Full Text Available While growing use of comprehensive mutational analysis has led to the discovery of innumerable genetic alterations associated with various myeloid neoplasms, the under-recognized phenomenon of genetic heterogeneity within such neoplasms creates a potential for diagnostic confusion. Here, we describe two cases where expanded mutational testing led to amendment of an initial diagnosis of chronic myelogenous leukemia with subsequent altered treatment of each patient. We demonstrate the power of comprehensive testing in ensuring appropriate classification of genetically heterogeneous neoplasms, and emphasize thoughtful analysis of molecular and genetic data as an essential component of diagnosis and management.

  17. Preimplantation genetic diagnosis for mitochondrial DNA mutations: analysis of one blastomere suffices.

    Science.gov (United States)

    Sallevelt, Suzanne C E H; Dreesen, Joseph C F M; Coonen, Edith; Paulussen, Aimee D C; Hellebrekers, Debby M E I; de Die-Smulders, Christine E M; Smeets, Hubert J M; Lindsey, Patrick

    2017-10-01

    Preimplantation genetic diagnosis (PGD) is a reproductive strategy for mitochondrial DNA (mtDNA) mutation carriers, strongly reducing their risk of affected offspring. Embryos either without the mutation or with mutation load below the phenotypic threshold are transferred to the uterus. Because of incidental heteroplasmy deviations in single blastomere and the relatively limited data available, we so far preferred relying on two blastomeres rather than one. Considering the negative effect of a two-blastomere biopsy protocol compared with a single-blastomere biopsy protocol on live birth delivery rate, we re-evaluated the error rate in our current dataset. For the m.3243A>G mutation, sufficient embryos/blastomeres were available for a powerful analysis. The diagnostic error rate, defined as a potential false-negative result, based on a threshold of 15%, was determined in 294 single blastomeres analysed in 73 embryos of 9 female m.3243A>G mutation carriers. Only one out of 294 single blastomeres (0.34%) would have resulted in a false-negative diagnosis. False-positive diagnoses were not detected. Our findings support a single-blastomere biopsy PGD protocol for the m.3243A>G mutation as the diagnostic error rate is very low. As in the early preimplantation embryo no mtDNA replication seems to occur and the mtDNA is divided randomly among the daughter cells, we conclude this result to be independent of the specific mutation and therefore applicable to all mtDNA mutations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses.

    Science.gov (United States)

    Lauber, Chris; Gorbalenya, Alexander E

    2012-04-01

    Virus taxonomy has received little attention from the research community despite its broad relevance. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3890-3904, 2012), we have introduced a quantitative approach to hierarchically classify viruses of a family using pairwise evolutionary distances (PEDs) as a measure of genetic divergence. When applied to the six most conserved proteins of the Picornaviridae, it clustered 1,234 genome sequences in groups at three hierarchical levels (to which we refer as the "GENETIC classification"). In this study, we compare the GENETIC classification with the expert-based picornavirus taxonomy and outline differences in the underlying frameworks regarding the relation of virus groups and genetic diversity that represent, respectively, the structure and content of a classification. To facilitate the analysis, we introduce two novel diagrams. The first connects the genetic diversity of taxa to both the PED distribution and the phylogeny of picornaviruses. The second depicts a classification and the accommodated genetic diversity in a standardized manner. Generally, we found striking agreement between the two classifications on species and genus taxa. A few disagreements concern the species Human rhinovirus A and Human rhinovirus C and the genus Aphthovirus, which were split in the GENETIC classification. Furthermore, we propose a new supergenus level and universal, level-specific PED thresholds, not reached yet by many taxa. Since the species threshold is approached mostly by taxa with large sampling sizes and those infecting multiple hosts, it may represent an upper limit on divergence, beyond which homologous recombination in the six most conserved genes between two picornaviruses might not give viable progeny.

  19. Genetic analysis of maternal ability in Iberian pigs.

    Science.gov (United States)

    Rodriguez, C; Rodrigañez, J; Silio, L

    1994-01-12

    A practical measure of milk yield of the sow is the weight of the litter at three weeks of age when the piglet growth is entirely dependent on the milking ability of the dam. Genetic parameters of litter size at birth (LS) and litter weight at 21 days (LW21) were estimated using a DFREML procedure from records of 4883 litters (2,049 for LW21) of Iberian breed. Preliminary analysis showed negligible maternal genetic effects. The model for both traits included the fixed effects of farrowing period (86 levels), parity (6) and inbreeding coefficients of dam (Fd) and litter (F(1) ) as co-variables, and three random effects-additive genetic value, permanent environmental effect and residual on both traits. Heritability and repeatability estimates were 0.064 and 0.126 (LS) and 0.163 and 0.270 (LW21) respectively. Estimated genetic and phenotypic correlations were 0.214 and 0.043. The inbreeding depression per 10 % increase of Fd or F(1) was -0.150 or -0.170 in live piglets and -0.983 or -1.023 kg of litter weight. When the model for LW21 included the dam inbreeding and the number of suckling piglets as co-variables, the heritability and repeatability estimates were 0.243 and 0.431 respectively. A complementary analysis was carried out on individual records (weight at 21 days) of 26206 piglets farrowed by 1317 sows. The model included the fixed effects of sex, farrowing period, parity, and the inbreeding coefficients of dam and individual, as co-variables. A total of four random effects were also included: direct and maternal genetic effects, common environmental effects and residual. Estimates of heritability, maternal heritability and common environmental coefficient were, respectively, 0.019, 0.163 and 0.128, reinforcing the evidence of genetic variance for milk producing ability in Iberian sows. The estimated values of inbreeding depression for piglet weight at 21 days were -0.072 and -0.098 kg per 10 % increase in dam or litter inbreeding. ZUSAMMENFASSUNG: Genetische

  20. Simulation Approach for Timing Analysis of Genetic Logic Circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2017-01-01

    in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior...... of single and cascaded genetic logic circuits. We further analyze the timing sensitivity of circuits by varying the degradation rates and concentrations. Our approach can be used not only to characterize the timing behavior but also to analyze the timing constraints of cascaded genetic logic circuits...

  1. Low-dose DNA damage and replication stress responses quantified by optimized automated single-cell image analysis

    DEFF Research Database (Denmark)

    Mistrik, Martin; Oplustilova, Lenka; Lukas, Jiri

    2009-01-01

    sensitive, quantitative, rapid and simple fluorescence image analysis in thousands of adherent cells per day. Sensitive DNA breakage estimation through analysis of phosphorylated histone H2AX (gamma-H2AX), and homologous recombination (HR) assessed by a new RPA/Rad51 dual-marker approach illustrate...

  2. Molecular genetic analysis of consanguineous families with primary ...

    Indian Academy of Sciences (India)

    RESEARCH NOTE Volume 96 Issue 2 June 2017 pp 383-387 ... Autosomal recessive primary microcephaly is a rare genetic disorder that is ... Department of Cell and Developmental Biology, School of Life Sciences, University of Science and ...

  3. Genetic diversity analysis of Labeo gonius (Hamilton, 1822) in three ...

    African Journals Online (AJOL)

    a

    2013-05-08

    May 8, 2013 ... tool to characterize population-level genetic variation in various fish species ... rise to protein variants called allozymes that differ slightly in electric charges. ..... Black Sea Coast. Acta zool. Bulg. ... Inc., Florida, USA. 350 pp.

  4. Analysis of genetic diversity in Arrhenatherum elatius Germplasm ...

    African Journals Online (AJOL)

    Jane

    2011-07-25

    Jul 25, 2011 ... The genetic diversity of 19 Arrhenatherum elatius accessions was analyzed ... can be used as novel DNA markers for genomic .... phylogenies and evolutionary biology. .... struction Project of the Beijing Academy of Agriculture.

  5. Genetic diversity analysis in the Hypericum perforatum populations ...

    African Journals Online (AJOL)

    user

    2014-01-01

    Jan 1, 2014 ... 2Cancer Genetics Lab, Department of Biochemistry, Maulana Azad Medical College and Associated ... sciatica and depression (Ghasemi et al., 2013; Barnes et .... environmental factors for each sampling site were also.

  6. Molecular-genetic analysis of two cases with retinoblastoma ...

    Indian Academy of Sciences (India)

    Unknown

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of ... to chromosomal deletion, single-nucleotide alteration, microdeletion, loss ... informed consent of the parent.

  7. Smoking and caffeine consumption: a genetic analysis of their association

    NARCIS (Netherlands)

    Treur, J.L.; Taylor, A.E.; Ware, J.J.; Nivard, M.G.; Neale, M.C.; McMahon, G.; Hottenga, J.J.; Baselmans, B.M.L.; Boomsma, D.I.; Munafò, M.; Vink, J.M.

    2017-01-01

    Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine.

  8. Analysis of genetic diversity in chickpea ( Cicer arietinum L ...

    African Journals Online (AJOL)

    Genetic diversity of seven chickpea (Cicer arietinum L.) cultivars of Pakistani origin ... effective method to determine the variations among the chickpea cultivars. ... to broaden the germplasm base in the future for chickpea breeding programs.

  9. Analysis of genetic diversity and estimation of inbreeding coefficient ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-01-18

    Jan 18, 2010 ... Key words: Genetic diversity, microsatellite markers, Caspian horse breed. INTRODUCTION ... heterozygosity, observed and effective number of alleles at each ... computer program version 1.31 (Yeh et al., 1999). Based on ...

  10. Killer Whale Genetic Data - Southern resident killer whale pedigree analysis

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In this project, we are using genetic variation to infer mating patterns in the southern killer whale community. In Canada, this population was listed as threatened...

  11. Genetic diversity analysis of various red spider mite- resistant ...

    African Journals Online (AJOL)

    User

    2011-05-02

    May 2, 2011 ... 3Key Laboratory of Plant Breeding and Genetics, Sichuan Agricultural University, Ya'an, 625014, P. R. ... Random amplified polymorphic DNA (RAPD) is a DNA ..... spider mite-resistant, bumper, high-quality and disease-.

  12. Genetic Analysis of Micro-environmental Plasticity in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Morgante, Fabio; Sorensen, Daniel A; Sørensen, Peter

    Quantitative genetic models recognize the potential for genotype by environment interaction, whereby different genotypes have different plastic responses to changes in macro-environmental conditions. Recently, it has been recognized that micro-environmental plasticity (‘residual’ variance) may also...... be genetically variable. This study utilized the Drosophila Genetic Reference Panel (DGRP) to accurately estimate the genetic variance of micro-environmental plasticity for chill coma recovery time and startle response. Estimates of broad sense heritabilities for both traits are substantial (from 0.51 to 0.......77), of the same order as the heritability at the level of the trait mean for startle response and even larger for chill coma recovery. Genome wide association analyses identified molecular variants (from 15 to 31 depending on the sex and the trait) associated with micro-environmental plasticity. These findings...

  13. Gregor Mendel's Genetic Experiments: A Statistical Analysis after 150 Years

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan

    2016-01-01

    Roč. 12, č. 2 (2016), s. 20-26 ISSN 1801-5603 Institutional support: RVO:67985807 Keywords : genetics * history of science * biostatistics * design of experiments Subject RIV: BB - Applied Statistics, Operational Research

  14. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    Directory of Open Access Journals (Sweden)

    Cancare Fabio

    2009-07-01

    performance while leaving the CPU available for other tasks. The GPU workstation containing three GPUs costs $2000 while obtaining similar performance on a Beowulf cluster requires 150 CPU cores which, including the added infrastructure and support cost of the cluster system, cost approximately $82,500. Conclusion Graphics hardware based computing provides a cost effective means to perform genetic analysis of epistasis using MDR on large datasets without the infrastructure of a computing cluster.

  15. Accelerating epistasis analysis in human genetics with consumer graphics hardware.

    Science.gov (United States)

    Sinnott-Armstrong, Nicholas A; Greene, Casey S; Cancare, Fabio; Moore, Jason H

    2009-07-24

    tasks. The GPU workstation containing three GPUs costs $2000 while obtaining similar performance on a Beowulf cluster requires 150 CPU cores which, including the added infrastructure and support cost of the cluster system, cost approximately $82,500. Graphics hardware based computing provides a cost effective means to perform genetic analysis of epistasis using MDR on large datasets without the infrastructure of a computing cluster.

  16. Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase.

    Directory of Open Access Journals (Sweden)

    Amnon Koren

    2010-08-01

    Full Text Available Eukaryotic centromeres are maintained at specific chromosomal sites over many generations. In the budding yeast Saccharomyces cerevisiae, centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function; whereas, in most other eukaryotes, centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role. Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA. By determining the genome-wide replication timing program of the C. albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. Importantly, epigenetic formation of new ectopic centromeres (neocentromeres was accompanied by shifts in replication timing, such that a neocentromere became the first to replicate and became associated with origin recognition complex (ORC components. Furthermore, changing the level of the centromere-specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions, further supporting the idea that centromere proteins determine origin activity. Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. This strand-biased pattern is conserved, together with centromere position, among related strains and species, in a manner independent of primary DNA sequence. Thus, inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time. We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position.

  17. Systems genetic analysis of brown adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Saba, L. M.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Smith, H.; Tabakoff, B.

    2018-01-01

    Roč. 50, č. 1 (2018), s. 52-66 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * coexpression modules * quantitative trait locus * recombinant inbred strains * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Human genetics Impact factor: 3.044, year: 2016

  18. Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

    Science.gov (United States)

    Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R

    2015-08-01

    The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.

  19. The replication recipe : What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  20. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  1. Multivariate analysis in a genetic divergence study of Psidium guajava.

    Science.gov (United States)

    Nogueira, A M; Ferreira, M F S; Guilhen, J H S; Ferreira, A

    2014-12-18

    The family Myrtaceae is widespread in the Atlantic Forest and is well-represented in the Espírito Santo State in Brazil. In the genus Psidium of this family, guava (Psidium guajava L.) is the most economically important species. Guava is widely cultivated in tropical and subtropical countries; however, the widespread cultivation of only a small number of guava tree cultivars may cause the genetic vulnerability of this crop, making the search for promising genotypes in natural populations important for breeding programs and conservation. In this study, the genetic diversity of 66 guava trees sampled in the southern region of Espírito Santo and in Caparaó, MG, Brazil were evaluated. A total of 28 morphological descriptors (11 quantitative and 17 multicategorical) and 18 microsatellite markers were used. Principal component, discriminant and cluster analyses, descriptive analyses, and genetic diversity analyses using simple sequence repeats were performed. Discrimination of accessions using molecular markers resulted in clustering of genotypes of the same origin, which was not observed using morphological data. Genetic diversity was detected between and within the localities evaluated, regardless of the methodology used. Genetic differentiation among the populations using morphological and molecular data indicated the importance of the study area for species conservation, genetic erosion estimation, and exploitation in breeding programs.

  2. What Should Researchers Expect When They Replicate Studies? A Statistical View of Replicability in Psychological Science.

    Science.gov (United States)

    Patil, Prasad; Peng, Roger D; Leek, Jeffrey T

    2016-07-01

    A recent study of the replicability of key psychological findings is a major contribution toward understanding the human side of the scientific process. Despite the careful and nuanced analysis reported, the simple narrative disseminated by the mass, social, and scientific media was that in only 36% of the studies were the original results replicated. In the current study, however, we showed that 77% of the replication effect sizes reported were within a 95% prediction interval calculated using the original effect size. Our analysis suggests two critical issues in understanding replication of psychological studies. First, researchers' intuitive expectations for what a replication should show do not always match with statistical estimates of replication. Second, when the results of original studies are very imprecise, they create wide prediction intervals-and a broad range of replication effects that are consistent with the original estimates. This may lead to effects that replicate successfully, in that replication results are consistent with statistical expectations, but do not provide much information about the size (or existence) of the true effect. In this light, the results of the Reproducibility Project: Psychology can be viewed as statistically consistent with what one might expect when performing a large-scale replication experiment. © The Author(s) 2016.

  3. Genetic and genomic analysis of RNases in model cyanobacteria.

    Science.gov (United States)

    Cameron, Jeffrey C; Gordon, Gina C; Pfleger, Brian F

    2015-10-01

    Cyanobacteria are diverse photosynthetic microbes with the ability to convert CO2 into useful products. However, metabolic engineering of cyanobacteria remains challenging because of the limited resources for modifying the expression of endogenous and exogenous biochemical pathways. Fine-tuned control of protein production will be critical to optimize the biological conversion of CO2 into desirable molecules. Messenger RNAs (mRNAs) are labile intermediates that play critical roles in determining the translation rate and steady-state protein concentrations in the cell. The majority of studies on mRNA turnover have focused on the model heterotrophic bacteria Escherichia coli and Bacillus subtilis. These studies have elucidated many RNA modifying and processing enzymes and have highlighted the differences between these Gram-negative and Gram-positive bacteria, respectively. In contrast, much less is known about mRNA turnover in cyanobacteria. We generated a compendium of the major ribonucleases (RNases) and provide an in-depth analysis of RNase III-like enzymes in commonly studied and diverse cyanobacteria. Furthermore, using targeted gene deletion, we genetically dissected the RNases in Synechococcus sp. PCC 7002, one of the fastest growing and industrially attractive cyanobacterial strains. We found that all three cyanobacterial homologs of RNase III and a member of the RNase II/R family are not essential under standard laboratory conditions, while homologs of RNase E/G, RNase J1/J2, PNPase, and a different member of the RNase II/R family appear to be essential for growth. This work will enhance our understanding of native control of gene expression and will facilitate the development of an RNA-based toolkit for metabolic engineering in cyanobacteria.

  4. Development of Pineapple Microsatellite Markers and Germplasm Genetic Diversity Analysis

    Directory of Open Access Journals (Sweden)

    Suping Feng

    2013-01-01

    Full Text Available Two methods were used to develop pineapple microsatellite markers. Genomic library-based SSR development: using selectively amplified microsatellite assay, 86 sequences were generated from pineapple genomic library. 91 (96.8% of the 94 Simple Sequence Repeat (SSR loci were dinucleotide repeats (39 AC/GT repeats and 52 GA/TC repeats, accounting for 42.9% and 57.1%, resp., and the other three were mononucleotide repeats. Thirty-six pairs of SSR primers were designed; 24 of them generated clear bands of expected sizes, and 13 of them showed polymorphism. EST-based SSR development: 5659 pineapple EST sequences obtained from NCBI were analyzed; among 1397 nonredundant EST sequences, 843 were found containing 1110 SSR loci (217 of them contained more than one SSR locus. Frequency of SSRs in pineapple EST sequences is 1SSR/3.73 kb, and 44 types were found. Mononucleotide, dinucleotide, and trinucleotide repeats dominate, accounting for 95.6% in total. AG/CT and AGC/GCT were the dominant type of dinucleotide and trinucleotide repeats, accounting for 83.5% and 24.1%, respectively. Thirty pairs of primers were designed for each of randomly selected 30 sequences; 26 of them generated clear and reproducible bands, and 22 of them showed polymorphism. Eighteen pairs of primers obtained by the one or the other of the two methods above that showed polymorphism were selected to carry out germplasm genetic diversity analysis for 48 breeds of pineapple; similarity coefficients of these breeds were between 0.59 and 1.00, and they can be divided into four groups accordingly. Amplification products of five SSR markers were extracted and sequenced, corresponding repeat loci were found and locus mutations are mainly in copy number of repeats and base mutations in the flanking region.

  5. Development of Pineapple Microsatellite Markers and Germplasm Genetic Diversity Analysis

    Science.gov (United States)

    Tong, Helin; Chen, You; Wang, Jingyi; Chen, Yeyuan; Sun, Guangming; He, Junhu; Wu, Yaoting

    2013-01-01

    Two methods were used to develop pineapple microsatellite markers. Genomic library-based SSR development: using selectively amplified microsatellite assay, 86 sequences were generated from pineapple genomic library. 91 (96.8%) of the 94 Simple Sequence Repeat (SSR) loci were dinucleotide repeats (39 AC/GT repeats and 52 GA/TC repeats, accounting for 42.9% and 57.1%, resp.), and the other three were mononucleotide repeats. Thirty-six pairs of SSR primers were designed; 24 of them generated clear bands of expected sizes, and 13 of them showed polymorphism. EST-based SSR development: 5659 pineapple EST sequences obtained from NCBI were analyzed; among 1397 nonredundant EST sequences, 843 were found containing 1110 SSR loci (217 of them contained more than one SSR locus). Frequency of SSRs in pineapple EST sequences is 1SSR/3.73 kb, and 44 types were found. Mononucleotide, dinucleotide, and trinucleotide repeats dominate, accounting for 95.6% in total. AG/CT and AGC/GCT were the dominant type of dinucleotide and trinucleotide repeats, accounting for 83.5% and 24.1%, respectively. Thirty pairs of primers were designed for each of randomly selected 30 sequences; 26 of them generated clear and reproducible bands, and 22 of them showed polymorphism. Eighteen pairs of primers obtained by the one or the other of the two methods above that showed polymorphism were selected to carry out germplasm genetic diversity analysis for 48 breeds of pineapple; similarity coefficients of these breeds were between 0.59 and 1.00, and they can be divided into four groups accordingly. Amplification products of five SSR markers were extracted and sequenced, corresponding repeat loci were found and locus mutations are mainly in copy number of repeats and base mutations in the flanking region. PMID:24024187

  6. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  7. Chromatin Immunoprecipitation of Replication Factors Moving with the Replication Fork

    OpenAIRE

    Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi

    2009-01-01

    Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...

  8. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  9. Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

    Science.gov (United States)

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

    The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

  10. Analysis of genetic polymorphism of nine short tandem repeat loci in ...

    African Journals Online (AJOL)

    Yomi

    2012-03-15

    Mar 15, 2012 ... Key words: short tandem repeat, repeat motif, genetic polymorphism, Han population, forensic genetics. INTRODUCTION. Short tandem repeat (STR) is widely .... Data analysis. The exact test of Hardy-Weinberg equilibrium was conducted with. Arlequin version 3.5 software (Computational and Molecular.

  11. Analysis of genetic diversity of Piper spp. in Hainan Island (China ...

    African Journals Online (AJOL)

    Inter-simple sequence repeat (ISSR) analysis was used to evaluate the genetic variation of Piper spp. from Hainan, China. 247 polymorphic bands out of a total of 248 (99.60%) were generated from 74 individual plants of Piper spp. The overall level of genetic diversity among Piper spp. in Hainan was high, with the mean ...

  12. Analysis of the Threat of Genetically Modified Organisms for Biological Warfare

    Science.gov (United States)

    2011-05-01

    biological warfare. The primary focus of the framework are those aspects of the technology directly affecting humans by inducing virulent infectious disease...applications. Simple organisms such as fruit flies have been used to study the effects of genetic changes across generations. Transgenic mice are...Analysis * Multi-cell pathogens * Toxins (Chemical products of living cells.) * Fungi (Robust organism; no genetic manipulation needed

  13. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    International Nuclear Information System (INIS)

    Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

  14. Genetic Diversity and Relationships of Neolamarckia cadamba (Roxb. Bosser progenies through cluster analysis

    Directory of Open Access Journals (Sweden)

    M. Preethi Shree

    2018-04-01

    Full Text Available Genetic diversity analysis was conducted for biometric attributes in 20 progenies of Neolamarckia cadamba. The application of D2 clustering technique in Neolamarckia cadamba genetic resources resolved the 20 progenies into five clusters. The maximum intra cluster distance was shown by the cluster II. The maximum inter cluster distance was recorded between cluster III and V which indicated the presence of wider genetic distance between Neolamarckia cadamba progenies. Among the growth attributes, volume (36.84 % contributed maximum towards genetic divergence followed by bole height, basal diameter, tree height, number of branches in Neolamarckia cadamba progenies.

  15. Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China

    Directory of Open Access Journals (Sweden)

    Haihua Bai

    2015-01-01

    Full Text Available The large scale genome wide association studies (GWAS have identified approximately 80 single nucleotide polymorphisms (SNPs conferring susceptibility to type 2 diabetes (T2D. However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1, rs1531343 (HMGA2, rs8042680 (PRC1, rs7578597 (THADA, rs1333051 (CDKN2, rs6723108 (TMEM163, rs163182 and rs2237897 (KCNQ1, rs1387153 (MTNR1B, rs243021 (BCL11A, and rs10229583 (PAX4 in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1, is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163 whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations.

  16. Microsatellite marker analysis of the genetic variability in Hanoverian Hounds.

    Science.gov (United States)

    Lüpke, L; Distl, O

    2005-04-01

    Genetic variability of the dog breed Hanoverian Hound was analysed using a set of 16 microsatellites. The sample of 92 dogs was representative for the total current population [n=334, inbreeding coefficient 9.2%, relationship coefficient 11.2%] with respect to the level and distribution of the inbreeding and relationship coefficients. All microsatellites used were in Hardy-Weinberg equilibrium. The average number of alleles was 6.4. The average observed heterozygosity (H(O)) was slightly higher than the expected heterozygosity (H(E)). Dinucleotide microsatellites exhibited lower polymorphism information content (PIC) than tetranucleotide microsatellites (0.52 versus 0.66). The average PIC was 0.61. The individual inbreeding coefficient was negatively related to the average H(O) of all microsatellites, whereas the proportion of genes from introducing of Hanoverian Hounds from abroad showed no relationships to H(O). We found that the genetic variability in the Hanoverian Hounds analysed here was unexpectedly higher than that previously published for dog breeds of similar population size. Even in dog breeds of larger population size heterogyzosity was seldom higher than that observed here. The rather high genetic variability as quantified by polymorphic microsatellites in Hanoverian Hounds may be due to a large genetic variation in the founder animals of this breed and to the fact that this genetic diversity could be maintained despite genetic bottlenecks experienced by this breed in the 1920s and 1950s and despite the presence of high inbreeding and relationship coefficients for more than 50 years.

  17. Genetic Analysis of Pinus sylvestris L. and Pinus sylvestris forma turfosa L. Using RAPD Markers

    Directory of Open Access Journals (Sweden)

    Beáta ÁBRAHÁM

    2010-03-01

    Full Text Available The purpose of the present study was to determine the level of genetic diversity within and among Ciuc basin, Romania (populations from Mohos and Luci raised bogs in Harghita Mountain and Sumuleu in Ciuc Mountain Pinus sylvestris populations using molecular markers. Two of populations (Mohos and Luci seems to be the descendants that survived the continental glaciation. Genetic diversity was analyzed by RAPD (Random Amplified Polymorphic DNA. Nine primers were selected for analysis, which generated reproducible bands. On base of presence or absence of homologues bands Nei’s gene diversity, the percentage of polymorphic loci and Nei’s unbiased genetic distance were calculated. The level of genetic variation among populations was found to be low. For both populations the variation values among populations were higher than within populations. The fossil records and geological historical data explain the extremely low genetic diversity of this species. Pinus sylvestris experienced strong bottlenecks during its evolutionary history, which caused the loss of genetic variation. Genetic drift and breeding in post-bottlenecked small populations may be the major forces that contribute to low genetic diversity and genetic differentiation of populations. Human activities may have accelerated the loss of genetic diversity in Pinus sylvestris.

  18. Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

    DEFF Research Database (Denmark)

    Madsen, Majbritt Busk; Kogelman, L J A; Kadarmideen, H N

    2016-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the in...... genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.The Pharmacogenomics Journal advance online publication, 18 October 2016; doi:10.1038/tpj.2016.68....

  19. A forward-genetic screen and dynamic analysis of lambda phage host-dependencies reveals an extensive interaction network and a new anti-viral strategy.

    Directory of Open Access Journals (Sweden)

    Nathaniel D Maynard

    2010-07-01

    Full Text Available Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli genes--over half of which have not been previously associated with infection--that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation-one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles.

  20. Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank.

    Science.gov (United States)

    Cortes, Adrian; Dendrou, Calliope A; Motyer, Allan; Jostins, Luke; Vukcevic, Damjan; Dilthey, Alexander; Donnelly, Peter; Leslie, Stephen; Fugger, Lars; McVean, Gil

    2017-09-01

    Genetic discovery from the multitude of phenotypes extractable from routine healthcare data can transform understanding of the human phenome and accelerate progress toward precision medicine. However, a critical question when analyzing high-dimensional and heterogeneous data is how best to interrogate increasingly specific subphenotypes while retaining statistical power to detect genetic associations. Here we develop and employ a new Bayesian analysis framework that exploits the hierarchical structure of diagnosis classifications to analyze genetic variants against UK Biobank disease phenotypes derived from self-reporting and hospital episode statistics. Our method displays a more than 20% increase in power to detect genetic effects over other approaches and identifies new associations between classical human leukocyte antigen (HLA) alleles and common immune-mediated diseases (IMDs). By applying the approach to genetic risk scores (GRSs), we show the extent of genetic sharing among IMDs and expose differences in disease perception or diagnosis with potential clinical implications.

  1. Genetic origin and dispersal of the invasive soybean aphid inferred from population genetic analysis and approximate Bayesian computation.

    Science.gov (United States)

    Fang, Fang; Chen, Jing; Jiang, Li-Yun; Qu, Yan-Hua; Qiao, Ge-Xia

    2018-01-09

    Biological invasion is considered one of the most important global environmental problems. Knowledge of the source and dispersal routes of invasion could facilitate the eradication and control of invasive species. Soybean aphid, Aphis glycines Matsumura, is one of the most destructive soybean pests. For effective management of this pest, we conducted genetic analyses and approximate Bayesian computation (ABC) analysis to determine the origins and dispersal of the aphid species, as well as the source of its invasion in the USA, using eight microsatellite loci and the mitochondrial cytochrome c oxidase subunit I (COI) gene. We were able to identify a significant isolation by distance (IBD) pattern and three genetic lineages in the microsatellite data but not in the mtDNA dataset. The genetic structure showed that the USA population has the closest relationship with those from Korea and Japan, indicating that the two latter populations might be the sources of the invasion to the USA. Both population genetic analyses and ABC showed that the northeastern populations in China were the possible sources of the further spread of A. glycines to Indonesia. The dispersal history of this aphid can provide useful information for pest management strategies and can further help predict areas at risk of invasion. This article is protected by copyright. All rights reserved.

  2. Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

    Directory of Open Access Journals (Sweden)

    Gerda A Noordmans

    Full Text Available Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4. Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97, NZW(0.41, NON(0.30, B10(0.21, C3 H(0.9 and C57BR(0.7. The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.

  3. Genetic analysis reveals diversity and genetic relationship among Trichoderma isolates from potting media, cultivated soil and uncultivated soil.

    Science.gov (United States)

    Al-Sadi, Abdullah M; Al-Oweisi, Fatma A; Edwards, Simon G; Al-Nadabi, Hamed; Al-Fahdi, Ahmed M

    2015-07-28

    Trichoderma is one of the most common fungi in soil. However, little information is available concerning the diversity of Trichoderma in soil with no previous history of cultivation. This study was conducted to investigate the most common species and the level of genetic relatedness of Trichoderma species from uncultivated soil in relation to cultivated soil and potting media. A total of 24, 15 and 13 Trichoderma isolates were recovered from 84 potting media samples, 45 cultivated soil samples and 65 uncultivated soil samples, respectively. Analysis based on the internal transcribed spacer region of the ribosomal RNA (rRNA) and the translation elongation factor gene (EF1) indicated the presence of 9 Trichoderma species: T. harzianum (16 isolates), T. asperellum (13), T. citrinoviride (9), T. orientalis (3), T. ghanense (3), T. hamatum (3), T. longibrachiatum (2), T. atroviride (2), and T. viride (1). All species were found to occur in potting media samples, while five Trichoderma species were recovered from the cultivated soils and four from the uncultivated soils. AFLP analysis of the 52 Trichoderma isolates produced 52 genotypes and 993 polymorphic loci. Low to moderate levels of genetic diversity were found within populations of Trichoderma species (H = 0.0780 to 0.2208). Analysis of Molecular Variance indicated the presence of very low levels of genetic differentiation (Fst = 0.0002 to 0.0139) among populations of the same Trichoderma species obtained from the potting media, cultivated soil and uncultivated soil. The study provides evidence for occurrence of Trichoderma isolates in soil with no previous history of cultivation. The lack of genetic differentiation among Trichoderma populations from potting media, cultivated soil and uncultivated soil suggests that some factors could have been responsible for moving Trichoderma propagules among the three substrates. The study reports for the first time the presence of 4 Trichoderma species in Oman: T

  4. Genetic analysis of maternal and paternal lineages in Kabardian ...

    African Journals Online (AJOL)

    The high mitochondrial and also remarkable paternal diversity of the Kabardian horse is caused by its long history with a widely spread maternal origin and the introduction of Arabian as well as Thoroughbred influenced stallions for improvement. This high genetic diversity provides a good situation for the ongoing breed ...

  5. Analysis of the genetic diversity of four rabbit genotypes using ...

    African Journals Online (AJOL)

    Dr.Ola

    2013-05-15

    May 15, 2013 ... diseases or market conditions. A considerable number of genetic diversity studies for several livestock species have been carried out during recent years by research. *Corresponding author. E-mail: ola.galal@agr.kfs.edu.eg or olagalal2002@yahoo.com , Tel/Fax: +2-0479102930. Abbreviations: APRI ...

  6. Historical analysis of Newfoundland dog fur colour genetics ...

    African Journals Online (AJOL)

    Whereas small white marks on the chest and/or paw appears to be a random event, the historical data supports the existence of an 'Irish spotted' fur colour pattern, with white head blaze, breast, paws and tail tip, in spotted/spotted homozygotes. Keywords: Fur colour genetics, Irish spotting, Landseer Newfoundland, MITF, ...

  7. genetic analysis of yield and flesh colour in sweetpotato abstract ...

    African Journals Online (AJOL)

    ACSS

    2016-02-26

    Feb 26, 2016 ... The Jaccard's similarity coefficient indicated moderate to low genetic similarity distances ... of the parental genotypes enables more effective choice of parents in breeding improved varieties. ... alone has reported that 43.6% of children between 1 .... Field evaluation. ..... The reciprocal and maternal effects.

  8. Genetic analysis of body weight of Takifugu rubripes at different ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2016-11-09

    Nov 9, 2016 ... 3Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, China .... During the larval-culture period, water ... The measured values at time t were conditioned on measured values at time t – 1. Thus, the conditional genetic model can be written as follows (Zhu, 1995; Atchley ...

  9. Evaluation of schistosome promoter expression for transgenesis and genetic analysis.

    Directory of Open Access Journals (Sweden)

    Shuang Liang

    Full Text Available Schistosome worms of the genus Schistosoma are the causative agents of schistosomiasis, a devastating parasitic disease affecting more than 240 million people worldwide. Schistosomes have complex life cycles, and have been challenging to manipulate genetically due to the dearth of molecular tools. Although the use of gene overexpression, gene knockouts or knockdowns are straight-forward genetic tools applied in many model systems, gene misexpression and genetic manipulation of schistosome genes in vivo has been exceptionally challenging, and plasmid based transfection inducing gene expression is limited. We recently reported the use of polyethyleneimine (PEI as a simple and effective method for schistosome transfection and gene expression. Here, we use PEI-mediated schistosome plasmid transgenesis to define and compare gene expression profiles from endogenous and nonendogenous promoters in the schistosomula stage of schistosomes that are potentially useful to misexpress (underexpress or overexpress gene product levels. In addition, we overexpress schistosome genes in vivo using a strong promoter and show plasmid-based misregulation of genes in schistosomes, producing a clear and distinct phenotype--death. These data focus on the schistosomula stage, but they foreshadow strong potential for genetic characterization of schistosome molecular pathways, and potential for use in overexpression screens and drug resistance studies in schistosomes using plasmid-based gene expression.

  10. DNA methylation and genetic diversity analysis of genus Cycas in ...

    African Journals Online (AJOL)

    mallory

    2012-01-12

    Jan 12, 2012 ... elucidate the role of epigenetics in the genetic diversity of these plants. MATERIALS AND METHODS. Plant materials and DNA extraction. 66 Cycas samples consisting of 10 species and one subspecies were collected from the Nong Nooch Tropical Garden, Chonburi province, Thailand. For each species ...

  11. Genetic analysis of wild apple resources in Shandong province ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... Apple (malus domestica Borkh.), which is a widely cultivated, important and economic fruit crop with nutritive and medicinal importance, has emerged as a model horticultural crop in this post-genomic era. Wild apple resources are important and they develop gradually in apple industry and genetic diversity.

  12. Genetic analysis of wild apple resources in Shandong province ...

    African Journals Online (AJOL)

    Apple (malus domestica Borkh.), which is a widely cultivated, important and economic fruit crop with nutritive and medicinal importance, has emerged as a model horticultural crop in this post-genomic era. Wild apple resources are important and they develop gradually in apple industry and genetic diversity. In this study, two ...

  13. Genetic analysis of cardiovascular risk factor clustering in spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Kostka, Vlastimil; Musilová, Alena; Kazdová, L.; Fučíková, A.; Křenová, D.; Bílá, V.; Křen, Vladimír

    2000-01-01

    Roč. 46, - (2000), s. 233-240 ISSN 0015-5497 R&D Projects: GA MŠk LN00A079; GA ČR GA305/00/1646; GA ČR GA301/00/1636; GA MZd NB4904 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.667, year: 2000

  14. Analysis of genetic relationships of mulberry ( Morus L. ) germplasm ...

    African Journals Online (AJOL)

    ... bands and 6.9 bands per primer combination. Mean gene diversity and PIC were 0.1611 and 0.1353, respectively. The genetic similarity coefficient ranged from 0.6905 to 0.9524, with an average of 0.8330. The phylogenetic tree was obtained using the UPGMA method using the total number of amplified SRAP fragments.

  15. Analysis of genetic structure of white croaker using amplified ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-09-15

    Sep 15, 2009 ... the genetic differentiation of P. argentata between China and Japan coastal waters. ... revealed that white croaker might choose the retention larval strategy within .... extension of 7 min at 72°C. PCR products were run on 6.0%.

  16. Simple sequence repeat (SSR) markers analysis of genetic diversity ...

    African Journals Online (AJOL)

    hope&shola

    2012-04-24

    Apr 24, 2012 ... erucic acid in the oil and low glucosinolate content in the meal has made rapeseed a valuable source of high quality oil for people and nutritional protein for live-stock. (Qiu et al., 2006). Previous studies have demonstrated that yellow seeds have a thinner seed coat than black seeds in the same genetic ...

  17. Analysis of genetic diversity in Eucalyptus grandis (Hill ex Maiden ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... repeats (ISSR) molecular markers ... significant genetic variation between seed sources with 26.4%, (Gst = 0.264) of the total variation attributed to ... 20 μl consisting of 10 mM Tris-HCL pH 9.0, 50 mM KCl, 0.1% Triton. X-100 ...

  18. Genetic variability, correlation and path analysis in sponge gourd ...

    African Journals Online (AJOL)

    Windows-7

    2013-02-06

    Feb 6, 2013 ... fiber used in industries for filter and cleaning the motor car, glass wares, kitchen ... The fibrous vascular system inside the fruit after been separated from the skin, ... was carried out to gather information on genetic variability ...

  19. Analysis of genetic variation in different banana ( Musa species ...

    African Journals Online (AJOL)

    The banana (Musa acuminata Colla) is considered as an important crop plant due to its high economic value as good dietary source. Here, we analyze the genetic relationship of four different banana varieties that are cultivated in south India. Random amplified polymorphic DNAs (RAPDs) fingerprinting of these banana ...

  20. Genetic diversity analysis of mustard (Brassica spp.) germplasm ...

    African Journals Online (AJOL)

    sunny t

    successfully cultivated between Aman and Boro rice rotation without affecting this popular cropping pattern. So, it is urgent to analyze the genetic diversity and its response for the selection of short duration mustard genotypes for increasing our cropping intensity. Diversity at marker loci is currently the most feasible strategy ...

  1. AFLP analysis of genetic diversity in main cultivated strains of ...

    African Journals Online (AJOL)

    Ganoderma mushroom is one of the most prescribed traditional medicines, which has been used for medicinal purposes for centuries particularly in China, Japan, Korea and other Asian countries. In this article, the different strains of Ganoderma spp. used in production and their genetic relations of the closely related strains ...

  2. Pushing the envelope in genetic analysis of species invasion

    Science.gov (United States)

    Samuel A. Cushman

    2015-01-01

    How a species spreads once introduced into a new environment is a major question in landscape genetics. When the species in question is a potential disease vector, the findings are important not only for fundamental science, but can impact applied science and public health as well. In this issue of Molecular Ecology Medley et al. (2014) study, the invasion...

  3. RAPD analysis for genetic diversity of two populations of Mystus ...

    African Journals Online (AJOL)

    ) was applied to analyze the genetic variation of the 2 populations of Mystus vittatus (Bloch) of Madhya Pradesh, India. 10 random 10-mer primers were primarily scored in 3 individuals from each of the 2 locations. Five primers, which gave ...

  4. Preliminary molecular analysis of the genetic diversity of some ...

    African Journals Online (AJOL)

    In the arid and semi arid areas, salt bush (Atriplex) represents an important forage resource. The characterization of the genetic diversity of these species is useful for their classification, their conservation and their improvement. In this context, we used the random amplified polymorphic DNA-polymerase chain reaction ...

  5. Genetic analysis of wild and cultivated germplasm of pigeonpea ...

    African Journals Online (AJOL)

    To compare the efficiency of the use of single versus multiple markers, the genetic diversity was quantified among 12 diverse pigeonpea germplasm comprised of eight wild and four cultivated using both random amplified polymorphic DNA (RAPD) and simple sequence repeat (SSR) markers, and how well these two types ...

  6. Analysis of Genetic diversity and reltionships in local Tunisian barley ...

    African Journals Online (AJOL)

    Yomi

    tools in the characterization and evaluation of genetic diversity within and between species and populations. It has been shown that different markers might reveal different classes of variation (Powell et al., 1996; Russell et al., 1997). It is correlated with the genome fraction surveyed by each kind of marker, their distribution ...

  7. Analysis of genetic variation of inducible nitric oxide synthase and ...

    African Journals Online (AJOL)

    The genetic diversity of 100 Malaysian native chickens was investigated using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) for two candidate genes: inducible nitric oxide synthase (INOS) and natural resistance-associated macrophage protein 1 (NRAMP1). The two genes were selected ...

  8. Microsatellite analysis of the genetic relationships between wild

    Indian Academy of Sciences (India)

    In the present study, we isolated 11 microsatellite DNA markers, and analysed the genetic diversity and differentiation between cultured stocks and wild populations of the giant grouper originating from the South China Sea. A total of 390 alleles at 11 microsatellite loci were detected in 130 individuals from five different ...

  9. Analysis of genetic diversity and construction of core collection of ...

    African Journals Online (AJOL)

    Jane

    2011-06-03

    Jun 3, 2011 ... Genetic diversity of 73 local mulberry varieties from Shanxi Province were screened using ISSR markers, with l5 primers combinations selected for their reproducibility and polymorphism. 129 bands were amplified, of which 115 bands showed polymorphism and the ratio of polymorphism bands was.

  10. Molecular genetic analysis of the Chinese Erhualian pig breed | Yue ...

    African Journals Online (AJOL)

    The Chinese Erhualian is one of the most prolific pig breeds in the world, but it is in danger of being replaced by other exotic pig breeds because of its slow growth rate and high fat content in the body. To obtain some genetic information for conservation, we analysed the Erhualian pigs by using a PCR-RFLP for the ...

  11. 1 Hierarchical Approaches to the Analysis of Genetic Diversity in ...

    African Journals Online (AJOL)

    2015-04-14

    Apr 14, 2015 ... Study of genetic diversity is the process by which variation ... diversity tree is available, a core collection can be selected by .... are numerous natural factors, such as hybridization and clinical .... to develop a deeper understanding of the topic .... This can be detected by southern hybridization after running ...

  12. Genetic analysis of floating Enteromorpha prolifera in the Yellow Sea with AFLP marker

    Science.gov (United States)

    Liu, Cui; Zhang, Jing; Sun, Xiaoyu; Li, Jian; Zhang, Xi; Liu, Tao

    2011-09-01

    Extremely large accumulation of green algae Enteromorpha prolifera floated along China' coastal region of the Yellow Sea ever since the summer of 2008. Amplified Fragment Length Polymorphism (AFLP) analysis was applied to assess the genetic diversity and relationships among E. prolifera samples collected from 9 affected areas of the Yellow Sea. Two hundred reproducible fragments were generated with 8 AFLP primer combinations, of which 194 (97%) were polymorphic. The average Nei's genetic diversity, the coefficiency of genetic differentiation (Gst), and the average gene flow estimated from Gst in the 9 populations were 0.4018, 0.6404 and 0.2807 respectively. Cluster analysis based on the unweighed pair group method with arithmetic averages (UPGMA) showed that the genetic relationships within one population or among different populations were all related to their collecting locations and sampling time. Large genetic differentiation was detected among the populations. The E. prolifera originated from different areas and were undergoing a course of mixing.

  13. A better coefficient of determination for genetic profile analysis.

    Science.gov (United States)

    Lee, Sang Hong; Goddard, Michael E; Wray, Naomi R; Visscher, Peter M

    2012-04-01

    Genome-wide association studies have facilitated the construction of risk predictors for disease from multiple Single Nucleotide Polymorphism markers. The ability of such "genetic profiles" to predict outcome is usually quantified in an independent data set. Coefficients of determination (R(2) ) have been a useful measure to quantify the goodness-of-fit of the genetic profile. Various pseudo-R(2) measures for binary responses have been proposed. However, there is no standard or consensus measure because the concept of residual variance is not easily defined on the observed probability scale. Unlike other nongenetic predictors such as environmental exposure, there is prior information on genetic predictors because for most traits there are estimates of the proportion of variation in risk in the population due to all genetic factors, the heritability. It is this useful ability to benchmark that makes the choice of a measure of goodness-of-fit in genetic profiling different from that of nongenetic predictors. In this study, we use a liability threshold model to establish the relationship between the observed probability scale and underlying liability scale in measuring R(2) for binary responses. We show that currently used R(2) measures are difficult to interpret, biased by ascertainment, and not comparable to heritability. We suggest a novel and globally standard measure of R(2) that is interpretable on the liability scale. Furthermore, even when using ascertained case-control studies that are typical in human disease studies, we can obtain an R(2) measure on the liability scale that can be compared directly to heritability. © 2012 Wiley Periodicals, Inc.

  14. Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis.

    Science.gov (United States)

    Ishioka, Kuka; Masaoka, Hiroyuki; Ito, Hidemi; Oze, Isao; Ito, Seiji; Tajika, Masahiro; Shimizu, Yasuhiro; Niwa, Yasumasa; Nakamura, Shigeo; Matsuo, Keitaro

    2018-04-03

    Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (P interaction  = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.

  15. Analysis of genetic relationships of pearl millet (Pennisetum glaucum L.) landraces from Zimbabwe, using microsatellites

    CSIR Research Space (South Africa)

    Chakauya, E

    2008-01-01

    Full Text Available and indigenous farmer given names. Analysis was done by PAGE stained with ethidium bromide. Simple matching coefficients were compared and the genetic relationships between genotypes were clarified on dendrograms by unweighted pair-group averages (UPGMA). Two...

  16. Sparse redundancy analysis of high-dimensional genetic and genomic data

    NARCIS (Netherlands)

    Csala, Attila; Voorbraak, Frans P. J. M.; Zwinderman, Aeilko H.; Hof, Michel H.

    2017-01-01

    Motivation: Recent technological developments have enabled the possibility of genetic and genomic integrated data analysis approaches, where multiple omics datasets from various biological levels are combined and used to describe (disease) phenotypic variations. The main goal is to explain and

  17. Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into Rhp51 independent homologous recombination

    DEFF Research Database (Denmark)

    Vejrup-Hansen, Rasmus; Mizuno, Ken'Ichi; Miyabe, Izumi

    2011-01-01

    -like protein, Rtt101/Cul8, a potential paralog of Cullin 4. We performed epistasis analysis between ¿mms1 and mutants of pathways with known functions in genome integrity, and measured the recruitment of homologous recombination proteins to blocked replication forks and recombination frequencies. We show that......-specific replication fork barrier and that, in a ¿mms1 strain, Rad22(Rad52) and RPA recruitment to blocked forks are reduced, whereas Rhp51 recruitment is unaffected. In addition, Mms1 appears to specifically promote chromosomal rearrangements in a recombination assay. These observations suggest that Mms1 acts...... is particularly important when a single strand break is converted into a double strand break during replication. Genetic data connect Mms1 to a Mus81 and Rad22(Rad52) dependent, but Rhp51 independent, branch of homologous recombination. This is supported by results demonstrating that Mms1 is recruited to a site...

  18. Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene.

    Science.gov (United States)

    Chintalapudi, Sumana R; Jablonski, Monica M

    2017-01-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

  19. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Hummon Amanda B

    2012-01-01

    Full Text Available Abstract Background Colorectal carcinomas (CRC carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH, a protein recently linked to regulation of the AKT1/ß-catenin pathway. Conclusions We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of

  20. Genetic association analysis of LARS2 with type 2 diabetes

    DEFF Research Database (Denmark)

    Reiling, E; Jafar-Mohammadi, B; van 't Riet, E

    2010-01-01

    was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk. METHODS: We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch...... individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we...... of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility....

  1. Study on characteristic points of boiling curve by using wavelet analysis and genetic algorithm

    International Nuclear Information System (INIS)

    Wei Huiming; Su Guanghui; Qiu Suizheng; Yang Xingbo

    2009-01-01

    Based on the wavelet analysis theory of signal singularity detection,the critical heat flux (CHF) and minimum film boiling starting point (q min ) of boiling curves can be detected and analyzed by using the wavelet multi-resolution analysis. To predict the CHF in engineering, empirical relations were obtained based on genetic algorithm. The results of wavelet detection and genetic algorithm prediction are consistent with experimental data very well. (authors)

  2. A novel genetic tool for clonal analysis of fourth chromosome mutations

    OpenAIRE

    Sousa-Neves, Rui; Schinaman, Joseph M.

    2012-01-01

    The fourth chromosome of Drosophila remains one of the most intractable regions of the fly genome to genetic analysis. The main difficulty posed to the genetic analyses of mutations on this chromosome arises from the fact that it does not undergo meiotic recombination, which makes recombination mapping impossible, and also prevents clonal analysis of mutations, a technique which relies on recombination to introduce the prerequisite recessive markers and FLP-recombinase recognition targets (FR...

  3. Comparative analysis of phenotypes features in two common genetic variants of limb-girdle muscular dystrophy

    Directory of Open Access Journals (Sweden)

    I. V. Sharkova

    2015-01-01

    Full Text Available The algorithm of differential diagnosis of the two most common genetic variants the limb-girdle muscular dystrophy (LGMD2A and DMD, developed on the basis of a comprehensive survey of 85 patients with a diagnosis specification using techniques of DNA analysis. It is shown that the accurate diagnosis of LGMD genetic types should be based on the results of the clinical and genealogical, biochemical and molecular genetic analysis. The proposed algorithm will significantly reduces the economic and time costs with expensive DNA testing.

  4. Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms

    Directory of Open Access Journals (Sweden)

    Arehart Eric

    2009-03-01

    Full Text Available Abstract Background The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation. Results We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194. We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI database (n = 29967 and a control set of sequences (coding region not associated with SNP sites randomly selected from the NCBI database (n = 29967. We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level of p ≤ 0.05. Significant models (p Conclusion The present study represents the first use of this computational methodology for modeling nonlinear patterns in molecular genetics. MDR was able to identify distinct nucleotide patterning around sites of mutations dependent upon the observed nucleotide change. We discovered one flanking region set that included five nucleotides clustered around a specific type of SNP site. Based on the strongly associated patterns identified in

  5. DNA replication stress and cancer chemotherapy.

    Science.gov (United States)

    Kitao, Hiroyuki; Iimori, Makoto; Kataoka, Yuki; Wakasa, Takeshi; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

    2018-02-01

    DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. A landscape genetic analysis of important agricultural pest species in Tunisia: The whitefly Bemisia tabaci.

    Directory of Open Access Journals (Sweden)

    Ahmed Ben Abdelkrim

    Full Text Available Combining landscape ecology and genetics provides an excellent framework to appreciate pest population dynamics and dispersal. The genetic architectures of many species are always shaped by environmental constraints. Because little is known about the ecological and genetic traits of Tunisian whitefly populations, the main objective of this work is to highlight patterns of biodiversity, genetic structure and migration routes of this pest. We used nuclear microsatellite loci to analyze B. tabaci populations collected from various agricultural areas across the country and we determine their biotype status. Molecular data were subsequently interpreted in an ecological context supplied from a species distribution model to infer habitat suitability and hereafter the potential connection paths between sampling localities. An analysis of landscape resistance to B. tabaci genetic flow was thus applied to take into account habitat suitability, genetic relatedness and functional connectivity of habitats within a varied landscape matrix. We shed light on the occurrence of three geographically delineated genetic groups with high levels of genetic differentiation within each of them. Potential migration corridors of this pest were then established providing significant advances toward the understanding of genetic features and the dynamic dispersal of this pest. This study supports the hypothesis of a long-distance dispersal of B. tabaci followed by infrequent long-term isolations. The Inference of population sources and colonization routes is critical for the design and implementation of accurate management strategies against this pest.

  7. A landscape genetic analysis of important agricultural pest species in Tunisia: The whitefly Bemisia tabaci.

    Science.gov (United States)

    Ben Abdelkrim, Ahmed; Hattab, Tarek; Fakhfakh, Hatem; Belkadhi, Mohamed Sadok; Gorsane, Faten

    2017-01-01

    Combining landscape ecology and genetics provides an excellent framework to appreciate pest population dynamics and dispersal. The genetic architectures of many species are always shaped by environmental constraints. Because little is known about the ecological and genetic traits of Tunisian whitefly populations, the main objective of this work is to highlight patterns of biodiversity, genetic structure and migration routes of this pest. We used nuclear microsatellite loci to analyze B. tabaci populations collected from various agricultural areas across the country and we determine their biotype status. Molecular data were subsequently interpreted in an ecological context supplied from a species distribution model to infer habitat suitability and hereafter the potential connection paths between sampling localities. An analysis of landscape resistance to B. tabaci genetic flow was thus applied to take into account habitat suitability, genetic relatedness and functional connectivity of habitats within a varied landscape matrix. We shed light on the occurrence of three geographically delineated genetic groups with high levels of genetic differentiation within each of them. Potential migration corridors of this pest were then established providing significant advances toward the understanding of genetic features and the dynamic dispersal of this pest. This study supports the hypothesis of a long-distance dispersal of B. tabaci followed by infrequent long-term isolations. The Inference of population sources and colonization routes is critical for the design and implementation of accurate management strategies against this pest.

  8. Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics.

    Science.gov (United States)

    Jones, Mathew J K; Jallepalli, Prasad V

    2016-01-01

    During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky "gatekeeper" residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells.

  9. Quantitative genetic analysis of anxiety trait in bipolar disorder.

    Science.gov (United States)

    Contreras, J; Hare, E; Chavarría, G; Raventós, H

    2018-01-01

    Bipolar disorder type I (BPI) affects approximately 1% of the world population. Although genetic influences on bipolar disorder are well established, identification of genes that predispose to the illness has been difficult. Most genetic studies are based on categorical diagnosis. One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders. We studied 619 individuals, 568 participants from 61 extended families and 51 unrelated healthy controls. The sample was 55% female and had a mean age of 43.25 (SD 13.90; range 18-78). Heritability and genetic correlation of the trait scale from the Anxiety State and Trait Inventory (STAI) was computed by using the general linear model (SOLAR package software). we observed that anxiety trait meets the following criteria for an endophenotype of bipolar disorder type I (BPI): 1) association with BPI (individuals with BPI showed the highest trait score (F = 15.20 [5,24], p = 0.009), 2) state-independence confirmed after conducting a test-retest in 321 subjects, 3) co-segregation within families 4) heritability of 0.70 (SE: 0.060), p = 2.33 × 10 -14 and 5) genetic correlation with BPI was 0.20, (SE = 0.17, p = 3.12 × 10 -5 ). Confounding factors such as comorbid disorders and pharmacological treatment could affect the clinical relationship between BPI and anxiety trait. Further research is needed to evaluate if anxiety traits are specially related to BPI in comparison with other traits such as anger, attention or response inhibition deficit, pathological impulsivity or low self-directedness. Anxiety trait is a heritable phenotype that follows a normal distribution when measured not only in subjects with BPI but also in unrelated healthy controls. It could be used as an endophenotype in BPI for the identification of genomic regions with susceptibility genes for this disorder. Published by Elsevier B.V.

  10. Longitudinal Analysis of Genetic Susceptibility and BMI Throughout Adult Life.

    Science.gov (United States)

    Song, Mingyang; Zheng, Yan; Qi, Lu; Hu, Frank B; Chan, Andrew T; Giovannucci, Edward L

    2018-02-01

    Little is known about the genetic influence on BMI trajectory throughout adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI-associated variants among 9,971 women and 6,405 men of European ancestry. Serial measures of BMI were assessed from 18 (women) or 21 (men) years to 85 years of age. We also examined BMI change in early (from 18 or 21 to 45 years of age), middle (from 45 to 65 years of age), and late adulthood (from 65 to 80 years of age). GRS was positively associated with BMI across all ages, with stronger associations in women than in men. The associations increased from early to middle adulthood, peaked at 45 years of age in men and at 60 years of age in women (0.91 and 1.35 kg/m 2 per 10-allele increment, respectively) and subsequently declined in late adulthood. For women, each 10-allele increment in the GRS was associated with an average BMI gain of 0.54 kg/m 2 in early adulthood, whereas no statistically significant association was found for BMI change in middle or late adulthood or for BMI change in any life period in men. Our findings indicate that genetic predisposition exerts a persistent effect on adiposity throughout adult life and increases early adulthood weight gain in women. © 2017 by the American Diabetes Association.

  11. Genetic analysis of canine parvovirus from dogs in Australia.

    Science.gov (United States)

    Meers, J; Kyaw-Tanner, M; Bensink, Z; Zwijnenberg, R

    2007-10-01

    To determine the genetic variants of canine parvovirus-2 (CPV) present in domestic dogs in Australia and to investigate 26 cases of apparent vaccine failure. Thirty-three samples of faeces or intestinal tissues and 16 cell culture virus isolates collected over a period from 1980 to 2005 from five Australian states were analysed. Procedure DNA was extracted from the samples and a 1975 bp fragment of the VP1/2 gene of CPV was amplified by polymerase chain reaction (PCR) and sequenced. Sequences were compared to published strains of CPV-2, CPV-2a, CPV-2b and CPV-2c. Forty-one of 43 PCR-positive samples contained CPV-2a viruses. One sample collected in 2002 from a pup in northern NSW contained a CPV-2b virus. One sample that had been included in the study as a CPV-antigen negative control sample contained a CPV-2 virus. CPV-2a remains the predominant genetic variant of CPV in dogs in Australia and has not been replaced by CPV-2b or CPV-2c as in many other countries. The vaccine failures investigated in the study were likely caused not by genetic variation of field viruses but by maternal antibody interference in the response of pups to vaccination.

  12. Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Hannah Elizabeth Henson

    2014-11-01

    Full Text Available The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFPsj2, that expresses enhanced green fluorescent protein (EGFP in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFPsj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease.

  13. A genetic analysis of Trichuris trichiura and Trichuris suis from Ecuador

    DEFF Research Database (Denmark)

    Meekums, Hayley; Hawash, Mohamed B F; Sparks, Alexandra M

    2015-01-01

    BACKGROUND: Since the nematodes Trichuris trichiura and T. suis are morphologically indistinguishable, genetic analysis is required to assess epidemiological cross-over between people and pigs. This study aimed to clarify the transmission biology of trichuriasis in Ecuador. FINDINGS: Adult...... Trichuris worms were collected during a parasitological survey of 132 people and 46 pigs in Esmeraldas Province, Ecuador. Morphometric analysis of 49 pig worms and 64 human worms revealed significant variation. In discriminant analysis morphometric characteristics correctly classified male worms according...... to genetically analyse Trichuris parasites. Although T. trichiura does not appear to be zoonotic in Ecuador, there is evidence of genetic exchange between T. trichiura and T. suis warranting more detailed genetic sampling....

  14. Combining Ability Analysis and Genetic-Effects Studies for Some Important Quality Characters in Brassica napus L.

    Directory of Open Access Journals (Sweden)

    Aamar Shehzad

    2015-10-01

    Full Text Available Combining ability analysis has an important position in rapeseed breeding. To evaluate genetic and combining ability effects, three Brassica napus L. testers “Punjab Sarson, Legend and Durre-NIFA” and five lines “Duncled, K-258, ZN-R-1, ZN-R-8, ZN-M-6” were crossed using line × tester design in Randomized Complete Block Design (RCBD with three replications. Mean sum of squares of the analysis of variances (ANOVA for genotypes was highly significant for all of the traits. Most of the lines and testers exhibited significant results of mean sum of squares for combining ability. Line ‘Duncled’ was proved good general combiner for oil (8.8, protein (3.7, erucic acid (33.0, oleic acid (13.0 and glucosinolate (-19.3 over other lines and tester ‘Durree-NIFA’ for protein (6.6, erucic acid (-23.4, and linolenic acid (-5.3 over other testers. Significant specific combining ability effects were also observed. The best hybrid combinations were Legend × ZN-R-1 for oil (9.6, Punjab Sarson × Duncled for minimum erucic acid (-14.0 and linolenic acid contents (-6.0, and Legend × ZN-M-6 for maximum protein (8.2 and minimum glucosinolate contents (-11.1. The maximum oil contents were observed in ‘Legend × ZN-R-1’ (52.4%. The cross ‘Punjab Sarson × Duncled’ expressed maximum values of protein (26.5% and oleic acid (62.5% while minimum for erucic acid (2.3%, linolenic acid (5.4% and glucosinolate contents (19.3µmol/g. This research discloses the significance of non-additive genetic effects for most of the studied traits except oil contents. These studies will also help to improve nutritional values of rapeseed crop by selecting noble crosses.

  15. QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field.

    Science.gov (United States)

    Delprato, A; Algéo, M-P; Bonheur, B; Bubier, J A; Lu, L; Williams, R W; Chesler, E J; Crusio, W E

    2017-11-01

    The open field is a classic test used to assess exploratory behavior, anxiety and locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20-min test sessions including (1) percent time spent and distance traveled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at approximately 104 Mb that modulates grooming duration in both males and females (likelihood ratio statistic values of approximately 18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found 2 highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  16. Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication

    OpenAIRE

    Pudupakam, R. S.; Kenney, Scott P.; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A.; LeRoith, Tanya; Pierson, F. William; Meng, Xiang-Jin

    2011-01-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication...

  17. Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.

    Science.gov (United States)

    Shchetynsky, Klementy; Diaz-Gallo, Lina-Marcella; Folkersen, Lasse; Hensvold, Aase Haj; Catrina, Anca Irinel; Berg, Louise; Klareskog, Lars; Padyukov, Leonid

    2017-02-02

    Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls. There were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples. Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.

  18. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  19. The Legal Road To Replicating Silicon Valley

    OpenAIRE

    John Armour; Douglas Cumming

    2004-01-01

    Must policymakers seeking to replicate the success of Silicon Valley’s venture capital market first replicate other US institutions, such as deep and liquid stock markets? Or can legal reforms alone make a significant difference? In this paper, we compare the economic and legal determinants of venture capital investment, fundraising and exits. We introduce a cross-sectional and time series empirical analysis across 15 countries and 13 years of data spanning an entire business cycle. We show t...

  20. Hierarchical linear modeling of longitudinal pedigree data for genetic association analysis

    DEFF Research Database (Denmark)

    Tan, Qihua; B Hjelmborg, Jacob V; Thomassen, Mads

    2014-01-01

    -effect models to explicitly model the genetic relationship. These have proved to be an efficient way of dealing with sample clustering in pedigree data. Although current algorithms implemented in popular statistical packages are useful for adjusting relatedness in the mixed modeling of genetic effects...... associated with blood pressure with estimated inflation factors of 0.99, suggesting that our modeling of random effects efficiently handles the genetic relatedness in pedigrees. Application to simulated data captures important variants specified in the simulation. Our results show that the method is useful......Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees, which could affect statistical assessment of the genetic effects. Approaches have been proposed to integrate kinship correlation into the mixed...

  1. Genetic Counseling, Professional Values, and Habitus: An Analysis of Disability Narratives in Textbooks.

    Science.gov (United States)

    Reed, Amy R

    2016-10-19

    This article analyzes narrative illustrations in genetic counseling textbooks as a way of understanding professional habitus--the dispositions that motivate professional behavior. In particular, this analysis shows that there are significant differences in how the textbooks' expository and narrative portions represent Down syndrome, genetic counseling practice, and patient behaviors. While the narrative portions of the text position the genetic counseling profession as working in service to the values of genetic medicine, the expository portions represent genetic counselors as neutral parties. Ultimately, this article argues that this ambiguity is harmful to the production of a professional habitus that is consistent with espoused professional values concerning respect for persons with disabilities and the promotion of psychosocial counseling.

  2. Two-level mixed modeling of longitudinal pedigree data for genetic association analysis

    DEFF Research Database (Denmark)

    Tan, Q.

    2013-01-01

    of follow-up. Approaches have been proposed to integrate kinship correlation into the mixed effect models to explicitly model the genetic relationship which have been proven as an efficient way for dealing with sample clustering in pedigree data. Although useful for adjusting relatedness in the mixed...... assess the genetic associations with the mean level and the rate of change in a phenotype both with kinship correlation integrated in the mixed effect models. We apply our method to longitudinal pedigree data to estimate the genetic effects on systolic blood pressure measured over time in large pedigrees......Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees which could affect statistical assessment of the genetic effects on both the mean level of the phenotype and its rate of change over the time...

  3. Analysis of genetic variation and potential applications in genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Cardoso, Joao; Andersen, Mikael Rørdam; Herrgard, Markus

    2015-01-01

    scale and resolution by re-sequencing thousands of strains systematically. In this article, we review challenges in the integration and analysis of large-scale re-sequencing data, present an extensive overview of bioinformatics methods for predicting the effects of genetic variants on protein function......Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology......, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic...

  4. Logic analysis and verification of n-input genetic logic circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2017-01-01

    . In this paper, we present an approach to analyze and verify the Boolean logic of a genetic circuit from the data obtained through stochastic analog circuit simulations. The usefulness of this analysis is demonstrated through different case studies illustrating how our approach can be used to verify the expected......Nature is using genetic logic circuits to regulate the fundamental processes of life. These genetic logic circuits are triggered by a combination of external signals, such as chemicals, proteins, light and temperature, to emit signals to control other gene expressions or metabolic pathways...... accordingly. As compared to electronic circuits, genetic circuits exhibit stochastic behavior and do not always behave as intended. Therefore, there is a growing interest in being able to analyze and verify the logical behavior of a genetic circuit model, prior to its physical implementation in a laboratory...

  5. Taming Human Genetic Variability: Transcriptomic Meta-Analysis Guides the Experimental Design and Interpretation of iPSC-Based Disease Modeling

    Directory of Open Access Journals (Sweden)

    Pierre-Luc Germain

    2017-06-01

    Full Text Available Both the promises and pitfalls of the cell reprogramming research platform rest on human genetic variation, making the measurement of its impact one of the most urgent issues in the field. Harnessing large transcriptomics datasets of induced pluripotent stem cells (iPSC, we investigate the implications of this variability for iPSC-based disease modeling. In particular, we show that the widespread use of more than one clone per individual in combination with current analytical practices is detrimental to the robustness of the findings. We then proceed to identify methods to address this challenge and leverage multiple clones per individual. Finally, we evaluate the specificity and sensitivity of different sample sizes and experimental designs, presenting computational tools for power analysis. These findings and tools reframe the nature of replicates used in disease modeling and provide important resources for the design, analysis, and interpretation of iPSC-based studies.

  6. Factors influencing microinjection molding replication quality

    Science.gov (United States)

    Vera, Julie; Brulez, Anne-Catherine; Contraires, Elise; Larochette, Mathieu; Trannoy-Orban, Nathalie; Pignon, Maxime; Mauclair, Cyril; Valette, Stéphane; Benayoun, Stéphane

    2018-01-01

    In recent years, there has been increased interest in producing and providing high-precision plastic parts that can be manufactured by microinjection molding: gears, pumps, optical grating elements, and so on. For all of these applications, the replication quality is essential. This study has two goals: (1) fabrication of high-precision parts using the conventional injection molding machine; (2) identification of robust parameters that ensure production quality. Thus, different technological solutions have been used: cavity vacuuming and the use of a mold coated with DLC or CrN deposits. AFM and SEM analyses were carried out to characterize the replication profile. The replication quality was studied in terms of the process parameters, coated and uncoated molds and crystallinity of the polymer. Specific studies were processed to quantify the replicability of injection molded parts (ABS, PC and PP). Analysis of the Taguchi experimental designs permits prioritization of the impact of each parameter on the replication quality. A discussion taking into account these new parameters and the thermal and spreading properties on the coatings is proposed. It appeared that, in general, increasing the mold temperature improves the molten polymer fill in submicron features except for the steel insert (for which the presence of a vacuum is the most important factor). Moreover, the DLC coating was the best coating to increase the quality of the replication. This result could be explained by the lower thermal diffusivity of this coating. We noted that the viscosity of the polymers is not a primordial factor of the replication quality.

  7. SimHap GUI: an intuitive graphical user interface for genetic association analysis.

    Science.gov (United States)

    Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

    2008-12-25

    Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.

  8. The evolutionary ecology of molecular replicators.

    Science.gov (United States)

    Nee, Sean

    2016-08-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

  9. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Science.gov (United States)

    Griffiths, Samantha J; Koegl, Manfred; Boutell, Chris; Zenner, Helen L; Crump, Colin M; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C; Barry, Gerald; Martin, Kim; Craigon, Marie H; Chen, Rui; Kaza, Lakshmi N; Fossum, Even; Fazakerley, John K; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

    2013-01-01

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to

  10. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Directory of Open Access Journals (Sweden)

    Samantha J Griffiths

    Full Text Available Herpes simplex virus type 1 (HSV-1 is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi screen with a druggable genome small interfering RNA (siRNA library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome

  11. The multi-niche crowding genetic algorithm: Analysis and applications

    Energy Technology Data Exchange (ETDEWEB)

    Cedeno, Walter [Univ. of California, Davis, CA (United States)

    1995-09-01

    The ability of organisms to evolve and adapt to the environment has provided mother nature with a rich and diverse set of species. Only organisms well adapted to their environment can survive from one generation to the next, transferring on the traits, that made them successful, to their offspring. Competition for resources and the ever changing environment drives some species to extinction and at the same time others evolve to maintain the delicate balance in nature. In this disertation we present the multi-niche crowding genetic algorithm, a computational metaphor to the survival of species in ecological niches in the face of competition. The multi-niche crowding genetic algorithm maintains stable subpopulations of solutions in multiple niches in multimodal landscapes. The algorithm introduces the concept of crowding selection to promote mating among members with qirnilar traits while allowing many members of the population to participate in mating. The algorithm uses worst among most similar replacement policy to promote competition among members with similar traits while allowing competition among members of different niches as well. We present empirical and theoretical results for the success of the multiniche crowding genetic algorithm for multimodal function optimization. The properties of the algorithm using different parameters are examined. We test the performance of the algorithm on problems of DNA Mapping, Aquifer Management, and the File Design Problem. Applications that combine the use of heuristics and special operators to solve problems in the areas of combinatorial optimization, grouping, and multi-objective optimization. We conclude by presenting the advantages and disadvantages of the algorithm and describing avenues for future investigation to answer other questions raised by this study.

  12. Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. IV. Influence of DNA replication and excision repair on REV2 dependent UV-mutagenesis and repair

    Energy Technology Data Exchange (ETDEWEB)

    Siede, W.; Eckardt, F.

    1986-01-01

    A double mutant being thermoconditionally defective in mutation induction as well as in repair of pre-lethal UV-induced DNA damage (rev2ts) and deficient in excision repair (rad3-2) was studied in temperature-shift experiments. The influence of inhibitors of DNA replication (hydroxyurea, aphidicolin) was determined. Additionally, an analysis of the dose-response pattern of mutation induction (mutation kinetics) at several ochre alleles was carried out. It was concluded that the UV-inducible REV2 dependent mutagenic repair process is not induced in excision-deficient cells. In excision-deficient cells, REV2 dependent mutation fixation is slow and mostly post-replicative though not dependent on DNA replication. The REV2 mediated mutagenic process could be separated from the repair function.

  13. SNP and haplotype mapping for genetic analysis in the rat

    Czech Academy of Sciences Publication Activity Database

    Saar, K.; Beck, A.; Bihoreau, M. T.; Birney, E.; Brocklebank, D.; Chen, Y.; Cuppen, E.; Demonchy, S.; Dopazo, J.; Flicek, P.; Foglio, M.; Fujiyama, A.; Gut, I. G.; Gauguier, D.; Guigo, R.; Guryev, V.; Heinig, M.; Hummel, O.; Jahn, N.; Klages, S.; Křen, Vladimír; Kube, M.; Kuhl, H.; Kuramoto, T.; Pravenec, Michal

    2008-01-01

    Roč. 40, č. 5 (2008), s. 560-566 ISSN 1061-4036 R&D Projects: GA MŠk(CZ) 1P05ME791; GA MŠk(CZ) 1M0520; GA MŠk(CZ) ME08006 Grant - others:HHMI(US) 55005624; -(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Source of funding: N - neverejné zdroje ; R - rámcový projekt EK Keywords : SNP * rat * complete map Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 30.259, year: 2008

  14. Historical analysis of Newfoundland dog fur colour genetics

    OpenAIRE

    Bondeson, J.

    2015-01-01

    This article makes use of digitized historic newspapers to analyze Newfoundland dog fur colour genetics, and fur colour variations over time. The results indicate that contrary to the accepted view, the ‘Solid’ gene was introduced into the British population of Newfoundland dogs in the 1840s. Prior to that time, the dogs were white and black (Landseer) or white and brown, and thus spotted/spotted homozygotes. Due to ‘Solid’ being dominant over ‘spotted’, and selective breeding, today the majo...

  15. Genetic Analysis of Gravity Signal Transduction in Arabidopsis thaliana Seedlings

    Science.gov (United States)

    Boonsirichai, K.; Harrison, B.; Stanga, J.; Young, L.-S.; Neal, C.; Sabat, G.; Murthy, N.; Harms, A.; Sedbrook, J.; Masson, P.

    The primary roots of Arabidopsis thaliana seedlings respond to gravity stimulation by developing a tip curvature that results from differential cellular elongation on opposite flanks of the elongation zone. This curvature appears modulated by a lateral gradient of auxin that originates in the gravity-perceiving cells (statocytes) of the root cap through an apparent lateral repositioning of a component the auxin efflux carrier complex within these cells (Friml et al, 2002, Nature 415: 806-809). Unfortunately, little is known about the molecular mechanisms that govern early phases of gravity perception and signal transduction within the root-cap statocytes. We have used a molecular genetic approach to uncover some of these mechanisms. Mutations in the Arabidopsis ARG1 and ARL2 genes, which encode J-domain proteins, resulted in specific alterations in root and hypocotyl gravitropism, without pleiotropic phenotypes. Interestingly, ARG1 and ARL2 appear to function in the same genetic pathway. A combination of molecular genetic, biochemical and cell-biological approaches were used to demonstrate that ARG1 functions in early phases of gravity signal transduction within the root and hypocotyl statocytes, and is needed for efficient lateral auxin transport within the cap. The ARG1 protein is associated with components of the secretory and/or endosomal pathways, suggesting its role in the recycling of components of the auxin efflux carrier complex between plasma membrane and endosome (Boonsirichai et al, 2003, Plant Cell 15:2612-2625). Genetic modifiers of arg1-2 were isolated and shown to enhance the gravitropic defect of arg1-2, while resulting in little or no gravitropic defects in a wild type ARG1 background. A slight tendency for arg1-2;mar1-1 and arg1-2;mar2-1 double-mutant organs to display an opposite gravitropic response compared to wild type suggests that all three genes contribute to the interpretation of the gravity-vector information by seedling organs. The

  16. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  17. Population genetic analysis and trichothecene profiling of Fusarium graminearum from wheat in Uruguay.

    Science.gov (United States)

    Pan, D; Mionetto, A; Calero, N; Reynoso, M M; Torres, A; Bettucci, L

    2016-03-11

    Fusarium graminearum sensu stricto (F. graminearum s.s.) is the major causal agent of Fusarium head blight of wheat worldwide, and contaminates grains with trichothecene mycotoxins that cause serious threats to food safety and animal health. An important aspect of managing this pathogen and reducing mycotoxin contamination of wheat is knowledge regarding its population genetics. Therefore, isolates of F. graminearum s.s. from the major wheat-growing region of Uruguay were analyzed by amplified fragment length polymorphism assays, PCR genotyping, and chemical analysis of trichothecene production. Of the 102 isolates identified as having the 15-ADON genotype via PCR genotyping, all were DON producers, but only 41 strains were also 15-ADON producers, as determined by chemical analysis. The populations were genotypically diverse but genetically similar, with significant genetic exchange occurring between them. Analysis of molecular variance indicated that most of the genetic variability resulted from differences between isolates within populations. Multilocus linkage disequilibrium analysis suggested that the isolates had a panmictic population genetic structure and that there is significant recombination occurs in F. graminearum s.s. In conclusion, tour findings provide the first detailed description of the genetic structure and trichothecene production of populations of F. graminearum s.s. from Uruguay, and expands our understanding of the agroecology of F. graminearum and of the correlation between genotypes and trichothecene chemotypes.

  18. Genetic diversity analysis of Cuban traditional rice (Oryza sativa L. varieties based on microsatellite markers

    Directory of Open Access Journals (Sweden)

    Alba Alvarez

    2007-01-01

    Full Text Available Microsatellite polymorphism was studied in a sample of 39 traditional rice (Oryza sativa L. varieties and 11 improved varieties widely planted in Cuba. The study was aimed at assessing the extent of genetic variation in traditional and improved varieties and to establish their genetic relationship for breeding purposes. Heterozygosity was analyzed at each microsatellite loci and for each genotype using 10 microsatellite primer pairs. Between varieties genetic relationship was estimated. The number of alleles per microsatellite loci was 4 to 8, averaging 6.6 alleles per locus. Higher heterozygosity (H was found in traditional varieties (H TV = 0.72 than in improved varieties (H IV = 0.42, and 68% of the total microsatellite alleles were found exclusively in the traditional varieties. Genetic diversity, represented by cluster analysis, indicated three different genetic groups based on their origin. Genetic relationship estimates based on the proportion of microsatellite loci with shared alleles indicated that the majority of traditional varieties were poorly related to the improved varieties. We also discuss the more efficient use of the available genetic diversity in future programs involving genetic crosses.

  19. MetaGenyo: a web tool for meta-analysis of genetic association studies.

    Science.gov (United States)

    Martorell-Marugan, Jordi; Toro-Dominguez, Daniel; Alarcon-Riquelme, Marta E; Carmona-Saez, Pedro

    2017-12-16

    Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .

  20. Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis)

    Science.gov (United States)

    FUNK, W. CHRIS; LOVICH, ROBERT E.; HOHENLOHE, PAUL A.; HOFMAN, COURTNEY A.; MORRISON, SCOTT A.; SILLETT, T. SCOTT; GHALAMBOR, CAMERON K.; MALDONADO, JESUS E.; RICK, TORBEN C.; DAY, MITCH D.; POLATO, NICHOLAS R.; FITZPATRICK, SARAH W.; COONAN, TIMOTHY J.; CROOKS, KEVIN R.; DILLON, ADAM; GARCELON, DAVID K.; KING, JULIE L.; BOSER, CHRISTINA L.; GOULD, NICHOLAS; ANDELT, WILLIAM F.

    2016-01-01

    The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of 6 subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland gray foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness, and reduced adaptive potential. PMID:26992010

  1. Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis).

    Science.gov (United States)

    Funk, W Chris; Lovich, Robert E; Hohenlohe, Paul A; Hofman, Courtney A; Morrison, Scott A; Sillett, T Scott; Ghalambor, Cameron K; Maldonado, Jesus E; Rick, Torben C; Day, Mitch D; Polato, Nicholas R; Fitzpatrick, Sarah W; Coonan, Timothy J; Crooks, Kevin R; Dillon, Adam; Garcelon, David K; King, Julie L; Boser, Christina L; Gould, Nicholas; Andelt, William F

    2016-05-01

    The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1-89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6-6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential. © 2016 John Wiley & Sons Ltd.

  2. Sterol Binding by the Tombusviral Replication Proteins Is Essential for Replication in Yeast and Plants.

    Science.gov (United States)

    Xu, Kai; Nagy, Peter D

    2017-04-01

    heterogeneous and highly dynamic nanoscale structures usurped by various viruses. Here, we demonstrate that TBSV p33 and p92 replication proteins can bind to sterol in vitro Mutagenesis analysis of p33 within the CRAC and CARC sequences involved in sterol binding shows the important connection between the abilities of p33 to bind to sterol and to support TBSV replication in yeast and plant cells. Together, the results further strengthen the model that cellular sterols are essential as proviral lipids during viral replication. Copyright © 2017 American Society for Microbiology.

  3. Genetic analysis of calf and heifer losses in Danish Holstein

    DEFF Research Database (Denmark)

    Fuerst-Walti, B; Sørensen, Morten Kargo

    2010-01-01

    Mortality in dairy cattle is not only relevant with regard to economic losses but also to animal health and welfare. Thus, the aim of this investigation was to explore the genetic background of postnatal mortality in calves and replacement heifers in different age groups until first calving...... periods, whereas their records were kept for preceding periods. After further data editing, more than 840,000 calves and heifers born in the years 1998 to 2007 were investigated. Mortality rates were 3.23, 2.66, 0.97, 1.92, and 9.36% for the defined periods P1 to P5, respectively. For the estimation...... of genetic parameters, linear and threshold sire models were applied. Effects accounted for were the random effects herd × year × season and sire as well as the fixed effects year × month, number of dam's parity (parities >5 were set to 5), calf size, and calving ease. In total, the pedigree consisted of 4...

  4. Histone Modification Associated with Initiation of DNA Replication | Center for Cancer Research

    Science.gov (United States)

    Before cells are able to divide, they must first duplicate their chromosomes accurately. DNA replication and packaging of DNA into chromosomes by histone proteins need to be coordinated by the cell to ensure proper transmission of genetic and epigenetic information to the next generation. Mammalian DNA replication begins at specific chromosomal sites, called replication

  5. Elg1 forms an alternative RFC complex important for DNA replication and genome integrity

    NARCIS (Netherlands)

    Bellaoui, Mohammed; Chang, Michael; Ou, Jiongwen; Xu, Hong; Boone, Charles; Brown, Grant W

    2003-01-01

    Genome-wide synthetic genetic interaction screens with mutants in the mus81 and mms4 replication fork-processing genes identified a novel replication factor C (RFC) homolog, Elg1, which forms an alternative RFC complex with Rfc2-5. This complex is distinct from the DNA replication RFC, the DNA

  6. Genetic diversity and structure analysis based on hordein protein polymorphism in barley landrace populations from jordan

    International Nuclear Information System (INIS)

    Baloch, A.W.; Ali, M.; Baloch, A.M.; Mangan, B.U.N.; Song, W

    2014-01-01

    Jordan is unanimously considered to be one of the centers of genetic diversity for barley, where wild and landraces of barley has been grown under different climatic conditions. The genetic diversity and genetic structure based on hordein polymorphism was assessed in 90 different accessions collected from four different sites of Jordan. A-PAGE was used to reveal hordein polymorphism among the genotypes. A total of 29 distinct bands were identified, out of them 9 bands were distinguished for D, 11 for C, and 9 for the B hordein regions. The observed genetic similarity was an exceptionally high between the populations than expected, which is probably due to high gene flow estimated between them. The genetic diversity parameters were not differ largely among the populations, indicating that local selection of a particular site did not play a key role in shaping genetic diversity. Analysis of molecular variance (AMOVA) revealed significant population structure when accessions were structured according to population site. There was 94% of hordein variation resided within the populations and only 8% present among the populations. Both Bayesian and Principale Coordinate Analysis (PCoA) concordantly demonstrated admixture genotypes of the landraces barley populations. Consequently, none of the population found to be clustered separately according to its population site. It is concluded that this approach can be useful to explore the germplasm for genetic diversity but perhaps is not suitable for determining phylogenic relations in barley. (author)

  7. Genetic analysis of 430 Chinese Cynodon dactylon accessions using sequence-related amplified polymorphism markers.

    Science.gov (United States)

    Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

    2014-10-21

    Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260-1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53-0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars.

  8. Genetic Analysis for Two Italian Siblings with Usher Syndrome and Schizophrenia

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2012-01-01

    Full Text Available Usher syndrome is a group of autosomal recessive genetic disorders characterized by deafness, retinitis pigmentosa, and sometimes vestibular areflexia. The relationship between Usher syndrome and mental disorders, most commonly a “schizophrenia-like” psychosis, is sometimes described in the literature. The etiology of psychiatric expression of Usher syndrome is still unclear. We reported a case of two natural siblings with congenital hypoacusis, retinitis pigmentosa, and psychiatric symptoms. Clinical features and genetic analysis were also reported. We analyzed possible causes to explain the high prevalence of psychiatric manifestations in Usher syndrome: genetic factors, brain damage, and “stress-related” hypothesis.

  9. Genetic analysis for two italian siblings with usher syndrome and schizophrenia.

    Science.gov (United States)

    Domanico, Daniela; Fragiotta, Serena; Trabucco, Paolo; Nebbioso, Marcella; Vingolo, Enzo Maria

    2012-01-01

    Usher syndrome is a group of autosomal recessive genetic disorders characterized by deafness, retinitis pigmentosa, and sometimes vestibular areflexia. The relationship between Usher syndrome and mental disorders, most commonly a "schizophrenia-like" psychosis, is sometimes described in the literature. The etiology of psychiatric expression of Usher syndrome is still unclear. We reported a case of two natural siblings with congenital hypoacusis, retinitis pigmentosa, and psychiatric symptoms. Clinical features and genetic analysis were also reported. We analyzed possible causes to explain the high prevalence of psychiatric manifestations in Usher syndrome: genetic factors, brain damage, and "stress-related" hypothesis.

  10. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 80; Issue 1. Testing quantum dynamics in genetic information processing ... Keywords. assembly; computation; database search; DNA replication; genetic information; nucleotide base; polymerase enzyme; quantum coherence; quantum mechanics; quantum superposition.

  11. Genetic analysis of PAX3 for diagnosis of Waardenburg syndrome type I.

    Science.gov (United States)

    Matsunaga, Tatsuo; Mutai, Hideki; Namba, Kazunori; Morita, Noriko; Masuda, Sawako

    2013-04-01

    PAX3 genetic analysis increased the diagnostic accuracy for Waardenburg syndrome type I (WS1). Analysis of the three-dimensional (3D) structure of PAX3 helped verify the pathogenicity of a missense mutation, and multiple ligation-dependent probe amplification (MLPA) analysis of PAX3 increased the sensitivity of genetic diagnosis in patients with WS1. Clinical diagnosis of WS1 is often difficult in individual patients with isolated, mild, or non-specific symptoms. The objective of the present study was to facilitate the accurate diagnosis of WS1 through genetic analysis of PAX3 and to expand the spectrum of known PAX3 mutations. In two Japanese families with WS1, we conducted a clinical evaluation of symptoms and genetic analysis, which involved direct sequencing, MLPA analysis, quantitative PCR of PAX3, and analysis of the predicted 3D structure of PAX3. The normal-hearing control group comprised 92 subjects who had normal hearing according to pure tone audiometry. In one family, direct sequencing of PAX3 identified a heterozygous mutation, p.I59F. Analysis of PAX3 3D structures indicated that this mutation distorted the DNA-binding site of PAX3. In the other family, MLPA analysis and subsequent quantitative PCR detected a large, heterozygous deletion spanning 1759-2554 kb that eliminated 12-18 genes including a whole PAX3 gene.

  12. pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes

    Directory of Open Access Journals (Sweden)

    Arévalo-Rodríguez Miguel

    2011-02-01

    Full Text Available Abstract Background Since publication in 1977 of plasmid pBR322, many breakthroughs in Biology have depended on increasingly sophisticated vector platforms for analysis and engineering of given bacterial strains. Although restriction sites impose a certain format in the procedures for assembling cloned genes, every attempt thus far to standardize vector architecture and nomenclature has ended up in failure. While this state of affairs may still be tolerable for traditional one-at-a-time studies of single genes, the onset of systems and synthetic biology calls for a simplification -along with an optimization- of the currently unwieldy pool of genetic tools. Results The functional DNA sequences present in the natural bacterial transposon Tn5 have been methodically edited and refactored for the production of a multi-purpose genetic tool named pBAM1, which allows a range of manipulations in the genome of Gram-negative bacteria. This all-synthetic construct enhances the power of mini-transposon vectors for either de-construction or re-construction of phenotypes á la carte by incorporating features inspired in systems engineering: modularity, re-usability, minimization, and compatibility with other genetic tools. pBAM1 bears an streamlined, restriction site-freed and narrow-host range replication frame bearing the sequences of R6K oriV, oriT and an ampicillin resistance marker. These go along with a business module that contains a host-independent and hyperactive transposition platform for in vivo or in vitro insertion of desired DNA into the genome of the target bacterium. All functional sequences were standardized for a straightforward replacement by equivalent counterparts, if required. pBAM1 can be delivered into recipient cells by either mating or electroporation, producing transposon insertion frequencies of 1.8 × 10-3 and 1.02 × 10-7, respectively in the soil bacterium Pseudomonas putida. Analyses of the resulting clones revealed a 100% of

  13. Emerging Global Initiatives in Neurogenetics: The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium.

    Science.gov (United States)

    Bearden, Carrie E; Thompson, Paul M

    2017-04-19

    The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain. This "crowdsourcing" approach to team neuroscience has unprecedented power for advancing our understanding of both typical and atypical human brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Variable-number-of-tandem-repeats analysis of genetic diversity in Pasteuria ramosa.

    Science.gov (United States)

    Mouton, L; Ebert, D

    2008-05-01

    Variable-number-of-tandem-repeats (VNTR) markers are increasingly being used in population genetic studies of bacteria. They were recently developed for Pasteuria ramosa, an endobacterium that infects Daphnia species. In the present study, we genotyped P. ramosa in 18 infected hosts from the United Kingdom, Belgium, and two lakes in the United States using seven VNTR markers. Two Daphnia species were collected: D. magna and D. dentifera. Six loci showed length polymorphism, with as many as five alleles identified for a single locus. Similarity coefficient calculations showed that the extent of genetic variation between pairs of isolates within populations differed according to the population, but it was always less than the genetic distances among populations. Analysis of the genetic distances performed using principal component analysis revealed strong clustering by location of origin, but not by host Daphnia species. Our study demonstrated that the VNTR markers available for P. ramosa are informative in revealing genetic differences within and among populations and may therefore become an important tool for providing detailed analysis of population genetics and epidemiology.

  15. Historical analysis of Newfoundland dog fur colour genetics

    Directory of Open Access Journals (Sweden)

    J. Bondeson

    2015-06-01

    Full Text Available This article makes use of digitized historic newspapers to analyze Newfoundland dog fur colour genetics, and fur colour variations over time. The results indicate that contrary to the accepted view, the ‘Solid’ gene was introduced into the British population of Newfoundland dogs in the 1840s. Prior to that time, the dogs were white and black (Landseer or white and brown, and thus spotted/spotted homozygotes. Due to ‘Solid’ being dominant over ‘spotted’, and selective breeding, today the majority of Newfoundland dogs are solid black. Whereas small white marks on the chest and/or paw appears to be a random event, the historical data supports the existence of an ‘Irish spotted’ fur colour pattern, with white head blaze, breast, paws and tail tip, in spotted/spotted homozygotes.

  16. Analysis of Shrinkage on Thick Plate Part using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Najihah S.N.

    2016-01-01

    Full Text Available Injection moulding is the most widely used processes in manufacturing plastic products. Since the quality of injection improves plastic parts are mostly influenced by process conditions, the method to determine the optimum process conditions becomes the key to improving the part quality. This paper presents a systematic methodology to analyse the shrinkage of the thick plate part during the injection moulding process. Genetic Algorithm (GA method was proposed to optimise the process parameters that would result in optimal solutions of optimisation goals. Using the GA, the shrinkage of the thick plate part was improved by 39.1% in parallel direction and 17.21% in the normal direction of melt flow.

  17. Genetic analysis of Ras genes in epidermal development and tumorigenesis

    Science.gov (United States)

    Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

    2013-01-01

    Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

  18. Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

    Science.gov (United States)

    Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

    2016-01-01

    Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific

  19. Sucrose accumulation in watermelon fruits: genetic variation and biochemical analysis.

    Science.gov (United States)

    Yativ, Merav; Harary, Idan; Wolf, Shmuel

    2010-05-15

    Sugar accumulation, the key process determining fruit quality, is controlled by both the translocation of sugars and their metabolism in developing fruits. Sugar composition in watermelon, as in all cucurbit fruits, includes sucrose, fructose and glucose. The proportions of these three sugars are determined primarily by three enzyme families: invertases, sucrose synthases (SuSys) and sucrose phosphate synthases (SPSs). The goal of the present research was to explore the process of sugar metabolism in watermelon fruits. Crosses between the domestic watermelon (Citrullus lanatus) and three wild species provided a wide germplasm to explore genetic variability in sugar composition and metabolism. This survey demonstrated great genetic variability in sugar content and in the proportions of sucrose, glucose and fructose in mature fruits. Genotypes accumulating high and low percentage of sucrose provided an experimental system to study sugar metabolism in developing fruits. Insoluble invertase activity was high and constant throughout fruit development in control lines and in genotypes accumulating low levels of sucrose, while in genotypes accumulating high levels of sucrose, activity declined sharply 4 weeks after pollination. Soluble acid invertase activity was significantly lower in genotypes accumulating high levels of sucrose than in low-sucrose-accumulating genotypes. Conversely, activities of SuSy and SPS were higher in the high-sucrose-accumulating genotypes. The present results establish that, within the genus Citrullus, there are genotypes that accumulate a high percentage of sucrose in the fruit, while others accumulate high percentages of glucose and fructose. The significant negative correlation between insoluble invertase activity and fruit sucrose level suggests that sucrose accumulation is affected by both phloem unloading and sugar metabolism. (c) 2009 Elsevier GmbH. All rights reserved.

  20. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

    Science.gov (United States)

    Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

    2016-08-09

    Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.