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Sample records for genome-wide breeding values

  1. Genome Wide Screening of Candidate Genes for Improving Piglet Birth Weight Using High and Low Estimated Breeding Value Populations

    PubMed Central

    Zhang, Lifan; Zhou, Xiang; Michal, Jennifer J.; Ding, Bo; Li, Rui; Jiang, Zhihua

    2014-01-01

    Birth weight is an economically important trait in pig production because it directly impacts piglet growth and survival rate. In the present study, we performed a genome wide survey of candidate genes and pathways associated with individual birth weight (IBW) using the Illumina PorcineSNP60 BeadChip on 24 high (HEBV) and 24 low estimated breeding value (LEBV) animals. These animals were selected from a reference population of 522 individuals produced by three sires and six dam lines, which were crossbreds with multiple breeds. After quality-control, 43,257 SNPs (single nucleotide polymorphisms), including 42,243 autosomal SNPs and 1,014 SNPs on chromosome X, were used in the data analysis. A total of 27 differentially selected regions (DSRs), including 1 on Sus scrofa chromosome 1 (SSC1), 1 on SSC4, 2 on SSC5, 4 on SSC6, 2 on SSC7, 5 on SSC8, 3 on SSC9, 1 on SSC14, 3 on SSC18, and 5 on SSCX, were identified to show the genome wide separations between the HEBV and LEBV groups for IBW in piglets. A DSR with the most number of significant SNPs (including 7 top 0.1% and 31 top 5% SNPs) was located on SSC6, while another DSR with the largest genetic differences in FST was found on SSC18. These regions harbor known functionally important genes involved in growth and development, such as TNFRSF9 (tumor necrosis factor receptor superfamily member 9), CA6 (carbonic anhydrase VI) and MDFIC (MyoD family inhibitor domain containing). A DSR rich in imprinting genes appeared on SSC9, which included PEG10 (paternally expressed 10), SGCE (sarcoglycan, epsilon), PPP1R9A (protein phosphatase 1, regulatory subunit 9A) and ASB4 (ankyrin repeat and SOCS box containing 4). More importantly, our present study provided evidence to support six quantitative trait loci (QTL) regions for pig birth weight, six QTL regions for average birth weight (ABW) and three QTL regions for litter birth weight (LBW) reported previously by other groups. Furthermore, gene ontology analysis with 183 genes

  2. Genome-wide association and prediction of direct genomic breeding values for composition of fatty acids in Angus beef cattlea

    PubMed Central

    2013-01-01

    Background As consumers continue to request food products that have health advantages, it will be important for the livestock industry to supply a product that meet these demands. One such nutrient is fatty acids, which have been implicated as playing a role in cardiovascular disease. Therefore, the objective of this study was to determine the extent to which molecular markers could account for variation in fatty acid composition of skeletal muscle and identify genomic regions that harbor genetic variation. Results Subsets of markers on the Illumina 54K bovine SNPchip were able to account for up to 57% of the variance observed in fatty acid composition. In addition, these markers could be used to calculate a direct genomic breeding values (DGV) for a given fatty acids with an accuracy (measured as simple correlations between DGV and phenotype) ranging from -0.06 to 0.57. Furthermore, 57 1-Mb regions were identified that were associated with at least one fatty acid with a posterior probability of inclusion greater than 0.90. 1-Mb regions on BTA19, BTA26 and BTA29, which harbored fatty acid synthase, Sterol-CoA desaturase and thyroid hormone responsive candidate genes, respectively, explained a high percentage of genetic variance in more than one fatty acid. It was also observed that the correlation between DGV for different fatty acids at a given 1-Mb window ranged from almost 1 to -1. Conclusions Further investigations are needed to identify the causal variants harbored within the identified 1-Mb windows. For the first time, Angus breeders have a tool whereby they could select for altered fatty acid composition. Furthermore, these reported results could improve our understanding of the biology of fatty acid metabolism and deposition. PMID:24156620

  3. Genome-wide Association Study (GWAS) and Its Application for Improving the Genomic Estimated Breeding Values (GEBV) of the Berkshire Pork Quality Traits

    PubMed Central

    Lee, Young-Sup; Jeong, Hyeonsoo; Taye, Mengistie; Kim, Hyeon Jeong; Ka, Sojeong; Ryu, Youn-Chul; Cho, Seoae

    2015-01-01

    The missing heritability has been a major problem in the analysis of best linear unbiased prediction (BLUP). We introduced the traditional genome-wide association study (GWAS) into the BLUP to improve the heritability estimation. We analyzed eight pork quality traits of the Berkshire breeds using GWAS and BLUP. GWAS detects the putative quantitative trait loci regions given traits. The single nucleotide polymorphisms (SNPs) were obtained using GWAS results with p value <0.01. BLUP analyzed with significant SNPs was much more accurate than that with total genotyped SNPs in terms of narrow-sense heritability. It implies that genomic estimated breeding values (GEBVs) of pork quality traits can be calculated by BLUP via GWAS. The GWAS model was the linear regression using PLINK and BLUP model was the G-BLUP and SNP-GBLUP. The SNP-GBLUP uses SNP-SNP relationship matrix. The BLUP analysis using preprocessing of GWAS can be one of the possible alternatives of solving the missing heritability problem and it can provide alternative BLUP method which can find more accurate GEBVs. PMID:26580278

  4. Genome-wide genetic changes during modern breeding of maize.

    PubMed

    Jiao, Yinping; Zhao, Hainan; Ren, Longhui; Song, Weibin; Zeng, Biao; Guo, Jinjie; Wang, Baobao; Liu, Zhipeng; Chen, Jing; Li, Wei; Zhang, Mei; Xie, Shaojun; Lai, Jinsheng

    2012-07-01

    The success of modern maize breeding has been demonstrated by remarkable increases in productivity over the last four decades. However, the underlying genetic changes correlated with these gains remain largely unknown. We report here the sequencing of 278 temperate maize inbred lines from different stages of breeding history, including deep resequencing of 4 lines with known pedigree information. The results show that modern breeding has introduced highly dynamic genetic changes into the maize genome. Artificial selection has affected thousands of targets, including genes and non-genic regions, leading to a reduction in nucleotide diversity and an increase in the proportion of rare alleles. Genetic changes during breeding happen rapidly, with extensive variation (SNPs, indels and copy-number variants (CNVs)) occurring, even within identity-by-descent regions. Our genome-wide assessment of genetic changes during modern maize breeding provides new strategies as well as practical targets for future crop breeding and biotechnology. PMID:22660547

  5. Genome-Wide Specific Selection in Three Domestic Sheep Breeds

    PubMed Central

    Cao, Jiaxve; Wu, Mingming; Ma, Xiaomeng; Liu, Zhen; Liu, Ruizao; Zhao, Fuping; Wei, Caihong; Du, Lixin

    2015-01-01

    Background Commercial sheep raised for mutton grow faster than traditional Chinese sheep breeds. Here, we aimed to evaluate genetic selection among three different types of sheep breed: two well-known commercial mutton breeds and one indigenous Chinese breed. Results We first combined locus-specific branch lengths and di statistical methods to detect candidate regions targeted by selection in the three different populations. The results showed that the genetic distances reached at least medium divergence for each pairwise combination. We found these two methods were highly correlated, and identified many growth-related candidate genes undergoing artificial selection. For production traits, APOBR and FTO are associated with body mass index. For meat traits, ALDOA, STK32B and FAM190A are related to marbling. For reproduction traits, CCNB2 and SLC8A3 affect oocyte development. We also found two well-known genes, GHR (which affects meat production and quality) and EDAR (associated with hair thickness) were associated with German mutton merino sheep. Furthermore, four genes (POL, RPL7, MSL1 and SHISA9) were associated with pre-weaning gain in our previous genome-wide association study. Conclusions Our results indicated that combine locus-specific branch lengths and di statistical approaches can reduce the searching ranges for specific selection. And we got many credible candidate genes which not only confirm the results of previous reports, but also provide a suite of novel candidate genes in defined breeds to guide hybridization breeding. PMID:26083354

  6. A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identi...

  7. A genome-wide scan for signatures of differential artificial selection in ten cattle breeds

    PubMed Central

    2013-01-01

    Background Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH). Results We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content. Conclusions These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass

  8. Genome-wide association analysis for quantitative trait loci influencing Warner–Bratzler shear force in five taurine cattle breeds

    PubMed Central

    McClure, M C; Ramey, H R; Rolf, M M; McKay, S D; Decker, J E; Chapple, R H; Kim, J W; Taxis, T M; Weaber, R L; Schnabel, R D; Taylor, J F

    2012-01-01

    Summary We performed a genome-wide association study for Warner–Bratzler shear force (WBSF), a measure of meat tenderness, by genotyping 3360 animals from five breeds with 54 790 BovineSNP50 and 96 putative single-nucleotide polymorphisms (SNPs) within μ-calpain [HUGO nomenclature calpain 1, (mu/I) large subunit; CAPN1] and calpastatin (CAST). Within- and across-breed analyses estimated SNP allele substitution effects (ASEs) by genomic best linear unbiased prediction (GBLUP) and variance components by restricted maximum likelihood under an animal model incorporating a genomic relationship matrix. GBLUP estimates of ASEs from the across-breed analysis were moderately correlated (0.31–0.66) with those from the individual within-breed analyses, indicating that prediction equations for molecular estimates of breeding value developed from across-breed analyses should be effective for genomic selection within breeds. We identified 79 genomic regions associated with WBSF in at least three breeds, but only eight were detected in all five breeds, suggesting that the within-breed analyses were underpowered, that different quantitative trait loci (QTL) underlie variation between breeds or that the BovineSNP50 SNP density is insufficient to detect common QTL among breeds. In the across-breed analysis, CAPN1 was followed by CAST as the most strongly associated WBSF QTL genome-wide, and associations with both were detected in all five breeds. We show that none of the four commercialized CAST and CAPN1SNP diagnostics are causal for associations with WBSF, and we putatively fine-map the CAPN1 causal mutation to a 4581-bp region. We estimate that variation in CAST and CAPN1 explains 1.02 and 1.85% of the phenotypic variation in WBSF respectively. PMID:22497286

  9. A genome-wide association study of malting quality across eight U.S. barley breeding programs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study leverages the breeding data of 1,862 breeding lines evaluated in 97 field trials for genome-wide association study of malting quality traits in barley. The breeding lines were six-row and two-row barley advanced breeding lines from eight barley breeding populations established at six pub...

  10. A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

    PubMed Central

    Kijas, James W.; Townley, David; Dalrymple, Brian P.; Heaton, Michael P.; Maddox, Jillian F.; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G.; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V. Hutton; Nicholas, Frank W.; Raadsma, Herman

    2009-01-01

    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability. PMID:19270757

  11. Opportunities for genome-wide selection for pig breeding in developing countries.

    PubMed

    Akanno, E C; Schenkel, F S; Sargolzaei, M; Friendship, R M; Robinson, J A B

    2013-07-26

    Genetic improvement of exotic and indigenous pigs in tropical developing countries is desired. Implementations of traditional selection methods on tropical pig populations are limited by lack of data recording and analysis infrastructure. Genome-wide selection (GS) provides an approach for achieving faster genetic progress without developing a pedigree recording system. The implications of GS on long term gain and inbreeding should be studied before actual implementation especially where low linkage disequilibrium (LD) is anticipated in the target population. A simulation case-study of this option was carried out based on the available 60 K SNP panel for porcine genome. Computer simulation was used to explore the effects of various selection methods, trait heritability and different breeding programs when applying GS. Genomic predictions were based on the ridge regression method. Genome-wide selection performed better than BLUP and phenotypic selection methods by increasing genetic gain and maintaining genetic variation while lowering inbreeding especially for traits with low heritability. Indigenous pig populations with low LD can be improved by using GS if high density marker panels are available. The combination of GS with repeated backcrossing of crossbreds to exotic pigs in developing countries promises to rapidly improve the genetic merit of the commercial population. Application of this novel method on a real population will need to be carried out to validate these results. PMID:23893977

  12. Opportunities for genome-wide selection for pig breeding in developing countries.

    PubMed

    Akanno, E C; Schenkel, F S; Sargolzaei, M; Friendship, R M; Robinson, J A B

    2013-10-01

    Genetic improvement of exotic and indigenous pigs in tropical developing countries is desired. Implementations of traditional selection methods on tropical pig populations are limited by lack of data recording and analysis infrastructure. Genome-wide selection (GS) provides an approach for achieving faster genetic progress without developing a pedigree recording system. The implications of GS on long-term gain and inbreeding should be studied before actual implementation, especially where low linkage disequilibrium (LD) is anticipated in the target population. A simulation case study of this option was performed on the basis of the available 60,000 SNP panel for porcine genome. Computer simulation was used to explore the effects of various selection methods, trait heritability, and different breeding programs when applying GS. Genomic predictions were based on the ridge regression method. Genome-wide selection performed better than BLUP and phenotypic selection methods by increasing genetic gain and maintaining genetic variation while lowering inbreeding, especially for traits with low heritability. Indigenous pig populations with low LD can be improved by using GS if high-density marker panels are available. The combination of GS with repeated backcrossing of crossbreds to exotic pigs in developing countries promises to rapidly improve the genetic merit of the commercial population. Application of this novel method on a real population will need to be performed to validate these results. PMID:24078617

  13. Genome-wide analysis of DNA methylation in obese, lean, and miniature pig breeds

    PubMed Central

    Yang, Yalan; Zhou, Rong; Mu, Yulian; Hou, Xinhua; Tang, Zhonglin; Li, Kui

    2016-01-01

    DNA methylation is a crucial epigenetic modification involved in diverse biological processes. There is significant phenotypic variance between Chinese indigenous and western pig breeds. Here, we surveyed the genome-wide DNA methylation profiles of blood leukocytes from three pig breeds (Tongcheng, Landrace, and Wuzhishan) by methylated DNA immunoprecipitation sequencing. The results showed that DNA methylation was enriched in gene body regions and repetitive sequences. LINE/L1 and SINE/tRNA-Glu were the predominant methylated repeats in pigs. The methylation level in the gene body regions was higher than in the 5′ and 3′ flanking regions of genes. About 15% of CpG islands were methylated in the pig genomes. Additionally, 2,807, 2,969, and 5,547 differentially methylated genes (DMGs) were identified in the Tongcheng vs. Landrace, Tongcheng vs. Wuzhishan, and Landrace vs. Wuzhishan comparisons, respectively. A total of 868 DMGs were shared by the three contrasts. The DMGs were significantly enriched in development- and metabolism-related biological processes and pathways. Finally, we identified 32 candidate DMGs associated with phenotype variance in pigs. Our research provides a DNA methylome resource for pigs and furthers understanding of epigenetically regulated phenotype variance in mammals. PMID:27444743

  14. Genome-wide analysis of DNA methylation in obese, lean, and miniature pig breeds.

    PubMed

    Yang, Yalan; Zhou, Rong; Mu, Yulian; Hou, Xinhua; Tang, Zhonglin; Li, Kui

    2016-01-01

    DNA methylation is a crucial epigenetic modification involved in diverse biological processes. There is significant phenotypic variance between Chinese indigenous and western pig breeds. Here, we surveyed the genome-wide DNA methylation profiles of blood leukocytes from three pig breeds (Tongcheng, Landrace, and Wuzhishan) by methylated DNA immunoprecipitation sequencing. The results showed that DNA methylation was enriched in gene body regions and repetitive sequences. LINE/L1 and SINE/tRNA-Glu were the predominant methylated repeats in pigs. The methylation level in the gene body regions was higher than in the 5' and 3' flanking regions of genes. About 15% of CpG islands were methylated in the pig genomes. Additionally, 2,807, 2,969, and 5,547 differentially methylated genes (DMGs) were identified in the Tongcheng vs. Landrace, Tongcheng vs. Wuzhishan, and Landrace vs. Wuzhishan comparisons, respectively. A total of 868 DMGs were shared by the three contrasts. The DMGs were significantly enriched in development- and metabolism-related biological processes and pathways. Finally, we identified 32 candidate DMGs associated with phenotype variance in pigs. Our research provides a DNA methylome resource for pigs and furthers understanding of epigenetically regulated phenotype variance in mammals. PMID:27444743

  15. Genome wide association study of seedling and adult plant leaf rust resistance in elite spring wheat breeding lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resista...

  16. Genome wide analysis reveals single nucleotide polymorphisms associated with fatness and putative novel copy number variants in three pig breeds

    PubMed Central

    2013-01-01

    Background Obesity, excess fat tissue in the body, can underlie a variety of medical complaints including heart disease, stroke and cancer. The pig is an excellent model organism for the study of various human disorders, including obesity, as well as being the foremost agricultural species. In order to identify genetic variants associated with fatness, we used a selective genomic approach sampling DNA from animals at the extreme ends of the fat and lean spectrum using estimated breeding values derived from a total population size of over 70,000 animals. DNA from 3 breeds (Sire Line Large White, Duroc and a white Pietrain composite line (Titan)) was used to interrogate the Illumina Porcine SNP60 Genotyping Beadchip in order to identify significant associations in terms of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Results By sampling animals at each end of the fat/lean EBV (estimate breeding value) spectrum the whole population could be assessed using less than 300 animals, without losing statistical power. Indeed, several significant SNPs (at the 5% genome wide significance level) were discovered, 4 of these linked to genes with ontologies that had previously been correlated with fatness (NTS, FABP6, SST and NR3C2). Quantitative analysis of the data identified putative CNV regions containing genes whose ontology suggested fatness related functions (MCHR1, PPARα, SLC5A1 and SLC5A4). Conclusions Selective genotyping of EBVs at either end of the phenotypic spectrum proved to be a cost effective means of identifying SNPs and CNVs associated with fatness and with estimated major effects in a large population of animals. PMID:24225222

  17. A genome-wide SNP panel for genetic diversity, mapping and breeding studies in rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome-wide SNP resource was developed for rice using the GoldenGate assay and used to genotype 400 landrace accessions of O. sativa. SNPs were originally discovered using Perlegen re-sequencing technology in 20 diverse landraces of O. sativa as part of OryzaSNP project (http://irfgc.irri.org). An...

  18. Genome Wide Scan for Loci influencing Warner Bratzler Shear Force in Five Bos taurus Breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic tests for beef tenderness are currently limited to single nucleotide polymorphisms (SNPs) within µ-calpain (CAPN1) and calpastatin (CAST) and explain little of the phenotypic variation in Warner-Bratzler shear force (WBSF). We performed a genome-wide association study for WBSF by genotyping...

  19. Singular value decomposition for genome-wide expression data processing and modeling

    PubMed Central

    Alter, Orly; Brown, Patrick O.; Botstein, David

    2000-01-01

    We describe the use of singular value decomposition in transforming genome-wide expression data from genes × arrays space to reduced diagonalized “eigengenes” × “eigenarrays” space, where the eigengenes (or eigenarrays) are unique orthonormal superpositions of the genes (or arrays). Normalizing the data by filtering out the eigengenes (and eigenarrays) that are inferred to represent noise or experimental artifacts enables meaningful comparison of the expression of different genes across different arrays in different experiments. Sorting the data according to the eigengenes and eigenarrays gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype, respectively. After normalization and sorting, the significant eigengenes and eigenarrays can be associated with observed genome-wide effects of regulators, or with measured samples, in which these regulators are overactive or underactive, respectively. PMID:10963673

  20. Quantitative trait loci for rice blast resistance detected in a local rice breeding population by genome-wide association mapping

    PubMed Central

    Shinada, Hiroshi; Yamamoto, Toshio; Sato, Hirokazu; Yamamoto, Eiji; Hori, Kiyosumi; Yonemaru, Junichi; Sato, Takashi; Fujino, Kenji

    2015-01-01

    Plant breeding programs aim to develop cultivars with high adaptability to the specific conditions in a local region. As a result, unique genes and gene combinations have been accumulated in local elite breeding populations during the long history of plant breeding. Genetic analyses on such genes and combinations may be useful for developing new cultivars with more-desirable agronomic traits. Here, we attempted to detect quantitative trait loci (QTL) for rice blast resistance (BR) using a local breeding rice population from Hokkaido, Japan. Using genotyping data on single nucleotide polymorphisms and simple sequence repeat markers distributed throughout the whole genomic region, we detected genetic regions associated with phenotypic variation in BR by a genome-wide association mapping study (GWAS). An additional association analysis using other breeding cultivars verified the effect and inheritance of the associated region. Furthermore, the existence of a gene for BR in the associated region was confirmed by QTL mapping. The results from these studies enabled us to estimate potential of the Hokkaido rice population as a gene pool for improving BR. The results of this study could be useful for developing novel cultivars with vigorous BR in rice breeding programs. PMID:26719741

  1. Genome-Wide Survey of SNP Variation Uncovers the Genetic Structure of Cattle Breeds.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A deep draft sequence assembly derived from shotgun reads from a single Hereford female and comparative sampling sequences from cows representing six additional bovine breeds has enabled the development of genetic probes to interrogate single nucleotide polymorphisms for population and breed analyse...

  2. Enhancing Genome-Wide Copy Number Variation Identification by High Density Array CGH Using Diverse Resources of Pig Breeds

    PubMed Central

    Wang, Jiying; Jiang, Jicai; Wang, Haifei; Kang, Huimin; Zhang, Qin; Liu, Jian-Feng

    2014-01-01

    Copy number variations (CNVs) are important forms of genomic variation, and have attracted extensive attentions in humans as well as domestic animals. In the study, using a custom-designed 2.1 M array comparative genomic hybridization (aCGH), genome-wide CNVs were identified among 12 individuals from diverse pig breeds, including one Asian wild population, six Chinese indigenous breeds and two modern commercial breeds (Yorkshire and Landrace), with one individual of the other modern commercial breed, Duroc, as the reference. A total of 1,344 CNV regions (CNVRs) were identified, covering 47.79 Mb (∼1.70%) of the pig genome. The length of these CNVRs ranged from 3.37 Kb to 1,319.0 Kb with a mean of 35.56 Kb and a median of 11.11 Kb. Compared with similar studies reported, most of the CNVRs (74.18%) were firstly identified in present study. In order to confirm these CNVRs, 21 CNVRs were randomly chosen to be validated by quantitative real time PCR (qPCR) and a high rate (85.71%) of confirmation was obtained. Functional annotation of CNVRs suggested that the identified CNVRs have important function, and may play an important role in phenotypic and production traits difference among various breeds. Our results are essential complementary to the CNV map in the pig genome, which will provide abundant genetic markers to investigate association studies between various phenotypes and CNVs in pigs. PMID:24475311

  3. Genome-Wide Analysis of Positively Selected Genes in Seasonal and Non-Seasonal Breeding Species

    PubMed Central

    Liu, Mingyu; Chen, Junhui; Tian, Shuai; Zhuo, Min; Zhang, Yu; Zhong, Yang; Du, Hongli; Wang, Xiaoning

    2015-01-01

    Some mammals breed throughout the year, while others breed only at certain times of year. These differences in reproductive behavior can be explained by evolution. We identified positively-selected genes in two sets of species with different degrees of relatedness including seasonal and non-seasonal breeding species, using branch-site models. After stringent filtering by sum of pairs scoring, we revealed that more genes underwent positive selection in seasonal compared with non-seasonal breeding species. Positively-selected genes were verified by cDNA mapping of the positive sites with the corresponding cDNA sequences. The design of the evolutionary analysis can effectively lower the false-positive rate and thus identify valid positive genes. Validated, positively-selected genes, including CGA, DNAH1, INVS, and CD151, were related to reproductive behaviors such as spermatogenesis and cell proliferation in non-seasonal breeding species. Genes in seasonal breeding species, including THRAP3, TH1L, and CMTM6, may be related to the evolution of sperm and the circadian rhythm system. Identification of these positively-selected genes might help to identify the molecular mechanisms underlying seasonal and non-seasonal reproductive behaviors. PMID:26000771

  4. Genome-wide association studies based on sequence-derived genotypes reveal new QTL associated with conformation and performance traits in the Franches-Montagnes horse breed.

    PubMed

    Frischknecht, M; Signer-Hasler, H; Leeb, T; Rieder, S; Neuditschko, M

    2016-04-01

    To identify novel quantitative trait loci (QTL) within horses, we performed genome-wide association studies (GWAS) based on sequence-level genotypes for conformation and performance traits in the Franches-Montagnes (FM) horse breed. Sequence-level genotypes of FM horses were derived by re-sequencing 30 key founders and imputing 50K data of genotyped horses. In total, we included 1077 FM horses genotyped for ~4 million SNPs and their respective de-regressed breeding values of the traits in the analysis. Based on this dataset, we identified a total of 14 QTL associated with 18 conformation traits and one performance trait. Therefore, our results suggest that the application of sequence-derived genotypes increases the power to identify novel QTL which were not identified previously based on 50K SNP chip data. PMID:26767322

  5. Genome Wide Association Study of Seedling and Adult Plant Leaf Rust Resistance in Elite Spring Wheat Breeding Lines

    PubMed Central

    Gao, Liangliang; Turner, M. Kathryn; Chao, Shiaoman; Kolmer, James; Anderson, James A.

    2016-01-01

    Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resistance genes or QTLs in 338 spring wheat breeding lines from public and private sectors that were predominately developed in the Americas. A total of 46 QTLs were identified for field and seedling traits and approximately 20–30 confer field resistance in varying degrees. The 10 QTLs accounting for the most variation in field resistance explained 26–30% of the total variation (depending on traits: percent severity, coefficient of infection or response type). Similarly, the 10 QTLs accounting for most of the variation in seedling resistance to different races explained 24–34% of the variation, after correcting for population structure. Two potentially novel QTLs (QLr.umn-1AL, QLr.umn-4AS) were identified. Identification of novel genes or QTLs and validation of previously identified genes or QTLs for seedling and especially adult plant resistance will enhance understanding of leaf rust resistance and assist breeding for resistant wheat varieties. We also developed computer programs to automate field and seedling rust phenotype data conversions. This is the first GWAS study of leaf rust resistance in elite wheat breeding lines genotyped with high density 90K SNP arrays. PMID:26849364

  6. Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

    PubMed Central

    Petersen, Jessica L.; Mickelson, James R.; Rendahl, Aaron K.; Valberg, Stephanie J.; Andersson, Lisa S.; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M.; Borges, Alexandre S.; Brama, Pieter; da Câmara Machado, Artur; Capomaccio, Stefano; Cappelli, Katia; Cothran, E. Gus; Distl, Ottmar; Fox-Clipsham, Laura; Graves, Kathryn T.; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A.; Mikko, Sofia; Orr, Nicholas; Penedo, M. Cecilia T.; Piercy, Richard J.; Raekallio, Marja; Rieder, Stefan; Røed, Knut H.; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; Wade, Claire M.; McCue, Molly E.

    2013-01-01

    Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. PMID:23349635

  7. Genome-wide analysis reveals selection for important traits in domestic horse breeds.

    PubMed

    Petersen, Jessica L; Mickelson, James R; Rendahl, Aaron K; Valberg, Stephanie J; Andersson, Lisa S; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M; Borges, Alexandre S; Brama, Pieter; da Câmara Machado, Artur; Capomaccio, Stefano; Cappelli, Katia; Cothran, E Gus; Distl, Ottmar; Fox-Clipsham, Laura; Graves, Kathryn T; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A; Mikko, Sofia; Orr, Nicholas; Penedo, M Cecilia T; Piercy, Richard J; Raekallio, Marja; Rieder, Stefan; Røed, Knut H; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; Wade, Claire M; McCue, Molly E

    2013-01-01

    Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. PMID:23349635

  8. Population genomic structure and linkage disequilibrium analysis of South African goat breeds using genome-wide SNP data.

    PubMed

    Mdladla, K; Dzomba, E F; Huson, H J; Muchadeyi, F C

    2016-08-01

    The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2)  = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of <150 for all populations 13 generations ago. The estimated correlations for all breed pairs were lower than 0.80 at marker distances >100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in

  9. Genome-wide Association Mapping of Fusarium Head Blight Resistance in Contemporary Barley Breeding Germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilization of quantitative trait loci (QTL) identified in bi-parental mapping populations has had limited success for complex quantitative traits. The use of association mapping in contemporary breeding germplasm may lead to more effective marker strategies for crop improvement. To map Fusarium he...

  10. Genome-wide association study for longevity with whole-genome sequencing in 3 cattle breeds.

    PubMed

    Zhang, Qianqian; Guldbrandtsen, Bernt; Thomasen, Jørn Rind; Lund, Mogens Sandø; Sahana, Goutam

    2016-09-01

    Longevity is an important economic trait in dairy production. Improvements in longevity could increase the average number of lactations per cow, thereby affecting the profitability of the dairy cattle industry. Improved longevity for cows reduces the replacement cost of stock and enables animals to achieve the highest production period. Moreover, longevity is an indirect indicator of animal welfare. Using whole-genome sequencing variants in 3 dairy cattle breeds, we carried out an association study and identified 7 genomic regions in Holstein and 5 regions in Red Dairy Cattle that were associated with longevity. Meta-analyses of 3 breeds revealed 2 significant genomic regions, located on chromosomes 6 (META-CHR6-88MB) and 18 (META-CHR18-58MB). META-CHR6-88MB overlaps with 2 known genes: neuropeptide G-protein coupled receptor (NPFFR2; 89,052,210-89,059,348 bp) and vitamin D-binding protein precursor (GC; 88,695,940-88,739,180 bp). The NPFFR2 gene was previously identified as a candidate gene for mastitis resistance. META-CHR18-58MB overlaps with zinc finger protein 717 (ZNF717; 58,130,465-58,141,877 bp) and zinc finger protein 613 (ZNF613; 58,115,782-58,117,110 bp), which have been associated with calving difficulties. Information on longevity-associated genomic regions could be used to find causal genes/variants influencing longevity and exploited to improve the reliability of genomic prediction. PMID:27289149

  11. A validated genome wide association study to breed cattle adapted to an environment altered by climate change.

    PubMed

    Hayes, Ben J; Bowman, Phil J; Chamberlain, Amanda J; Savin, Keith; van Tassell, Curt P; Sonstegard, Tad S; Goddard, Mike E

    2009-01-01

    Continued production of food in areas predicted to be most affected by climate change, such as dairy farming regions of Australia, will be a major challenge in coming decades. Along with rising temperatures and water shortages, scarcity of inputs such as high energy feeds is predicted. With the motivation of selecting cattle adapted to these changing environments, we conducted a genome wide association study to detect DNA markers (single nucleotide polymorphisms) associated with the sensitivity of milk production to environmental conditions. To do this we combined historical milk production and weather records with dense marker genotypes on dairy sires with many daughters milking across a wide range of production environments in Australia. Markers associated with sensitivity of milk production to feeding level and sensitivity of milk production to temperature humidity index on chromosome nine and twenty nine respectively were validated in two independent populations, one a different breed of cattle. As the extent of linkage disequilibrium across cattle breeds is limited, the underlying causative mutations have been mapped to a small genomic interval containing two promising candidate genes. The validated marker panels we have reported here will aid selection for high milk production under anticipated climate change scenarios, for example selection of sires whose daughters will be most productive at low levels of feeding. PMID:19688089

  12. Diversifying Selection Between Pure-Breed and Free-Breeding Dogs Inferred from Genome-Wide SNP Analysis

    PubMed Central

    Pilot, Małgorzata; Malewski, Tadeusz; Moura, Andre E.; Grzybowski, Tomasz; Oleński, Kamil; Kamiński, Stanisław; Fadel, Fernanda Ruiz; Alagaili, Abdulaziz N.; Mohammed, Osama B.; Bogdanowicz, Wiesław

    2016-01-01

    Domesticated species are often composed of distinct populations differing in the character and strength of artificial and natural selection pressures, providing a valuable model to study adaptation. In contrast to pure-breed dogs that constitute artificially maintained inbred lines, free-ranging dogs are typically free-breeding, i.e., unrestrained in mate choice. Many traits in free-breeding dogs (FBDs) may be under similar natural and sexual selection conditions to wild canids, while relaxation of sexual selection is expected in pure-breed dogs. We used a Bayesian approach with strict false-positive control criteria to identify FST-outlier SNPs between FBDs and either European or East Asian breeds, based on 167,989 autosomal SNPs. By identifying outlier SNPs located within coding genes, we found four candidate genes under diversifying selection shared by these two comparisons. Three of them are associated with the Hedgehog (HH) signaling pathway regulating vertebrate morphogenesis. A comparison between FBDs and East Asian breeds also revealed diversifying selection on the BBS6 gene, which was earlier shown to cause snout shortening and dental crowding via disrupted HH signaling. Our results suggest that relaxation of natural and sexual selection in pure-breed dogs as opposed to FBDs could have led to mild changes in regulation of the HH signaling pathway. HH inhibits adhesion and the migration of neural crest cells from the neural tube, and minor deficits of these cells during embryonic development have been proposed as the underlying cause of “domestication syndrome.” This suggests that the process of breed formation involved the same genetic and developmental pathways as the process of domestication. PMID:27233669

  13. Diversifying Selection Between Pure-Breed and Free-Breeding Dogs Inferred from Genome-Wide SNP Analysis.

    PubMed

    Pilot, Małgorzata; Malewski, Tadeusz; Moura, Andre E; Grzybowski, Tomasz; Oleński, Kamil; Kamiński, Stanisław; Fadel, Fernanda Ruiz; Alagaili, Abdulaziz N; Mohammed, Osama B; Bogdanowicz, Wiesław

    2016-01-01

    Domesticated species are often composed of distinct populations differing in the character and strength of artificial and natural selection pressures, providing a valuable model to study adaptation. In contrast to pure-breed dogs that constitute artificially maintained inbred lines, free-ranging dogs are typically free-breeding, i.e., unrestrained in mate choice. Many traits in free-breeding dogs (FBDs) may be under similar natural and sexual selection conditions to wild canids, while relaxation of sexual selection is expected in pure-breed dogs. We used a Bayesian approach with strict false-positive control criteria to identify FST-outlier SNPs between FBDs and either European or East Asian breeds, based on 167,989 autosomal SNPs. By identifying outlier SNPs located within coding genes, we found four candidate genes under diversifying selection shared by these two comparisons. Three of them are associated with the Hedgehog (HH) signaling pathway regulating vertebrate morphogenesis. A comparison between FBDs and East Asian breeds also revealed diversifying selection on the BBS6 gene, which was earlier shown to cause snout shortening and dental crowding via disrupted HH signaling. Our results suggest that relaxation of natural and sexual selection in pure-breed dogs as opposed to FBDs could have led to mild changes in regulation of the HH signaling pathway. HH inhibits adhesion and the migration of neural crest cells from the neural tube, and minor deficits of these cells during embryonic development have been proposed as the underlying cause of "domestication syndrome." This suggests that the process of breed formation involved the same genetic and developmental pathways as the process of domestication. PMID:27233669

  14. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  15. Genome-wide Association Study of Integrated Meat Quality-related Traits of the Duroc Pig Breed.

    PubMed

    Lee, Taeheon; Shin, Dong-Hyun; Cho, Seoae; Kang, Hyun Sung; Kim, Sung Hoon; Lee, Hak-Kyo; Kim, Heebal; Seo, Kang-Seok

    2014-03-01

    The increasing importance of meat quality has implications for animal breeding programs. Research has revealed much about the genetic background of pigs, and many studies have revealed the importance of various genetic factors. Since meat quality is a complex trait which is affected by many factors, consideration of the overall phenotype is very useful to study meat quality. For integrating the phenotypes, we used principle component analysis (PCA). The significant SNPs refer to results of the GRAMMAR method against PC1, PC2 and PC3 of 14 meat quality traits of 181 Duroc pigs. The Genome-wide association study (GWAS) found 26 potential SNPs affecting various meat quality traits. The loci identified are located in or near 23 genes. The SNPs associated with meat quality are in or near five genes (ANK1, BMP6, SHH, PIP4K2A, and FOXN2) and have been reported previously. Twenty-five of the significant SNPs also located in meat quality-related QTL regions, these result supported the QTL effect indirectly. Each single gene typically affects multiple traits. Therefore, it is a useful approach to use integrated traits for the various traits at the same time. This innovative approach using integrated traits could be applied on other GWAS of complex-traits including meat-quality, and the results will contribute to improving meat-quality of pork. PMID:25049955

  16. Genome-Wide Association Mapping for Yield and Other Agronomic Traits in an Elite Breeding Population of Tropical Rice (Oryza sativa)

    PubMed Central

    Lalusin, Antonio; Borromeo, Teresita; Gregorio, Glenn; Hernandez, Jose; Virk, Parminder; Collard, Bertrand; McCouch, Susan R.

    2015-01-01

    Genome-wide association mapping studies (GWAS) are frequently used to detect QTL in diverse collections of crop germplasm, based on historic recombination events and linkage disequilibrium across the genome. Generally, diversity panels genotyped with high density SNP panels are utilized in order to assay a wide range of alleles and haplotypes and to monitor recombination breakpoints across the genome. By contrast, GWAS have not generally been performed in breeding populations. In this study we performed association mapping for 19 agronomic traits including yield and yield components in a breeding population of elite irrigated tropical rice breeding lines so that the results would be more directly applicable to breeding than those from a diversity panel. The population was genotyped with 71,710 SNPs using genotyping-by-sequencing (GBS), and GWAS performed with the explicit goal of expediting selection in the breeding program. Using this breeding panel we identified 52 QTL for 11 agronomic traits, including large effect QTLs for flowering time and grain length/grain width/grain-length-breadth ratio. We also identified haplotypes that can be used to select plants in our population for short stature (plant height), early flowering time, and high yield, and thus demonstrate the utility of association mapping in breeding populations for informing breeding decisions. We conclude by exploring how the newly identified significant SNPs and insights into the genetic architecture of these quantitative traits can be leveraged to build genomic-assisted selection models. PMID:25785447

  17. Genome-wide analysis of Italian sheep diversity reveals a strong geographic pattern and cryptic relationships between breeds.

    PubMed

    Ciani, E; Crepaldi, P; Nicoloso, L; Lasagna, E; Sarti, F M; Moioli, B; Napolitano, F; Carta, A; Usai, G; D'Andrea, M; Marletta, D; Ciampolini, R; Riggio, V; Occidente, M; Matassino, D; Kompan, D; Modesto, P; Macciotta, N; Ajmone-Marsan, P; Pilla, F

    2014-04-01

    Italy counts several sheep breeds, arisen over centuries as a consequence of ancient and recent genetic and demographic events. To finely reconstruct genetic structure and relationships between Italian sheep, 496 subjects from 19 breeds were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds from the Sheep HapMap dataset was also included in the analyses. Genetic distances (as visualized either in a network or in a multidimensional scaling analysis of identical by state distances) closely reflected geographic proximity between breeds, with a clear north-south gradient, likely because of high levels of past gene flow and admixture all along the peninsula. Sardinian breeds diverged more from other breeds, a probable consequence of the combined effect of ancient sporadic introgression of feral mouflon and long-lasting genetic isolation from continental sheep populations. The study allowed the detection of previously undocumented episodes of recent introgression (Delle Langhe into the endangered Altamurana breed) as well as signatures of known, or claimed, historical introgression (Merino into Sopravissana and Gentile di Puglia; Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese). Arguments that would question, from a genomic point of view, the current breed classification of Bergamasca and Biellese into two separate breeds are presented. Finally, a role for traditional transhumance practices in shaping the genetic makeup of Alpine sheep breeds is proposed. The study represents the first exhaustive analysis of Italian sheep diversity in an European context, and it bridges the gap in the previous HapMap panel between Western Mediterranean and Swiss breeds. PMID:24303943

  18. The Shepherds’ Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds

    PubMed Central

    Ljungvall, Ingrid; Merveille, Anne-Christine; Gouni, Vassiliki; Wiberg, Maria; Lundgren Willesen, Jakob; Hanås, Sofia; Lequarré, Anne-Sophie; Mejer Sørensen, Louise; Tiret, Laurent; McEntee, Kathleen; Seppälä, Eija; Koch, Jørgen; Battaille, Géraldine; Lohi, Hannes; Fredholm, Merete; Chetboul, Valerie; Häggström, Jens; Carlborg, Örjan; Lindblad-Toh, Kerstin; Höglund, Katja

    2015-01-01

    Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus. PMID:25970163

  19. Effect of population size and unbalanced data sets on QTL detection using genome-wide association mapping in barley breeding germplasm.

    PubMed

    Wang, Hongyun; Smith, Kevin P; Combs, Emily; Blake, Tom; Horsley, Richard D; Muehlbauer, Gary J

    2012-01-01

    Over the past two decades many quantitative trait loci (QTL) have been detected; however, very few have been incorporated into breeding programs. The recent development of genome-wide association studies (GWAS) in plants provides the opportunity to detect QTL in germplasm collections such as unstructured populations from breeding programs. The overall goal of the barley Coordinated Agricultural Project was to conduct GWAS with the intent to couple QTL detection and breeding. The basic idea is that breeding programs generate a vast amount of phenotypic data and combined with cheap genotyping it should be possible to use GWAS to detect QTL that would be immediately accessible and used by breeding programs. There are several constraints to using breeding program-derived phenotype data for conducting GWAS namely: limited population size and unbalanced data sets. We chose the highly heritable trait heading date to study these two variables. We examined 766 spring barley breeding lines (panel #1) grown in balanced trials and a subset of 384 spring barley breeding lines (panel #2) grown in balanced and unbalanced trials. In panel #1, we detected three major QTL for heading date that have been detected in previous bi-parental mapping studies. Simulation studies showed that population sizes greater than 384 individuals are required to consistently detect QTL. We also showed that unbalanced data sets from panel #2 can be used to detect the three major QTL. However, unbalanced data sets resulted in an increase in the false-positive rate. Interestingly, one-step analysis performed better than two-step analysis in reducing the false-positive rate. The results of this work show that it is possible to use phenotypic data from breeding programs to detect QTL, but that careful consideration of population size and experimental design are required. PMID:21898052

  20. A genome-wide association study to detect genetic variation for postpartum dysgalactia syndrome in five commercial pig breeding lines.

    PubMed

    Preissler, Regine; Tetens, Jens; Reiners, Kerstin; Looft, Holger; Kemper, Nicole

    2013-08-01

    Postpartum dysgalactia syndrome (PDS) in sows is an important disease after parturition with a relevant economic impact, affecting the health and welfare of both sows and piglets. The genetic background of this disease has been discussed and its heritability estimated, but further genetic analyses are lacking in detail. The aim of the current study was to detect loci affecting the susceptibility to PDS through a genome-wide association approach. The study was designed as a family-based association study with matched sampling of affected sows and healthy half- or full-sib control sows on six farms. For the study, 597 sows (322 affected vs. 275 healthy control sows) were genotyped on 62 163 single nucleotide polymorphisms (SNPs) using the Illumina PorcineSNP60 BeadChip. After quality control, 585 sows (314 affected vs. 271 healthy control sows) and 49 740 SNPs remained for further analysis. Statistics were performed mainly with the r package genabel and included a principal component analysis. A statistically significant genome-wide associated SNP was identified on porcine chromosome (SSC) 17. Further promising results with moderate significance were detected on SSC 13 and on an unplaced scaffold with an older annotation on SSC 15. The PRICKLE2 and NRP2 genes were identified as candidate genes near associated SNPs. Several quantitative trait loci (QTL) have been previously described in these genomic regions, including QTL for mammary gland condition, as teat number and non-functional nipples QTL, as well as QTL for body temperature and gestation length. PMID:23742276

  1. A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12

    PubMed Central

    Massey, Jonathan; Dietschi, Elisabeth; Kierczak, Marcin; Lund-Ziener, Martine; Sundberg, Katarina; Thoresen, Stein Istre; Kämpe, Olle; Andersson, Göran; Ollier, William E. R.; Hedhammar, Åke; Leeb, Tosso; Lindblad-Toh, Kerstin; Kennedy, Lorna J.; Lingaas, Frode; Rosengren Pielberg, Gerli

    2015-01-01

    Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans. PMID:26261983

  2. Genome-wide assessment of worldwide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breed utilization, genetic improvement, and industry consolidation are predicted to have major impacts on the genetic composition of commercial chickens. Consequently, the question arises as to whether sufficient genetic diversity remains within industry stocks to address future needs. With the ch...

  3. Genome-wide study on intramuscular fat in Italian Large White pig breed using the PorcineSNP60 BeadChip.

    PubMed

    Davoli, R; Luise, D; Mingazzini, V; Zambonelli, P; Braglia, S; Serra, A; Russo, V

    2016-08-01

    Genome-wide association study results are presented for intramuscular fat in Italian Large White pig breed. A total of 886 individuals were genotyped with PorcineSNP60 BeadChip. After quality control performed with plink software and in R environment, 49 208 markers remained for the association analysis. The genome-wide association studies was conducted using linear mixed model implemented in GenABEL. We detected seven new SNPs of genes till now not found associated to intramuscular fat (IMF). Three markers map in a wide intergenic region rich of QTL linked to fat traits, one map 388 kb upstream the gene SDK1, one map inside PPP3CA gene, one inside SCPEP1 gene and the last is not mapped in the porcine genome yet. Associations here presented indicate a moderate effect of these genes on IMF. In particular, PPP3CA, that is involved in the oxidative metabolism of skeletal muscle, could be considerated as an interesting candidate gene for IMF content in pigs. However, further studies are needed to clarify the role of these genes on the physiological processes involved in IMF regulation. These results may be useful to control this trait that is important in terms of nutritional, technological and organoleptic characteristics of fresh meat and processed products. PMID:26578072

  4. Genome-wide assessment of worldwide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds

    PubMed Central

    Muir, William M.; Wong, Gane Ka-Shu; Zhang, Yong; Wang, Jun; Groenen, Martien A. M.; Crooijmans, Richard P. M. A.; Megens, Hendrik-Jan; Zhang, Huanmin; Okimoto, Ron; Vereijken, Addie; Jungerius, Annemieke; Albers, Gerard A. A.; Lawley, Cindy Taylor; Delany, Mary E.; MacEachern, Sean; Cheng, Hans H.

    2008-01-01

    Breed utilization, genetic improvement, and industry consolidation are predicted to have major impacts on the genetic composition of commercial chickens. Consequently, the question arises as to whether sufficient genetic diversity remains within industry stocks to address future needs. With the chicken genome sequence and more than 2.8 million single-nucleotide polymorphisms (SNPs), it is now possible to address biodiversity using a previously unattainable metric: missing alleles. To achieve this assessment, 2551 informative SNPs were genotyped on 2580 individuals, including 1440 commercial birds. The proportion of alleles lacking in commercial populations was assessed by (1) estimating the global SNP allele frequency distribution from a hypothetical ancestral population as a reference, then determining the portion of the distribution lost, and then (2) determining the relationship between allele loss and the inbreeding coefficient. The results indicate that 50% or more of the genetic diversity in ancestral breeds is absent in commercial pure lines. The missing genetic diversity resulted from the limited number of incorporated breeds. As such, hypothetically combining stocks within a company could recover only preexisting within-breed variability, but not more rare ancestral alleles. We establish that SNP weights act as sentinels of biodiversity and provide an objective assessment of the strains that are most valuable for preserving genetic diversity. This is the first experimental analysis investigating the extant genetic diversity of virtually an entire agricultural commodity. The methods presented are the first to characterize biodiversity in terms of allelic diversity and to objectively link rate of allele loss with the inbreeding coefficient. PMID:18981413

  5. Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH)

    PubMed Central

    Velie, Brandon D.; Shrestha, Merina; Franҫois, Liesbeth; Schurink, Anouk; Tesfayonas, Yohannes G.; Stinckens, Anneleen; Blott, Sarah; Ducro, Bart J.; Mikko, Sofia; Thomas, Ruth; Swinburne, June E.; Sundqvist, Marie; Eriksson, Susanne; Buys, Nadine; Lindgren, Gabriella

    2016-01-01

    While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions. PMID:27070818

  6. Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH).

    PubMed

    Velie, Brandon D; Shrestha, Merina; Franҫois, Liesbeth; Schurink, Anouk; Tesfayonas, Yohannes G; Stinckens, Anneleen; Blott, Sarah; Ducro, Bart J; Mikko, Sofia; Thomas, Ruth; Swinburne, June E; Sundqvist, Marie; Eriksson, Susanne; Buys, Nadine; Lindgren, Gabriella

    2016-01-01

    While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions. PMID:27070818

  7. Genome-wide insertion-deletion (InDel) marker discovery and genotyping for genomics-assisted breeding applications in chickpea.

    PubMed

    Das, Shouvik; Upadhyaya, Hari D; Srivastava, Rishi; Bajaj, Deepak; Gowda, C L L; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K; Parida, Swarup K

    2015-10-01

    We developed 21,499 genome-wide insertion-deletion (InDel) markers (2- to 54-bp in silico fragment length polymorphism) by comparing the genomic sequences of four (desi, kabuli and wild C. reticulatum) chickpea [Cicer arietinum (L.)] accessions. InDel markers showing 2- to 6-bp fragment length polymorphism among accessions were abundant (76.8%) in the chickpea genome. The physically mapped 7,643 and 13,856 markers on eight chromosomes and unanchored scaffolds, respectively, were structurally and functionally annotated. The 4,506 coding (23% large-effect frameshift mutations) and regulatory InDel markers were identified from 3,228 genes (representing 11.7% of total 27,571 desi genes), suggesting their functional relevance for trait association/genetic mapping. High amplification (97%) and intra-specific polymorphic (60-83%) potential and wider genetic diversity (15-89%) were detected by genome-wide 6,254 InDel markers among desi, kabuli and wild accessions using even a simpler cost-effective agarose gel-based assay. This signifies added advantages of this user-friendly genetic marker system for manifold large-scale genotyping applications in laboratories with limited infrastructure and resources. Utilizing 6,254 InDel markers-based high-density (inter-marker distance: 0.212 cM) inter-specific genetic linkage map (ICC 4958 × ICC 17160) of chickpea as a reference, three major genomic regions harboring six flowering and maturity time robust QTLs (16.4-27.5% phenotypic variation explained, 8.1-11.5 logarithm of odds) were identified. Integration of genetic and physical maps at these target QTL intervals mapped on three chromosomes delineated five InDel markers-containing candidate genes tightly linked to the QTLs governing flowering and maturity time in chickpea. Taken together, our study demonstrated the practical utility of developing and high-throughput genotyping of such beneficial InDel markers at a genome-wide scale to expedite genomics-assisted breeding

  8. Genome-wide insertion–deletion (InDel) marker discovery and genotyping for genomics-assisted breeding applications in chickpea

    PubMed Central

    Das, Shouvik; Upadhyaya, Hari D.; Srivastava, Rishi; Bajaj, Deepak; Gowda, C.L.L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    We developed 21,499 genome-wide insertion–deletion (InDel) markers (2- to 54-bp in silico fragment length polymorphism) by comparing the genomic sequences of four (desi, kabuli and wild C. reticulatum) chickpea [Cicer arietinum (L.)] accessions. InDel markers showing 2- to 6-bp fragment length polymorphism among accessions were abundant (76.8%) in the chickpea genome. The physically mapped 7,643 and 13,856 markers on eight chromosomes and unanchored scaffolds, respectively, were structurally and functionally annotated. The 4,506 coding (23% large-effect frameshift mutations) and regulatory InDel markers were identified from 3,228 genes (representing 11.7% of total 27,571 desi genes), suggesting their functional relevance for trait association/genetic mapping. High amplification (97%) and intra-specific polymorphic (60–83%) potential and wider genetic diversity (15–89%) were detected by genome-wide 6,254 InDel markers among desi, kabuli and wild accessions using even a simpler cost-effective agarose gel-based assay. This signifies added advantages of this user-friendly genetic marker system for manifold large-scale genotyping applications in laboratories with limited infrastructure and resources. Utilizing 6,254 InDel markers-based high-density (inter-marker distance: 0.212 cM) inter-specific genetic linkage map (ICC 4958 × ICC 17160) of chickpea as a reference, three major genomic regions harboring six flowering and maturity time robust QTLs (16.4–27.5% phenotypic variation explained, 8.1–11.5 logarithm of odds) were identified. Integration of genetic and physical maps at these target QTL intervals mapped on three chromosomes delineated five InDel markers-containing candidate genes tightly linked to the QTLs governing flowering and maturity time in chickpea. Taken together, our study demonstrated the practical utility of developing and high-throughput genotyping of such beneficial InDel markers at a genome-wide scale to expedite genomics

  9. Genome-Wide Study of Structural Variants in Bovine Holstein, Montbéliarde and Normande Dairy Breeds

    PubMed Central

    Boussaha, Mekki; Esquerré, Diane; Barbieri, Johanna; Djari, Anis; Pinton, Alain; Letaief, Rabia; Salin, Gérald; Escudié, Frédéric; Roulet, Alain; Fritz, Sébastien; Samson, Franck; Grohs, Cécile; Bernard, Maria; Klopp, Christophe; Boichard, Didier; Rocha, Dominique

    2015-01-01

    High-throughput sequencing technologies have offered in recent years new opportunities to study genome variations. These studies have mostly focused on single nucleotide polymorphisms, small insertions or deletions and on copy number variants. Other structural variants, such as large insertions or deletions, tandem duplications, translocations, and inversions are less well-studied, despite that some have an important impact on phenotypes. In the present study, we performed a large-scale survey of structural variants in cattle. We report the identification of 6,426 putative structural variants in cattle extracted from whole-genome sequence data of 62 bulls representing the three major French dairy breeds. These genomic variants affect DNA segments greater than 50 base pairs and correspond to deletions, inversions and tandem duplications. Out of these, we identified a total of 547 deletions and 410 tandem duplications which could potentially code for CNVs. Experimental validation was carried out on 331 structural variants using a novel high-throughput genotyping method. Out of these, 255 structural variants (77%) generated good quality genotypes and 191 (75%) of them were validated. Gene content analyses in structural variant regions revealed 941 large deletions removing completely one or several genes, including 10 single-copy genes. In addition, some of the structural variants are located within quantitative trait loci for dairy traits. This study is a pan-genome assessment of genomic variations in cattle and may provide a new glimpse into the bovine genome architecture. Our results may also help to study the effects of structural variants on gene expression and consequently their effect on certain phenotypes of interest. PMID:26317361

  10. Genome-Wide Scan for Visceral Leishmaniasis in Mixed-Breed Dogs Identifies Candidate Genes Involved in T Helper Cells and Macrophage Signaling

    PubMed Central

    Utsunomiya, Yuri T.; Ribeiro, Érica S.; Quintal, Amanda P. N.; Sangalli, Juliano R.; Gazola, Valquiria R.; Paula, Henrique B.; Trinconi, Cristiana M.; Lima, Valéria M. F.; Perri, Silvia H. V.; Taylor, Jeremy F.; Schnabel, Robert D.; Sonstegard, Tad S.; Garcia, José F.; Nunes, Cáris M.

    2015-01-01

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2. The positional association on chromosome 2 mapped to a predicted DNAse sensitive site in CD14+ monocytes that serve as a cis-regulatory element for the expression of interleukin alpha receptors 2 (IL2RA) and 15 (IL15RA). Both interleukins were previously found to lead to protective T helper 1 cell (Th1) response against Leishmania spp. in humans and mice. The associated marker on chromosome 1 was located between two predicted transcription factor binding sites regulating the expression of the transducin-like enhancer of split 1 gene (TLE1), an important player in Notch signaling. This pathway is critical for macrophage activity and CD4+ T cell differentiation into Th1 and T helper 2. Together, these findings suggest that the human and mouse model for protective response against Leishmania spp., which involves Th1 and macrophage modulation by interleukins 2, 15, gamma interferon and Notch signaling, may also hold for the canine model. PMID:26348501

  11. Cassava Breeding I: The Value of Breeding Value

    PubMed Central

    Ceballos, Hernán; Pérez, Juan C.; Joaqui Barandica, Orlando; Lenis, Jorge I.; Morante, Nelson; Calle, Fernando; Pino, Lizbeth; Hershey, Clair H.

    2016-01-01

    Breeding cassava relies on several selection stages (single row trial-SRT; preliminary; advanced; and uniform yield trials—UYT). This study uses data from 14 years of evaluations. From more than 20,000 genotypes initially evaluated only 114 reached the last stage. The objective was to assess how the data at SRT could be used to predict the probabilities of genotypes reaching the UYT. Phenotypic data from each genotype at SRT was integrated into the selection index (SIN) used by the cassava breeding program. Average SIN from all the progenies derived from each progenitor was then obtained. Average SIN is an approximation of the breeding value of each progenitor. Data clearly suggested that some genotypes were better progenitors than others (e.g., high number of their progenies reaching the UYT), suggesting important variation in breeding values of progenitors. However, regression of average SIN of each parental genotype on the number of their respective progenies reaching UYT resulted in a negligible coefficient of determination (r2 = 0.05). Breeding value (e.g., average SIN) at SRT was not efficient predicting which genotypes were more likely to reach the UYT stage. Number of families and progenies derived from a given progenitor were more efficient predicting the probabilities of the progeny from a given parent reaching the UYT stage. Large within-family genetic variation tends to mask the true breeding value of each progenitor. The use of partially inbred progenitors (e.g., S1 or S2 genotypes) would reduce the within-family genetic variation thus making the assessment of breeding value more accurate. Moreover, partial inbreeding of progenitors can improve the breeding value of the original (S0) parental material and sharply accelerate genetic gains. For instance, homozygous S1 genotypes for the dominant resistance to cassava mosaic disease (CMD) could be generated and selected. All gametes from these selected S1 genotypes would carry the desirable allele and

  12. Cassava Breeding I: The Value of Breeding Value.

    PubMed

    Ceballos, Hernán; Pérez, Juan C; Joaqui Barandica, Orlando; Lenis, Jorge I; Morante, Nelson; Calle, Fernando; Pino, Lizbeth; Hershey, Clair H

    2016-01-01

    Breeding cassava relies on several selection stages (single row trial-SRT; preliminary; advanced; and uniform yield trials-UYT). This study uses data from 14 years of evaluations. From more than 20,000 genotypes initially evaluated only 114 reached the last stage. The objective was to assess how the data at SRT could be used to predict the probabilities of genotypes reaching the UYT. Phenotypic data from each genotype at SRT was integrated into the selection index (SIN) used by the cassava breeding program. Average SIN from all the progenies derived from each progenitor was then obtained. Average SIN is an approximation of the breeding value of each progenitor. Data clearly suggested that some genotypes were better progenitors than others (e.g., high number of their progenies reaching the UYT), suggesting important variation in breeding values of progenitors. However, regression of average SIN of each parental genotype on the number of their respective progenies reaching UYT resulted in a negligible coefficient of determination (r (2) = 0.05). Breeding value (e.g., average SIN) at SRT was not efficient predicting which genotypes were more likely to reach the UYT stage. Number of families and progenies derived from a given progenitor were more efficient predicting the probabilities of the progeny from a given parent reaching the UYT stage. Large within-family genetic variation tends to mask the true breeding value of each progenitor. The use of partially inbred progenitors (e.g., S1 or S2 genotypes) would reduce the within-family genetic variation thus making the assessment of breeding value more accurate. Moreover, partial inbreeding of progenitors can improve the breeding value of the original (S0) parental material and sharply accelerate genetic gains. For instance, homozygous S1 genotypes for the dominant resistance to cassava mosaic disease (CMD) could be generated and selected. All gametes from these selected S1 genotypes would carry the desirable allele and

  13. Genome-wide DNA methylation profiling in triple-negative breast cancer reveals epigenetic signatures with important clinical value

    PubMed Central

    Stirzaker, Clare; Zotenko, Elena; Clark, Susan J

    2016-01-01

    abstract Analysis of cancer methylomes has dramatically changed our concept of the potential of diagnostic and prognostic methylation biomarkers in disease stratification. Through whole-genome methylation capture sequencing of triple-negative breast cancers (TNBCs) we recently identified differentially methylated regions with diagnostic and prognostic value that promise to stratify TNBCs for more personalized management. PMID:27308556

  14. Genome-wide DNA methylation profiling in triple-negative breast cancer reveals epigenetic signatures with important clinical value.

    PubMed

    Stirzaker, Clare; Zotenko, Elena; Clark, Susan J

    2016-01-01

    Analysis of cancer methylomes has dramatically changed our concept of the potential of diagnostic and prognostic methylation biomarkers in disease stratification. Through whole-genome methylation capture sequencing of triple-negative breast cancers (TNBCs) we recently identified differentially methylated regions with diagnostic and prognostic value that promise to stratify TNBCs for more personalized management. PMID:27308556

  15. Genome-wide differential expression of genes and small RNAs in testis of two different porcine breeds and at two different ages.

    PubMed

    Li, Yao; Li, Jialian; Fang, Chengchi; Shi, Liang; Tan, Jiajian; Xiong, Yuanzhu; Bin Fan; Li, Changchun

    2016-01-01

    Some documented evidences proved small RNAs (sRNA) and targeted genes are involved in mammalian testicular development and spermatogenesis. However, the detailed molecular regulation mechanisms of them remain largely unknown so far. In this study, we obtained a total of 10,716 mRNAs, 67 miRNAs and 16,953 piRNAs which were differentially expressed between LC and LW pig breeds or between the two sexual maturity stages. Of which, we identified 16 miRNAs and 28 targeted genes possibly related to spermatogenesis; 14 miRNA and 18 targeted genes probably associated with cell adhesion related testis development. We also annotated 579 piRNAs which could potentially regulate cell death, nucleosome organization and other basic biology process, which implied that those piRNAs might be involved in sexual maturation difference. The integrated network analysis results suggested that some differentially expressed genes were involved in spermatogenesis through the ECM-receptor interaction, focal adhesion, Wnt and PI3K-Akt signaling pathways, some particular miRNAs have the negative regulation roles and some special piRNAs have the positive and negative regulation roles in testicular development. Our data provide novel insights into the molecular expression and regulation similarities and diversities of spermatogenesis and testicular development in different pig breeds at different stages of sexual maturity. PMID:27229484

  16. Genome-wide differential expression of genes and small RNAs in testis of two different porcine breeds and at two different ages

    PubMed Central

    Li, Yao; Li, Jialian; Fang, Chengchi; Shi, Liang; Tan, Jiajian; Xiong, Yuanzhu; Bin Fan; Li, Changchun

    2016-01-01

    Some documented evidences proved small RNAs (sRNA) and targeted genes are involved in mammalian testicular development and spermatogenesis. However, the detailed molecular regulation mechanisms of them remain largely unknown so far. In this study, we obtained a total of 10,716 mRNAs, 67 miRNAs and 16,953 piRNAs which were differentially expressed between LC and LW pig breeds or between the two sexual maturity stages. Of which, we identified 16 miRNAs and 28 targeted genes possibly related to spermatogenesis; 14 miRNA and 18 targeted genes probably associated with cell adhesion related testis development. We also annotated 579 piRNAs which could potentially regulate cell death, nucleosome organization and other basic biology process, which implied that those piRNAs might be involved in sexual maturation difference. The integrated network analysis results suggested that some differentially expressed genes were involved in spermatogenesis through the ECM–receptor interaction, focal adhesion, Wnt and PI3K–Akt signaling pathways, some particular miRNAs have the negative regulation roles and some special piRNAs have the positive and negative regulation roles in testicular development. Our data provide novel insights into the molecular expression and regulation similarities and diversities of spermatogenesis and testicular development in different pig breeds at different stages of sexual maturity. PMID:27229484

  17. Prediction of total genetic value using genome-wide dense marker in Holstein breed by Bayesian method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marker-assisted selection (MAS) can be based on molecular markers in linkage equilibrium with quantitative trait loci, molecular markers in linkage disequilibrium with QTL, or on selection of the actual mutations causing the QTL effect. However, one problem in relation to all of them is that only a ...

  18. Genome-Wide Gene Expression Profiles in Lung Tissues of Pig Breeds Differing in Resistance to Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Zhang, Chenhua; Zhang, Yujie; Wang, Nan; Li, Yanping; Yang, Lijuan; Jiang, Chenglan; Zhang, Chaoyang; Wen, Changhong; Jiang, Yunliang

    2014-01-01

    Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is an infectious disease characterized by severe reproductive deficiency in pregnant sows, typical respiratory symptoms in piglets, and high mortality rate of piglets. In this study, we employed an Affymetrix microarray chip to compare the gene expression profiles of lung tissue samples from Dapulian (DPL) pigs (a Chinese indigenous pig breed) and Duroc×Landrace×Yorkshire (DLY) pigs after infection with PRRSV. During infection with PRRSV, the DLY pigs exhibited a range of clinical features that typify the disease, whereas the DPL pigs showed only mild signs of the disease. Overall, the DPL group had a lower percentage of CD4+ cells and lower CD4+/CD8+ratios than the DLY group (p<0.05). For both IL-10 and TNF-α, the DLY pigs had significantly higher levels than the DPL pigs (p<0.01). The DLY pigs have lower serum IFN-γ levels than the DPL pigs (p<0.01). The serum IgG levels increased slightly from 0 dpi to 7 dpi, and peaked at 14 dpi (p<0.0001). Microarray data analysis revealed 16 differentially expressed (DE) genes in the lung tissue samples from the DLY and DPL pigs (q≤5%), of which LOC100516029 and LOC100523005 were up-regulated in the PRRSV-infected DPL pigs, while the other 14 genes were down-regulated in the PRRSV-infected DPL pigs compared with the PRRSV-infected DLY pigs. The mRNA expression levels of 10 out of the 16 DE genes were validated by real-time quantitative RT-PCR and their fold change was consistent with the result of microarray data analysis. We further analyzed the mRNA expression level of 8 differentially expressed genes between the DPL and DLY pigs for both uninfected and infected groups, and found that TF and USP18 genes were important in underlying porcine resistance or susceptibility to PRRSV. PMID:24465897

  19. Comparison of molecular breeding values based on within- and across-breed training in beef cattle

    PubMed Central

    2013-01-01

    Background Although the efficacy of genomic predictors based on within-breed training looks promising, it is necessary to develop and evaluate across-breed predictors for the technology to be fully applied in the beef industry. The efficacies of genomic predictors trained in one breed and utilized to predict genetic merit in differing breeds based on simulation studies have been reported, as have the efficacies of predictors trained using data from multiple breeds to predict the genetic merit of purebreds. However, comparable studies using beef cattle field data have not been reported. Methods Molecular breeding values for weaning and yearling weight were derived and evaluated using a database containing BovineSNP50 genotypes for 7294 animals from 13 breeds in the training set and 2277 animals from seven breeds (Angus, Red Angus, Hereford, Charolais, Gelbvieh, Limousin, and Simmental) in the evaluation set. Six single-breed and four across-breed genomic predictors were trained using pooled data from purebred animals. Molecular breeding values were evaluated using field data, including genotypes for 2227 animals and phenotypic records of animals born in 2008 or later. Accuracies of molecular breeding values were estimated based on the genetic correlation between the molecular breeding value and trait phenotype. Results With one exception, the estimated genetic correlations of within-breed molecular breeding values with trait phenotype were greater than 0.28 when evaluated in the breed used for training. Most estimated genetic correlations for the across-breed trained molecular breeding values were moderate (> 0.30). When molecular breeding values were evaluated in breeds that were not in the training set, estimated genetic correlations clustered around zero. Conclusions Even for closely related breeds, within- or across-breed trained molecular breeding values have limited prediction accuracy for breeds that were not in the training set. For breeds in the training

  20. Genome-wide Association Study of Chicken Plumage Pigmentation.

    PubMed

    Park, Mi Na; Choi, Jin Ae; Lee, Kyung-Tai; Lee, Hyun-Jeong; Choi, Bong-Hwan; Kim, Heebal; Kim, Tae-Hun; Cho, Seoae; Lee, Taeheon

    2013-11-01

    To increase plumage color uniformity and understand the genetic background of Korean chickens, we performed a genome-wide association study of different plumage color in Korean native chickens. We analyzed 60K SNP chips on 279 chickens with GEMMA methods for GWAS and estimated the genetic heritability for plumage color. The estimated heritability suggests that plumage coloration is a polygenic trait. We found new loci associated with feather pigmentation at the genome-wide level and from the results infer that there are additional genetic effect for plumage color. The results will be used for selecting and breeding chicken for plumage color uniformity. PMID:25049737

  1. Genome-wide association studies in pharmacogenomics.

    PubMed

    Daly, Ann K

    2010-04-01

    Genome-wide association (GWA) studies for pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. Until now, only the largest effects have been detected, partly because of the challenges of obtaining large numbers of cases for pharmacogenomic studies. Since 2007, a range of pharmacogenomics GWA studies have been published that have identified several interesting and novel associations between drug responses or reactions and clinically relevant loci, showing the value of this approach. PMID:20300088

  2. Genome-wide association study for semen quality traits in German Warmblood stallions.

    PubMed

    Gottschalk, Maren; Metzger, Julia; Martinsson, Gunilla; Sieme, Harald; Distl, Ottmar

    2016-08-01

    We performed a genome-wide association study for semen quality traits in 139 German Warmblood stallions. Stallions were genotyped using the Illumina equine SNP50 Beadchip. Traits analysed were de-regressed estimated breeding values (EBVs) for gel-free volume, sperm concentration, total number of sperm, progressive motility and the total number of progressively motile sperm. The GWAS revealed 29 SNPs on 12 different chromosomes as genome-wide significantly associated with semen quality traits. For ten genomic regions we could retrieve candidate genes influencing stallion fertility. Among the candidate genes, we could find the genes encoding cysteine-rich secretory proteins (CRISP1, CRISP2 and CRISP3). This was the first GWAS in horses performed for semen quality traits. PMID:27334685

  3. Genome-wide SNP detection, validation, and development of an 8K SNP array for apple

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide...

  4. Genome-Wide Detection of CNVs and Their Association with Meat Tenderness in Nelore Cattle

    PubMed Central

    da Silva, Vinicius Henrique; Regitano, Luciana Correia de Almeida; Geistlinger, Ludwig; Pértille, Fábio; Morosini, Natália Silva; Zimmer, Ralf; Coutinho, Luiz Lehmann

    2016-01-01

    Brazil is one of the largest beef producers and exporters in the world with the Nelore breed representing the vast majority of Brazilian cattle (Bos taurus indicus). Despite the great adaptability of the Nelore breed to tropical climate, meat tenderness (MT) remains to be improved. Several factors including genetic composition can influence MT. In this article, we report a genome-wide analysis of copy number variation (CNV) inferred from Illumina® High Density SNP-chip data for a Nelore population of 723 males. We detected >2,600 CNV regions (CNVRs) representing ≈6.5% of the genome. Comparing our results with previous studies revealed an overlap in ≈1400 CNVRs (>50%). A total of 1,155 CNVRs (43.6%) overlapped 2,750 genes. They were enriched for processes involving guanosine triphosphate (GTP), previously reported to influence skeletal muscle physiology and morphology. Nelore CNVRs also overlapped QTLs for MT reported in other breeds (8.9%, 236 CNVRs) and from a previous study with this population (4.1%, 109 CNVRs). Two CNVRs were also proximal to glutathione metabolism genes that were previously associated with MT. Genome-wide association study of CN state with estimated breeding values derived from meat shear force identified 6 regions, including a region on BTA3 that contains genes of the cAMP and cGMP pathway. Ten CNVRs that overlapped regions associated with MT were successfully validated by qPCR. Our results represent the first comprehensive CNV study in Bos taurus indicus cattle and identify regions in which copy number changes are potentially of importance for the MT phenotype. PMID:27348523

  5. Genome-Wide Detection of CNVs and Their Association with Meat Tenderness in Nelore Cattle.

    PubMed

    Silva, Vinicius Henrique da; Regitano, Luciana Correia de Almeida; Geistlinger, Ludwig; Pértille, Fábio; Giachetto, Poliana Fernanda; Brassaloti, Ricardo Augusto; Morosini, Natália Silva; Zimmer, Ralf; Coutinho, Luiz Lehmann

    2016-01-01

    Brazil is one of the largest beef producers and exporters in the world with the Nelore breed representing the vast majority of Brazilian cattle (Bos taurus indicus). Despite the great adaptability of the Nelore breed to tropical climate, meat tenderness (MT) remains to be improved. Several factors including genetic composition can influence MT. In this article, we report a genome-wide analysis of copy number variation (CNV) inferred from Illumina® High Density SNP-chip data for a Nelore population of 723 males. We detected >2,600 CNV regions (CNVRs) representing ≈6.5% of the genome. Comparing our results with previous studies revealed an overlap in ≈1400 CNVRs (>50%). A total of 1,155 CNVRs (43.6%) overlapped 2,750 genes. They were enriched for processes involving guanosine triphosphate (GTP), previously reported to influence skeletal muscle physiology and morphology. Nelore CNVRs also overlapped QTLs for MT reported in other breeds (8.9%, 236 CNVRs) and from a previous study with this population (4.1%, 109 CNVRs). Two CNVRs were also proximal to glutathione metabolism genes that were previously associated with MT. Genome-wide association study of CN state with estimated breeding values derived from meat shear force identified 6 regions, including a region on BTA3 that contains genes of the cAMP and cGMP pathway. Ten CNVRs that overlapped regions associated with MT were successfully validated by qPCR. Our results represent the first comprehensive CNV study in Bos taurus indicus cattle and identify regions in which copy number changes are potentially of importance for the MT phenotype. PMID:27348523

  6. Genetic diversity in the modern horse illustrated from genome-wide SNP data.

    PubMed

    Petersen, Jessica L; Mickelson, James R; Cothran, E Gus; Andersson, Lisa S; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M; Borges, Alexandre S; Brama, Pieter; da Câmara Machado, Artur; Distl, Ottmar; Felicetti, Michela; Fox-Clipsham, Laura; Graves, Kathryn T; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A; Mikko, Sofia; Orr, Nicholas; Penedo, M Cecilia T; Piercy, Richard J; Raekallio, Marja; Rieder, Stefan; Røed, Knut H; Silvestrelli, Maurizio; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; M Wade, Claire; McCue, Molly E

    2013-01-01

    Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection. PMID:23383025

  7. Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

    PubMed Central

    Petersen, Jessica L.; Mickelson, James R.; Cothran, E. Gus; Andersson, Lisa S.; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M.; Borges, Alexandre S.; Brama, Pieter; da Câmara Machado, Artur; Distl, Ottmar; Felicetti, Michela; Fox-Clipsham, Laura; Graves, Kathryn T.; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A.; Mikko, Sofia; Orr, Nicholas; Penedo, M. Cecilia T; Piercy, Richard J.; Raekallio, Marja; Rieder, Stefan; Røed, Knut H.; Silvestrelli, Maurizio; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; M. Wade, Claire; McCue, Molly E.

    2013-01-01

    Horses were domesticated from the Eurasian steppes 5,000–6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection. PMID:23383025

  8. Genome-wide association analysis identifies loci for left-sided displacement of the abomasum in German Holstein cattle.

    PubMed

    Mömke, S; Sickinger, M; Lichtner, P; Doll, K; Rehage, J; Distl, O

    2013-06-01

    Left-sided displacement of the abomasum (LDA) is one of the most common disorders of the digestive system in many dairy breeds and particularly in Holstein dairy cows. We performed a genome-wide association study for 854 German Holstein cows, including 225 cases and 629 controls. All cows were genotyped using the Illumina Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA). After quality control of genotypes, a total of 36,226 informative single nucleotide polymorphisms (SNP) were left for analysis. We used a mixed linear model approach for a genome-wide association study of LDA. In total, 36 SNP located on 17 bovine (Bos taurus) chromosomes (BTA) showed associations with LDA at nominal -log10P-values >3.0. Two of these SNP, located on BTA11 at 46.70 Mb and BTA20 at 16.67 Mb, showed genome-wide significant associations with LDA at -log10P-values >4.6. Pathway analyses indicated genes involved in calcium metabolism and insulin-dependent diabetes mellitus to be factors in the pathogenesis of LDA in German Holstein cows. PMID:23548285

  9. Efficient estimation of breeding values from dense genomic data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic, phenotypic, and pedigree data can be combined to produce estimated breeding values (EBV) with higher reliability. If coefficient matrix Z includes genotypes for many loci and marker effects (u) are normally distributed with equal variance at each, estimation of u by mixed model equations or...

  10. Genome Wide Analysis of Fertility and Production Traits in Italian Holstein Cattle

    PubMed Central

    Stella, Alessandra; Biffani, Stefano; Negrini, Riccardo; Lazzari, Barbara; Ajmone-Marsan, Paolo; Williams, John L .

    2013-01-01

    A genome wide scan was performed on a total of 2093 Italian Holstein proven bulls genotyped with 50K single nucleotide polymorphisms (SNPs), with the objective of identifying loci associated with fertility related traits and to test their effects on milk production traits. The analysis was carried out using estimated breeding values for the aggregate fertility index and for each trait contributing to the index: angularity, calving interval, non-return rate at 56 days, days to first service, and 305 day first parity lactation. In addition, two production traits not included in the aggregate fertility index were analysed: fat yield and protein yield. Analyses were carried out using all SNPs treated separately, further the most significant marker on BTA14 associated to milk quality located in the DGAT1 region was treated as fixed effect. Genome wide association analysis identified 61 significant SNPs and 75 significant marker-trait associations. Eight additional SNP associations were detected when SNP located near DGAT1 was included as a fixed effect. As there were no obvious common SNPs between the traits analyzed independently in this study, a network analysis was carried out to identify unforeseen relationships that may link production and fertility traits. PMID:24265800

  11. Genome-wide association study on reproductive traits in Jinghai Yellow Chicken.

    PubMed

    Zhang, G X; Fan, Q C; Wang, J Y; Zhang, T; Xue, Q; Shi, H Q

    2015-12-01

    To identify molecular markers and candidate genes associated with reproductive traits, a genome-wide analysis was performed in Jinghai Yellow Chickens to analyze body weight at first oviposition (BWF), age at first oviposition (AFE), weight of the egg at first oviposition (FEW), egg weight at the age of 300 days (EW300), number of eggs produced by 300 days of age (EN300), egg hatchability (HA) and multiple selection index for egg production (MSI). The results showed that seven single nucleotide polymorphisms (SNPs) were associated with reproductive traits (P<1.80E-6, Bonferroni correction). The P-values of the seven SNPs were 5.62E-10, 3.45E-08, 9.76E-07, 8.90E-07, 1.12E-06, 1.42E-07 and 1.48E-07, respectively. These SNPs were located in close proximity to or within the sequence of the five candidate genes, including FAM184B, TTL, RGS1, FBLN5 and PCNX. An additional 46 SNPs that could be associated with reproductive traits were identified (P<3.59E-5, Bonferroni correction). Identification of the candidate genes as well as genome-wide SNPs that may be associated with reproductive traits will greatly advance the understanding of the genetic basis and molecular mechanisms underlying reproductive traits and may have practical significance in breeding programs for the improvements of reproductive traits in the Jinghai Yellow Chicken. PMID:26498507

  12. Accuracy of genomic breeding values in multibreed beef cattle populations derived from deregressed breeding values and phenotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection involves the assessment of genetic merit through prediction equations that allocate genetic variation with dense marker genotypes. It has the potential to provide accurate breeding values for selection candidates at an early age and facilitate selection for expensive or difficult ...

  13. Genome-wide association study of schizophrenia in Ashkenazi Jews.

    PubMed

    Goes, Fernando S; McGrath, John; Avramopoulos, Dimitrios; Wolyniec, Paula; Pirooznia, Mehdi; Ruczinski, Ingo; Nestadt, Gerald; Kenny, Eimear E; Vacic, Vladimir; Peters, Inga; Lencz, Todd; Darvasi, Ariel; Mulle, Jennifer G; Warren, Stephen T; Pulver, Ann E

    2015-12-01

    Schizophrenia is a common, clinically heterogeneous disorder associated with lifelong morbidity and early mortality. Several genetic variants associated with schizophrenia have been identified, but the majority of the heritability remains unknown. In this study, we report on a case-control sample of Ashkenazi Jews (AJ), a founder population that may provide additional insights into genetic etiology of schizophrenia. We performed a genome-wide association analysis (GWAS) of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently, we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640 controls, followed by a meta-analysis and polygenic risk scoring using summary results from Psychiatric GWAS Consortium 2 schizophrenia study. The U.S. AJ sample showed strong evidence of polygenic inheritance (pseudo-R(2) ∼9.7%) and a SNP-heritability estimate of 0.39 (P = 0.00046). We found no genome-wide significant associations in the U.S. sample or in the combined US/Israeli AJ meta-analysis of 1505 cases and 2145 controls. The strongest AJ specific associations (P-values in 10(-6) -10(-7) range) were in the 22q 11.2 deletion region and included the genes TBX1, GLN1, and COMT. Supportive evidence (meta P < 1 × 10(-4) ) was also found for several previously identified genome-wide significant findings, including the HLA region, CNTN4, IMMP2L, and GRIN2A. The meta-analysis of the U.S. sample with the PGC2 results provided initial genome-wide significant evidence for six new loci. Among the novel potential susceptibility genes is PEPD, a gene involved in proline metabolism, which is associated with a Mendelian disorder characterized by developmental delay and cognitive deficits. PMID:26198764

  14. Methods for meta-analysis of genome-wide association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A limitation of many genome-wide association studies (GWA) in animal breeding is that there are many loci with small effect sizes; thus, larger sample sizes (N) are required to guarantee suitable power of detection. For increasing N, results from different GWA can be combined in a meta-analysis (MA-...

  15. Meta-analysis of genome-wide association from genomic prediction models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A limitation of many genome-wide association studies (GWA) in animal breeding is that there are many loci with small effect sizes; thus, larger sample sizes (N) are required to guarantee suitable power of detection. To increase sample size, results from different GWA can be combined in a meta-analys...

  16. Genomic selection & association mapping in rice: effect of trait genetic architecture, training population composition, marker number & statistical model on accuracy of rice genomic selection in elite, tropical rice breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic Selection (GS) is a new breeding method in which genome-wide markers are used to predict the breeding value of individuals in a breeding population. GS has been shown to improve breeding efficiency in dairy cattle and several crop plant species, and here we evaluate for the first time its ef...

  17. Genome-Wide Estimates of Coancestry, Inbreeding and Effective Population Size in the Spanish Holstein Population

    PubMed Central

    Rodríguez-Ramilo, Silvia Teresa; Fernández, Jesús; Toro, Miguel Angel; Hernández, Delfino; Villanueva, Beatriz

    2015-01-01

    Estimates of effective population size in the Holstein cattle breed have usually been low despite the large number of animals that constitute this breed. Effective population size is inversely related to the rates at which coancestry and inbreeding increase and these rates have been high as a consequence of intense and accurate selection. Traditionally, coancestry and inbreeding coefficients have been calculated from pedigree data. However, the development of genome-wide single nucleotide polymorphisms has increased the interest of calculating these coefficients from molecular data in order to improve their accuracy. In this study, genomic estimates of coancestry, inbreeding and effective population size were obtained in the Spanish Holstein population and then compared with pedigree-based estimates. A total of 11,135 animals genotyped with the Illumina BovineSNP50 BeadChip were available for the study. After applying filtering criteria, the final genomic dataset included 36,693 autosomal SNPs and 10,569 animals. Pedigree data from those genotyped animals included 31,203 animals. These individuals represented only the last five generations in order to homogenise the amount of pedigree information across animals. Genomic estimates of coancestry and inbreeding were obtained from identity by descent segments (coancestry) or runs of homozygosity (inbreeding). The results indicate that the percentage of variance of pedigree-based coancestry estimates explained by genomic coancestry estimates was higher than that for inbreeding. Estimates of effective population size obtained from genome-wide and pedigree information were consistent and ranged from about 66 to 79. These low values emphasize the need of controlling the rate of increase of coancestry and inbreeding in Holstein selection programmes. PMID:25880228

  18. Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement.

    PubMed

    Spindel, J E; Begum, H; Akdemir, D; Collard, B; Redoña, E; Jannink, J-L; McCouch, S

    2016-04-01

    To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable to keep pace with demand. Genomic selection (GS) is a new technique that helps accelerate the rate of genetic gain in breeding by using whole-genome data to predict the breeding value of offspring. Here, we describe a new GS model that combines RR-BLUP with markers fit as fixed effects selected from the results of a genome-wide-association study (GWAS) on the RR-BLUP training data. We term this model GS + de novo GWAS. In a breeding population of tropical rice, GS + de novo GWAS outperformed six other models for a variety of traits and in multiple environments. On the basis of these results, we propose an extended, two-part breeding design that can be used to efficiently integrate novel variation into elite breeding populations, thus expanding genetic diversity and enhancing the potential for sustainable productivity gains. PMID:26860200

  19. Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement

    PubMed Central

    Spindel, J E; Begum, H; Akdemir, D; Collard, B; Redoña, E; Jannink, J-L; McCouch, S

    2016-01-01

    To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable to keep pace with demand. Genomic selection (GS) is a new technique that helps accelerate the rate of genetic gain in breeding by using whole-genome data to predict the breeding value of offspring. Here, we describe a new GS model that combines RR-BLUP with markers fit as fixed effects selected from the results of a genome-wide-association study (GWAS) on the RR-BLUP training data. We term this model GS + de novo GWAS. In a breeding population of tropical rice, GS + de novo GWAS outperformed six other models for a variety of traits and in multiple environments. On the basis of these results, we propose an extended, two-part breeding design that can be used to efficiently integrate novel variation into elite breeding populations, thus expanding genetic diversity and enhancing the potential for sustainable productivity gains. PMID:26860200

  20. Progress of genome wide association study in domestic animals

    PubMed Central

    2012-01-01

    Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described. PMID:22958308

  1. Genome-Wide Association Studies: A Primer

    PubMed Central

    Corvin, Aiden; Craddock, Nick; Sullivan, Patrick F.

    2014-01-01

    There have been nearly 400genome-wide association studies published since 2005. The GWAS approach has been exceptionally successful in identifying common genetic variants that predispose to a variety of complex human diseases and biochemical and anthropometric traits. Although this approach is relatively new, there are many excellent reviews of different aspects of the GWAS method. Here, we provide a primer, an annotated overview of the GWAS method with particular reference to psychiatric genetics. We dissect the GWAS methodology into its components and provide a brief description with citations and links to reviews that cover the topic in detail. PMID:19895722

  2. Genome-wide association studies in neurology

    PubMed Central

    Tan, Meng-Shan; Jiang, Teng

    2014-01-01

    Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWAS in common neurological diseases, including Stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, migraine, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, restless legs syndrome, intracranial aneurysm, human prion diseases and moyamoya disease. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of potential therapeutic agents. PMID:25568877

  3. Multiple trait genomic selection methods increase genetic value prediction accuracy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection predicts genetic values with genome-wide markers. It is rapidly emerging in plant breeding and is widely implemented in animal breeding. Genetic correlations between quantitative traits are pervasive in many breeding programs. These correlations indicate that measurements of one tr...

  4. Genome-wide identification of enhancer elements.

    PubMed

    Tulin, Sarah; Barsi, Julius C; Bocconcelli, Carlo; Smith, Joel

    2016-01-01

    We present a prospective genome-wide regulatory element database for the sea urchin embryo and the modified chromosome capture-related methodology used to create it. The method we developed is termed GRIP-seq for genome-wide regulatory element immunoprecipitation and combines features of chromosome conformation capture, chromatin immunoprecipitation, and paired-end next-generation sequencing with molecular steps that enrich for active cis-regulatory elements associated with basal transcriptional machinery. The first GRIP-seq database, available to the community, comes from S. purpuratus 24 hpf embryos and takes advantage of the extremely well-characterized cis-regulatory elements in this system for validation. In addition, using the GRIP-seq database, we identify and experimentally validate a novel, intronic cis-regulatory element at the onecut locus. We find GRIP-seq signal sensitively identifies active cis-regulatory elements with a high signal-to-noise ratio for both distal and intronic elements. This promising GRIP-seq protocol has the potential to address a rate-limiting step in resolving comprehensive, predictive network models in all systems. PMID:27389984

  5. Effect of breed and body weight on echocardiographic values in four breeds of dogs of differing somatotype.

    PubMed

    Morrison, S A; Moise, N S; Scarlett, J; Mohammed, H; Yeager, A E

    1992-01-01

    Eighty normal dogs of four morphologically disparate breeds (Pembroke Welsh Corgi, Miniature Poodle, Afghan Hound, Golden Retriever) (twenty of each breed), were studied by echocardiography to determine the importance of breed and weight in establishing normal echocardiographic reference ranges. Echocardiographic measurements included left-ventricular chamber dimension at systole and end-diastole, right-ventricular chamber dimension at end-diastole, interventricular septal thickness at systole and end-diastole, left-ventricular free wall thickness at systole and end-diastole, E-point septal separation, aortic root dimension at end-diastole, left atrial dimension, and fractional shortening. Analyses of covariance indicated that for all measurements except right-ventricular chamber dimension, the means were significantly different among breeds, after the differences in weight were taken into account. Echocardiographic measurements are variable even within the same breed. Breed must be considered in establishing echocardiographic measurement reference ranges. Echocardiographic values for each breed are presented. PMID:1522552

  6. Genome-wide association study of obsessive-compulsive disorder.

    PubMed

    Stewart, S E; Yu, D; Scharf, J M; Neale, B M; Fagerness, J A; Mathews, C A; Arnold, P D; Evans, P D; Gamazon, E R; Davis, L K; Osiecki, L; McGrath, L; Haddad, S; Crane, J; Hezel, D; Illman, C; Mayerfeld, C; Konkashbaev, A; Liu, C; Pluzhnikov, A; Tikhomirov, A; Edlund, C K; Rauch, S L; Moessner, R; Falkai, P; Maier, W; Ruhrmann, S; Grabe, H-J; Lennertz, L; Wagner, M; Bellodi, L; Cavallini, M C; Richter, M A; Cook, E H; Kennedy, J L; Rosenberg, D; Stein, D J; Hemmings, S M J; Lochner, C; Azzam, A; Chavira, D A; Fournier, E; Garrido, H; Sheppard, B; Umaña, P; Murphy, D L; Wendland, J R; Veenstra-VanderWeele, J; Denys, D; Blom, R; Deforce, D; Van Nieuwerburgh, F; Westenberg, H G M; Walitza, S; Egberts, K; Renner, T; Miguel, E C; Cappi, C; Hounie, A G; Conceição do Rosário, M; Sampaio, A S; Vallada, H; Nicolini, H; Lanzagorta, N; Camarena, B; Delorme, R; Leboyer, M; Pato, C N; Pato, M T; Voyiaziakis, E; Heutink, P; Cath, D C; Posthuma, D; Smit, J H; Samuels, J; Bienvenu, O J; Cullen, B; Fyer, A J; Grados, M A; Greenberg, B D; McCracken, J T; Riddle, M A; Wang, Y; Coric, V; Leckman, J F; Bloch, M; Pittenger, C; Eapen, V; Black, D W; Ophoff, R A; Strengman, E; Cusi, D; Turiel, M; Frau, F; Macciardi, F; Gibbs, J R; Cookson, M R; Singleton, A; Hardy, J; Crenshaw, A T; Parkin, M A; Mirel, D B; Conti, D V; Purcell, S; Nestadt, G; Hanna, G L; Jenike, M A; Knowles, J A; Cox, N; Pauls, D L

    2013-07-01

    Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

  7. Genome-Wide Association Study of Metabolic Syndrome in Koreans

    PubMed Central

    Jeong, Seok Won; Chung, Myungguen; Park, Soo-Jung; Cho, Seong Beom

    2014-01-01

    Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (<5 × 10-8), 8 SNPs with genome-wide suggestive p-values (5 × 10-8 ≤ p < 1 × 10-5), and 2 SNPs of more functional variants with borderline p-values (5 × 10-5 ≤ p < 1 × 10-4). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies. PMID:25705157

  8. A genome-wide DNA methylation study in colorectal carcinoma

    PubMed Central

    2011-01-01

    Background We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC). Methods We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center. Results We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application. Conclusion Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application. PMID:21699707

  9. Genome-Wide Association Study of Parity in Bangladeshi Women

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L.; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G.; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10-7 and number of pregnancies at P <10-6. This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10-6. The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10-5 for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  10. Genome-wide association study of parity in Bangladeshi women.

    PubMed

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10(-7) and number of pregnancies at P <10(-6). This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10(-6). The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10(-5) for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  11. GWIDD: Genome-wide protein docking database

    PubMed Central

    Kundrotas, Petras J.; Zhu, Zhengwei; Vakser, Ilya A.

    2010-01-01

    Structural information on interacting proteins is important for understanding life processes at the molecular level. Genome-wide docking database is an integrated resource for structural studies of protein–protein interactions on the genome scale, which combines the available experimental data with models obtained by docking techniques. Current database version (August 2009) contains 25 559 experimental and modeled 3D structures for 771 organisms spanned over the entire universe of life from viruses to humans. Data are organized in a relational database with user-friendly search interface allowing exploration of the database content by a number of parameters. Search results can be interactively previewed and downloaded as PDB-formatted files, along with the information relevant to the specified interactions. The resource is freely available at http://gwidd.bioinformatics.ku.edu. PMID:19900970

  12. Genome-Wide Association Studies of Cancer

    PubMed Central

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  13. Genome-wide Membrane Protein Structure Prediction

    PubMed Central

    Piccoli, Stefano; Suku, Eda; Garonzi, Marianna; Giorgetti, Alejandro

    2013-01-01

    Transmembrane proteins allow cells to extensively communicate with the external world in a very accurate and specific way. They form principal nodes in several signaling pathways and attract large interest in therapeutic intervention, as the majority pharmaceutical compounds target membrane proteins. Thus, according to the current genome annotation methods, a detailed structural/functional characterization at the protein level of each of the elements codified in the genome is also required. The extreme difficulty in obtaining high-resolution three-dimensional structures, calls for computational approaches. Here we review to which extent the efforts made in the last few years, combining the structural characterization of membrane proteins with protein bioinformatics techniques, could help describing membrane proteins at a genome-wide scale. In particular we analyze the use of comparative modeling techniques as a way of overcoming the lack of high-resolution three-dimensional structures in the human membrane proteome. PMID:24403851

  14. Assessing Predictive Properties of Genome-Wide Selection in Soybeans

    PubMed Central

    Xavier, Alencar; Muir, William M.; Rainey, Katy Martin

    2016-01-01

    Many economically important traits in plant breeding have low heritability or are difficult to measure. For these traits, genomic selection has attractive features and may boost genetic gains. Our goal was to evaluate alternative scenarios to implement genomic selection for yield components in soybean (Glycine max L. merr). We used a nested association panel with cross validation to evaluate the impacts of training population size, genotyping density, and prediction model on the accuracy of genomic prediction. Our results indicate that training population size was the factor most relevant to improvement in genome-wide prediction, with greatest improvement observed in training sets up to 2000 individuals. We discuss assumptions that influence the choice of the prediction model. Although alternative models had minor impacts on prediction accuracy, the most robust prediction model was the combination of reproducing kernel Hilbert space regression and BayesB. Higher genotyping density marginally improved accuracy. Our study finds that breeding programs seeking efficient genomic selection in soybeans would best allocate resources by investing in a representative training set. PMID:27317786

  15. Assessing Predictive Properties of Genome-Wide Selection in Soybeans.

    PubMed

    Xavier, Alencar; Muir, William M; Rainey, Katy Martin

    2016-01-01

    Many economically important traits in plant breeding have low heritability or are difficult to measure. For these traits, genomic selection has attractive features and may boost genetic gains. Our goal was to evaluate alternative scenarios to implement genomic selection for yield components in soybean (Glycine max L. merr). We used a nested association panel with cross validation to evaluate the impacts of training population size, genotyping density, and prediction model on the accuracy of genomic prediction. Our results indicate that training population size was the factor most relevant to improvement in genome-wide prediction, with greatest improvement observed in training sets up to 2000 individuals. We discuss assumptions that influence the choice of the prediction model. Although alternative models had minor impacts on prediction accuracy, the most robust prediction model was the combination of reproducing kernel Hilbert space regression and BayesB. Higher genotyping density marginally improved accuracy. Our study finds that breeding programs seeking efficient genomic selection in soybeans would best allocate resources by investing in a representative training set. PMID:27317786

  16. Genome-Wide Association Studies for Comb Traits in Chickens.

    PubMed

    Shen, Manman; Qu, Liang; Ma, Meng; Dou, Taocun; Lu, Jian; Guo, Jun; Hu, Yuping; Yi, Guoqiang; Yuan, Jingwei; Sun, Congjiao; Wang, Kehua; Yang, Ning

    2016-01-01

    The comb, as a secondary sexual character, is an important trait in chicken. Indicators of comb length (CL), comb height (CH), and comb weight (CW) are often selected in production. DNA-based marker-assisted selection could help chicken breeders to accelerate genetic improvement for comb or related economic characters by early selection. Although a number of quantitative trait loci (QTL) and candidate genes have been identified with advances in molecular genetics, candidate genes underlying comb traits are limited. The aim of the study was to use genome-wide association (GWA) studies by 600 K Affymetrix chicken SNP arrays to detect genes that are related to comb, using an F2 resource population. For all comb characters, comb exhibited high SNP-based heritability estimates (0.61-0.69). Chromosome 1 explained 20.80% genetic variance, while chromosome 4 explained 6.89%. Independent univariate genome-wide screens for each character identified 127, 197, and 268 novel significant SNPs with CL, CH, and CW, respectively. Three candidate genes, VPS36, AR, and WNT11B, were determined to have a plausible function in all comb characters. These genes are important to the initiation of follicle development, gonadal growth, and dermal development, respectively. The current study provides the first GWA analysis for comb traits. Identification of the genetic basis as well as promising candidate genes will help us understand the underlying genetic architecture of comb development and has practical significance in breeding programs for the selection of comb as an index for sexual maturity or reproduction. PMID:27427764

  17. Genome-Wide Association Studies for Comb Traits in Chickens

    PubMed Central

    Ma, Meng; Dou, Taocun; Lu, Jian; Guo, Jun; Hu, Yuping; Yi, Guoqiang; Yuan, Jingwei; Sun, Congjiao; Wang, Kehua; Yang, Ning

    2016-01-01

    The comb, as a secondary sexual character, is an important trait in chicken. Indicators of comb length (CL), comb height (CH), and comb weight (CW) are often selected in production. DNA-based marker-assisted selection could help chicken breeders to accelerate genetic improvement for comb or related economic characters by early selection. Although a number of quantitative trait loci (QTL) and candidate genes have been identified with advances in molecular genetics, candidate genes underlying comb traits are limited. The aim of the study was to use genome-wide association (GWA) studies by 600 K Affymetrix chicken SNP arrays to detect genes that are related to comb, using an F2 resource population. For all comb characters, comb exhibited high SNP-based heritability estimates (0.61–0.69). Chromosome 1 explained 20.80% genetic variance, while chromosome 4 explained 6.89%. Independent univariate genome-wide screens for each character identified 127, 197, and 268 novel significant SNPs with CL, CH, and CW, respectively. Three candidate genes, VPS36, AR, and WNT11B, were determined to have a plausible function in all comb characters. These genes are important to the initiation of follicle development, gonadal growth, and dermal development, respectively. The current study provides the first GWA analysis for comb traits. Identification of the genetic basis as well as promising candidate genes will help us understand the underlying genetic architecture of comb development and has practical significance in breeding programs for the selection of comb as an index for sexual maturity or reproduction. PMID:27427764

  18. Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

    PubMed Central

    Tonomura, Noriko; Elvers, Ingegerd; Thomas, Rachael; Megquier, Kate; Turner-Maier, Jason; Howald, Cedric; Sarver, Aaron L.; Swofford, Ross; Frantz, Aric M.; Ito, Daisuke; Mauceli, Evan; Arendt, Maja; Noh, Hyun Ji; Koltookian, Michele; Biagi, Tara; Fryc, Sarah; Williams, Christina; Avery, Anne C.; Kim, Jong-Hyuk; Barber, Lisa; Burgess, Kristine; Lander, Eric S.; Karlsson, Elinor K.; Azuma, Chieko

    2015-01-01

    Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers. PMID:25642983

  19. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

    PubMed

    Tonomura, Noriko; Elvers, Ingegerd; Thomas, Rachael; Megquier, Kate; Turner-Maier, Jason; Howald, Cedric; Sarver, Aaron L; Swofford, Ross; Frantz, Aric M; Ito, Daisuke; Mauceli, Evan; Arendt, Maja; Noh, Hyun Ji; Koltookian, Michele; Biagi, Tara; Fryc, Sarah; Williams, Christina; Avery, Anne C; Kim, Jong-Hyuk; Barber, Lisa; Burgess, Kristine; Lander, Eric S; Karlsson, Elinor K; Azuma, Chieko; Modiano, Jaime F; Breen, Matthew; Lindblad-Toh, Kerstin

    2015-02-01

    Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers. PMID:25642983

  20. Genomic selection accuracy using multi-family prediction models in a wheat breeding program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection (GS) uses genome-wide molecular marker data to predict the genetic value of selection candidates in breeding programs. In plant breeding, the ability to produce large numbers of progeny per cross allows GS to be conducted within each family. However, this approach requires phenotyp...

  1. Genome-Wide Association Study for Indicator Traits of Sexual Precocity in Nellore Cattle

    PubMed Central

    Irano, Natalia; de Camargo, Gregório Miguel Ferreira; Costa, Raphael Bermal; Terakado, Ana Paula Nascimento; Magalhães, Ana Fabrícia Braga; Silva, Rafael Medeiros de Oliveira; Dias, Marina Mortati; Bignardi, Annaiza Braga; Baldi, Fernando; Carvalheiro, Roberto; de Oliveira, Henrique Nunes; de Albuquerque, Lucia Galvão

    2016-01-01

    The objective of this study was to perform a genome-wide association study (GWAS) to detect chromosome regions associated with indicator traits of sexual precocity in Nellore cattle. Data from Nellore animals belonging to farms which participate in the DeltaGen® and Paint® animal breeding programs, were used. The traits used in this study were the occurrence of early pregnancy (EP) and scrotal circumference (SC). Data from 72,675 females and 83,911 males with phenotypes were used; of these, 1,770 females and 1,680 males were genotyped. The SNP effects were estimated with a single-step procedure (WssGBLUP) and the observed phenotypes were used as dependent variables. All animals with available genotypes and phenotypes, in addition to those with only phenotypic information, were used. A single-trait animal model was applied to predict breeding values and the solutions of SNP effects were obtained from these breeding values. The results of GWAS are reported as the proportion of variance explained by windows with 150 adjacent SNPs. The 10 windows that explained the highest proportion of variance were identified. The results of this study indicate the polygenic nature of EP and SC, demonstrating that the indicator traits of sexual precocity studied here are probably controlled by many genes, including some of moderate effect. The 10 windows with large effects obtained for EP are located on chromosomes 5, 6, 7, 14, 18, 21 and 27, and together explained 7.91% of the total genetic variance. For SC, these windows are located on chromosomes 4, 8, 11, 13, 14, 19, 22 and 23, explaining 6.78% of total variance. GWAS permitted to identify chromosome regions associated with EP and SC. The identification of these regions contributes to a better understanding and evaluation of these traits, and permits to indicate candidate genes for future investigation of causal mutations. PMID:27494397

  2. Genome-Wide Association Study for Indicator Traits of Sexual Precocity in Nellore Cattle.

    PubMed

    Irano, Natalia; de Camargo, Gregório Miguel Ferreira; Costa, Raphael Bermal; Terakado, Ana Paula Nascimento; Magalhães, Ana Fabrícia Braga; Silva, Rafael Medeiros de Oliveira; Dias, Marina Mortati; Bignardi, Annaiza Braga; Baldi, Fernando; Carvalheiro, Roberto; de Oliveira, Henrique Nunes; de Albuquerque, Lucia Galvão

    2016-01-01

    The objective of this study was to perform a genome-wide association study (GWAS) to detect chromosome regions associated with indicator traits of sexual precocity in Nellore cattle. Data from Nellore animals belonging to farms which participate in the DeltaGen® and Paint® animal breeding programs, were used. The traits used in this study were the occurrence of early pregnancy (EP) and scrotal circumference (SC). Data from 72,675 females and 83,911 males with phenotypes were used; of these, 1,770 females and 1,680 males were genotyped. The SNP effects were estimated with a single-step procedure (WssGBLUP) and the observed phenotypes were used as dependent variables. All animals with available genotypes and phenotypes, in addition to those with only phenotypic information, were used. A single-trait animal model was applied to predict breeding values and the solutions of SNP effects were obtained from these breeding values. The results of GWAS are reported as the proportion of variance explained by windows with 150 adjacent SNPs. The 10 windows that explained the highest proportion of variance were identified. The results of this study indicate the polygenic nature of EP and SC, demonstrating that the indicator traits of sexual precocity studied here are probably controlled by many genes, including some of moderate effect. The 10 windows with large effects obtained for EP are located on chromosomes 5, 6, 7, 14, 18, 21 and 27, and together explained 7.91% of the total genetic variance. For SC, these windows are located on chromosomes 4, 8, 11, 13, 14, 19, 22 and 23, explaining 6.78% of total variance. GWAS permitted to identify chromosome regions associated with EP and SC. The identification of these regions contributes to a better understanding and evaluation of these traits, and permits to indicate candidate genes for future investigation of causal mutations. PMID:27494397

  3. Breeding value estimation in the Hungarian Sport Horse population.

    PubMed

    Posta, János; Komlósi, István; Mihók, Sándor

    2009-07-01

    The aims of this study were to estimate phenotypic and genetic parameters for a range of traits in Hungarian Sport Horses, and to compare several methods of estimating breeding value (BV) in this breed. The analyses were based on the Hungarian Sport Horse Studbook, results of self-performance tests (SPTs) and show-jumping competition results. An SPT comprises subjective judgement of conformation traits, movement analysis traits and free-jumping performance, assessed via ordinal scores. Genetic parameters of SPTs were estimated with an animal model. Different measurements of the competition performance were compared using the same repeatability model. Estimates of BV for sport were made with random regression models using a first-order Legendre polynomial. Heritability was found to increase and permanent environmental variance to decrease continuously with age. BVs can be estimated at different ages and from these a composite BV index can be computed. It is possible to weight BVs for the specific age of a horse. PMID:19375365

  4. Comparison of molecular breeding values based on within- and across-breed training in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Although the efficacy of genomic predictors based on within-breed training looks promising, it is necessary to develop and evaluate across-breed predictors for the technology to be fully applied in the beef industry. The efficacies of genomic predictors trained in one breed and utilized ...

  5. Genome-wide gene-based association study.

    PubMed

    Yang, Hsin-Chou; Liang, Yu-Jen; Chung, Chia-Min; Chen, Jia-Wei; Pan, Wen-Harn

    2009-01-01

    Genome-wide association studies, which analyzes hundreds of thousands of single-nucleotide polymorphisms to identify disease susceptibility genes, are challenging because the work involves intensive computation and complex modeling. We propose a two-stage genome-wide association scanning procedure, consisting of a single-locus association scan for the first stage and a gene-based association scan for the second stage. Marginal effects of single-nucleotide polymorphisms are examined by using the exact Armitage trend test or logistic regression, and gene effects are examined by using a p-value combination method. Compared with some existing single-locus and multilocus methods, the proposed method has the following merits: 1) convenient for definition of biologically meaningful regions, 2) powerful for detection of minor-effect genes, 3) helpful for alleviation of a multiple-testing problem, and 4) convenient for result interpretation. The method was applied to study Genetic Analysis Workshop 16 Problem 1 rheumatoid arthritis data, and strong association signals were found. The results show that the human major histocompatibility complex region is the most important genomic region associated with rheumatoid arthritis. Moreover, previously reported genes including PTPN22, C5, and IL2RB were confirmed; novel genes including HLA-DRA, BTNL2, C6orf10, NOTCH4, TAP2, and TNXB were identified by our analysis. PMID:20018002

  6. A Pooled Genome-Wide Association Study of Asperger Syndrome

    PubMed Central

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E.; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision. PMID:26176695

  7. Genome-wide analysis correlates Ayurveda Prakriti

    PubMed Central

    Govindaraj, Periyasamy; Nizamuddin, Sheikh; Sharath, Anugula; Jyothi, Vuskamalla; Rotti, Harish; Raval, Ritu; Nayak, Jayakrishna; Bhat, Balakrishna K.; Prasanna, B. V.; Shintre, Pooja; Sule, Mayura; Joshi, Kalpana S.; Dedge, Amrish P.; Bharadwaj, Ramachandra; Gangadharan, G. G.; Nair, Sreekumaran; Gopinath, Puthiya M.; Patwardhan, Bhushan; Kondaiah, Paturu; Satyamoorthy, Kapaettu; Valiathan, Marthanda Varma Sankaran; Thangaraj, Kumarasamy

    2015-01-01

    The practice of Ayurveda, the traditional medicine of India, is based on the concept of three major constitutional types (Vata, Pitta and Kapha) defined as “Prakriti”. To the best of our knowledge, no study has convincingly correlated genomic variations with the classification of Prakriti. In the present study, we performed genome-wide SNP (single nucleotide polymorphism) analysis (Affymetrix, 6.0) of 262 well-classified male individuals (after screening 3416 subjects) belonging to three Prakritis. We found 52 SNPs (p ≤ 1 × 10−5) were significantly different between Prakritis, without any confounding effect of stratification, after 106 permutations. Principal component analysis (PCA) of these SNPs classified 262 individuals into their respective groups (Vata, Pitta and Kapha) irrespective of their ancestry, which represent its power in categorization. We further validated our finding with 297 Indian population samples with known ancestry. Subsequently, we found that PGM1 correlates with phenotype of Pitta as described in the ancient text of Caraka Samhita, suggesting that the phenotypic classification of India’s traditional medicine has a genetic basis; and its Prakriti-based practice in vogue for many centuries resonates with personalized medicine. PMID:26511157

  8. Genome Wide Methylome Alterations in Lung Cancer.

    PubMed

    Mullapudi, Nandita; Ye, Bin; Suzuki, Masako; Fazzari, Melissa; Han, Weiguo; Shi, Miao K; Marquardt, Gaby; Lin, Juan; Wang, Tao; Keller, Steven; Zhu, Changcheng; Locker, Joseph D; Spivack, Simon D

    2015-01-01

    Aberrant cytosine 5-methylation underlies many deregulated elements of cancer. Among paired non-small cell lung cancers (NSCLC), we sought to profile DNA 5-methyl-cytosine features which may underlie genome-wide deregulation. In one of the more dense interrogations of the methylome, we sampled 1.2 million CpG sites from twenty-four NSCLC tumor (T)-non-tumor (NT) pairs using a methylation-sensitive restriction enzyme- based HELP-microarray assay. We found 225,350 differentially methylated (DM) sites in adenocarcinomas versus adjacent non-tumor tissue that vary in frequency across genomic compartment, particularly notable in gene bodies (GB; p<2.2E-16). Further, when DM was coupled to differential transcriptome (DE) in the same samples, 37,056 differential loci in adenocarcinoma emerged. Approximately 90% of the DM-DE relationships were non-canonical; for example, promoter DM associated with DE in the same direction. Of the canonical changes noted, promoter (PR) DM loci with reciprocal changes in expression in adenocarcinomas included HBEGF, AGER, PTPRM, DPT, CST1, MELK; DM GB loci with concordant changes in expression included FOXM1, FERMT1, SLC7A5, and FAP genes. IPA analyses showed adenocarcinoma-specific promoter DMxDE overlay identified familiar lung cancer nodes [tP53, Akt] as well as less familiar nodes [HBEGF, NQO1, GRK5, VWF, HPGD, CDH5, CTNNAL1, PTPN13, DACH1, SMAD6, LAMA3, AR]. The unique findings from this study include the discovery of numerous candidate The unique findings from this study include the discovery of numerous candidate methylation sites in both PR and GB regions not previously identified in NSCLC, and many non-canonical relationships to gene expression. These DNA methylation features could potentially be developed as risk or diagnostic biomarkers, or as candidate targets for newer methylation locus-targeted preventive or therapeutic agents. PMID:26683690

  9. Genome Wide Methylome Alterations in Lung Cancer

    PubMed Central

    Suzuki, Masako; Fazzari, Melissa; Han, Weiguo; Shi, Miao K.; Marquardt, Gaby; Lin, Juan; Wang, Tao; Keller, Steven; Zhu, Changcheng; Locker, Joseph D.; Spivack, Simon D.

    2015-01-01

    Aberrant cytosine 5-methylation underlies many deregulated elements of cancer. Among paired non-small cell lung cancers (NSCLC), we sought to profile DNA 5-methyl-cytosine features which may underlie genome-wide deregulation. In one of the more dense interrogations of the methylome, we sampled 1.2 million CpG sites from twenty-four NSCLC tumor (T)–non-tumor (NT) pairs using a methylation-sensitive restriction enzyme- based HELP-microarray assay. We found 225,350 differentially methylated (DM) sites in adenocarcinomas versus adjacent non-tumor tissue that vary in frequency across genomic compartment, particularly notable in gene bodies (GB; p<2.2E-16). Further, when DM was coupled to differential transcriptome (DE) in the same samples, 37,056 differential loci in adenocarcinoma emerged. Approximately 90% of the DM-DE relationships were non-canonical; for example, promoter DM associated with DE in the same direction. Of the canonical changes noted, promoter (PR) DM loci with reciprocal changes in expression in adenocarcinomas included HBEGF, AGER, PTPRM, DPT, CST1, MELK; DM GB loci with concordant changes in expression included FOXM1, FERMT1, SLC7A5, and FAP genes. IPA analyses showed adenocarcinoma-specific promoter DMxDE overlay identified familiar lung cancer nodes [tP53, Akt] as well as less familiar nodes [HBEGF, NQO1, GRK5, VWF, HPGD, CDH5, CTNNAL1, PTPN13, DACH1, SMAD6, LAMA3, AR]. The unique findings from this study include the discovery of numerous candidate The unique findings from this study include the discovery of numerous candidate methylation sites in both PR and GB regions not previously identified in NSCLC, and many non-canonical relationships to gene expression. These DNA methylation features could potentially be developed as risk or diagnostic biomarkers, or as candidate targets for newer methylation locus-targeted preventive or therapeutic agents. PMID:26683690

  10. Genome-wide methylation profiling of schizophrenia.

    PubMed

    Rukova, B; Staneva, R; Hadjidekova, S; Stamenov, G; Milanova; Toncheva, D

    2014-12-01

    Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220 schizophrenia patients; 220 age-matched healthy controls; 110 female schizophrenia patients; 110 age-matched healthy females; 110 male schizophrenia patients; 110 age-matched healthy males. We also investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile between schizophrenia and control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2, FNDC4 and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles between schizophrenia patients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role in schizophrenia pathogenesis. PMID:25937794

  11. Genome-Wide Methylation Profiling of Schizophrenia

    PubMed Central

    Rukova, B; Staneva, R; Hadjidekova, S; Stamenov, G; Milanova; Toncheva, D

    2014-01-01

    Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220 schizophrenia patients; 220 age-matched healthy controls; 110 female schizophrenia patients; 110 age-matched healthy females; 110 male schizophrenia patients; 110 age-matched healthy males. We also investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile between schizophrenia and control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2, FNDC4 and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles between schizophrenia patients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role in schizophrenia pathogenesis. PMID:25937794

  12. Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm

    PubMed Central

    2011-01-01

    Background Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i) explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii) investigate the genome-wide distribution of genetic diversity, and (iii) assess the extent and genome-wide distribution of linkage disequilibrium (LD) in elite sugar beet germplasm. Results A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that r2 >0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping. Conclusions We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of genome-wide association

  13. Integration of DNA marker information into breeding value predictions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calves from seven breeds including 20 herds were genotyped with a reduced DNA marker panel for weaning weight. The marker panel used was derived using USMARC Cycle VII animals. The results from the current study suggest marker effects are not robust across breeds and that methodology exists to integ...

  14. Chronic Periodontitis Genome-wide Association Studies

    PubMed Central

    Rhodin, K.; Divaris, K.; North, K.E.; Barros, S.P.; Moss, K.; Beck, J.D.; Offenbacher, S.

    2014-01-01

    Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer rich data sources for the investigation of candidate genes, functional elements, and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen colonization (n = 1,020) from a cohort of adult Americans of European descent participating in the Atherosclerosis Risk in Communities study and employed a MAGENTA approach (i.e., meta-analysis gene set enrichment of variant associations) to obtain gene-centric and gene set association results corrected for gene size, number of single-nucleotide polymorphisms, and local linkage disequilibrium characteristics based on the human genome build 18 (National Center for Biotechnology Information build 36). We used the Gene Ontology, Ingenuity, KEGG, Panther, Reactome, and Biocarta databases for gene set enrichment analyses. Six genes showed evidence of statistically significant association: 4 with severe CP (NIN, p = 1.6 × 10−7; ABHD12B, p = 3.6 × 10−7; WHAMM, p = 1.7 × 10−6; AP3B2, p = 2.2 × 10−6) and 2 with high periodontal pathogen colonization (red complex–KCNK1, p = 3.4 × 10−7; Porphyromonas gingivalis–DAB2IP, p = 1.0 × 10−6). Top-ranked genes for moderate CP were HGD (p = 1.4 × 10−5), ZNF675 (p = 1.5 × 10−5), TNFRSF10C (p = 2.0 × 10−5), and EMR1 (p = 2.0 × 10−5). Loci containing NIN, EMR1, KCNK1, and DAB2IP had showed suggestive evidence of association in the earlier single-nucleotide polymorphism–based analyses, whereas WHAMM and AP2B2 emerged as novel candidates. The top gene sets included severe CP (“endoplasmic reticulum membrane,” “cytochrome P450,” “microsome,” and “oxidation reduction”) and moderate CP (“regulation of gene expression,” “zinc ion binding,” “BMP signaling pathway,” and “ruffle”). Gene-centric analyses offer a promising avenue for efficient interrogation of large-scale GWAS data. These results highlight genes in previously identified loci and

  15. Incorporating molecular breeding values with variable call rates into genetic evaluations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A partial genotype for an animal can result from panels with low call rates used to calculate a molecular breeding value. A molecular breeding value can still be calculated using a partial genotype by replacing the missing marker covariates with their mean value. This approach is expected to chang...

  16. Assessing genomic selection prediction accuracy in a dynamic barley breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection is a method to improve quantitative traits in crops and livestock by estimating breeding values of selection candidates using phenotype and genome-wide marker data sets. Prediction accuracy has been evaluated through simulation and cross-validation, however validation based on prog...

  17. Systems-Level Analysis of Genome-Wide Association Data

    PubMed Central

    Farber, Charles R.

    2013-01-01

    Genome-wide association studies (GWAS) have emerged as the method of choice for identifying common variants affecting complex disease. In a GWAS, particular attention is placed, for obvious reasons, on single-nucleotide polymorphisms (SNPs) that exceed stringent genome-wide significance thresholds. However, it is expected that many SNPs with only nominal evidence of association (e.g., P < 0.05) truly influence disease. Efforts to extract additional biological information from entire GWAS datasets have primarily focused on pathway-enrichment analyses. However, these methods suffer from a number of limitations and typically fail to lead to testable hypotheses. To evaluate alternative approaches, we performed a systems-level analysis of GWAS data using weighted gene coexpression network analysis. A weighted gene coexpression network was generated for 1918 genes harboring SNPs that displayed nominal evidence of association (P ≤ 0.05) from a GWAS of bone mineral density (BMD) using microarray data on circulating monocytes isolated from individuals with extremely low or high BMD. Thirteen distinct gene modules were identified, each comprising coexpressed and highly interconnected GWAS genes. Through the characterization of module content and topology, we illustrate how network analysis can be used to discover disease-associated subnetworks and characterize novel interactions for genes with a known role in the regulation of BMD. In addition, we provide evidence that network metrics can be used as a prioritizing tool when selecting genes and SNPs for replication studies. Our results highlight the advantages of using systems-level strategies to add value to and inform GWAS. PMID:23316444

  18. Beef cattle body temperature during climatic stress: a genome-wide association study

    NASA Astrophysics Data System (ADS)

    Howard, Jeremy T.; Kachman, Stephen D.; Snelling, Warren M.; Pollak, E. John; Ciobanu, Daniel C.; Kuehn, Larry A.; Spangler, Matthew L.

    2014-09-01

    Cattle are reared in diverse environments and collecting phenotypic body temperature (BT) measurements to characterize BT variation across diverse environments is difficult and expensive. To better understand the genetic basis of BT regulation, a genome-wide association study was conducted utilizing crossbred steers and heifers totaling 239 animals of unknown pedigree and breed fraction. During predicted extreme heat and cold stress events, hourly tympanic and vaginal BT devices were placed in steers and heifers, respectively. Individuals were genotyped with the BovineSNP50K_v2 assay and data analyzed using Bayesian models for area under the curve (AUC), a measure of BT over time, using hourly BT observations summed across 5-days (AUC summer 5-day (AUCS5D) and AUC winter 5-day (AUCW5D)). Posterior heritability estimates were moderate to high and were estimated to be 0.68 and 0.21 for AUCS5D and AUCW5D, respectively. Moderately positive correlations between direct genomic values for AUCS5D and AUCW5D (0.40) were found, although a small percentage of the top 5 % 1-Mb windows were in common. Different sets of genes were associated with BT during winter and summer, thus simultaneous selection for animals tolerant to both heat and cold appears possible.

  19. Genome-wide association study for jumping performances in French sport horses.

    PubMed

    Brard, S; Ricard, A

    2015-02-01

    A genome-wide association study was performed to identify single nucleotide polymorphisms (SNPs) associated with jumping performances of warmbloods in France. The 999 horses included in the study for jumping performances were sport horses [mostly Selle Français (68%), Anglo-Arabians (13%) and horses from the other European studbooks]. Horses were genotyped using the Illumina EquineSNP50 BeadChip. Of the 54,602 SNPs available on this chip, 44,424 were retained after quality testing. Phenotypes were obtained by deregressing official breeding values for jumping competitions to use all available information, that is, the performances of each horse as well as those of its relatives. Two models were used to test the effects of the genotypes on deregressed phenotypes: a single-marker mixed model and a haplotype-based mixed model (significant: P < 1E-05; suggestive: P < 1E-04). Both models included a polygenic effect to take into account familial structures. For jumping performances, one suggestive quantitative trait locus (QTL) located on chromosome 1 (BIEC2_31196 and BIEC2_31198) was detected with both models. This QTL explains 0.7% of the phenotypic variance. RYR2, a gene encoding a major calcium channel in cardiac muscle in humans and mice, is located 0.55 Mb from this potential QTL. PMID:25515185

  20. Beef cattle body temperature during climatic stress: a genome-wide association study.

    PubMed

    Howard, Jeremy T; Kachman, Stephen D; Snelling, Warren M; Pollak, E John; Ciobanu, Daniel C; Kuehn, Larry A; Spangler, Matthew L

    2014-09-01

    Cattle are reared in diverse environments and collecting phenotypic body temperature (BT) measurements to characterize BT variation across diverse environments is difficult and expensive. To better understand the genetic basis of BT regulation, a genome-wide association study was conducted utilizing crossbred steers and heifers totaling 239 animals of unknown pedigree and breed fraction. During predicted extreme heat and cold stress events, hourly tympanic and vaginal BT devices were placed in steers and heifers, respectively. Individuals were genotyped with the BovineSNP50K_v2 assay and data analyzed using Bayesian models for area under the curve (AUC), a measure of BT over time, using hourly BT observations summed across 5-days (AUC summer 5-day (AUCS5D) and AUC winter 5-day (AUCW5D)). Posterior heritability estimates were moderate to high and were estimated to be 0.68 and 0.21 for AUCS5D and AUCW5D, respectively. Moderately positive correlations between direct genomic values for AUCS5D and AUCW5D (0.40) were found, although a small percentage of the top 5% 1-Mb windows were in common. Different sets of genes were associated with BT during winter and summer, thus simultaneous selection for animals tolerant to both heat and cold appears possible. PMID:24362770

  1. Genome-wide association mapping of cadmium accumulation in different organs of barley.

    PubMed

    Wu, Dezhi; Sato, Kazuhiro; Ma, Jian Feng

    2015-11-01

    The threshold value of cadmium (Cd) concentration in grains of barley (Hordeum vulgare) is the lowest among cereal crops; however, it is poorly understood how Cd accumulation in barley grain is genetically controlled. We investigated genotypic variation in Cd accumulation of different organs in 100 accessions from a subset of the barley core collection using both hydroponic and Cd-contaminated soil culture. We also performed a genome-wide association (GWA) mapping for Cd accumulation in different organs. A large genotypic variation in the Cd concentration was found in all organs. There was a good correlation between shoot Cd of solution and soil culture, the shoot Cd and grain Cd, but no correlation between the root Cd and grain Cd. GWA mapping detected 9 quantitative trait loci (QTL) for root Cd, 21 for shoot Cd, 14 for root-to-shoot translocation and 15 for grain Cd. A common QTL for the shoot Cd and root-to-shoot translocation was found at 132.6 cM on chromosome 5H. Two major QTL for grain Cd were identified on chromosome 2H and chromosome 5H. The genetic variation in Cd accumulation and major QTL detected provide useful information helpful for cloning candidate genes for Cd accumulation and breeding low-Cd barley cultivars in future. PMID:26061418

  2. Genome-Wide Association Study of a Varroa-Specific Defense Behavior in Honeybees (Apis mellifera).

    PubMed

    Spötter, Andreas; Gupta, Pooja; Mayer, Manfred; Reinsch, Norbert; Bienefeld, Kaspar

    2016-05-01

    Honey bees are exposed to many damaging pathogens and parasites. The most devastating is Varroa destructor, which mainly affects the brood. A promising approach for preventing its spread is to breed Varroa-resistant honey bees. One trait that has been shown to provide significant resistance against the Varroa mite is hygienic behavior, which is a behavioral response of honeybee workers to brood diseases in general. Here, we report the use of an Affymetrix 44K SNP array to analyze SNPs associated with detection and uncapping of Varroa-parasitized brood by individual worker bees (Apis mellifera). For this study, 22 000 individually labeled bees were video-monitored and a sample of 122 cases and 122 controls was collected and analyzed to determine the dependence/independence of SNP genotypes from hygienic and nonhygienic behavior on a genome-wide scale. After false-discovery rate correction of the P values, 6 SNP markers had highly significant associations with the trait investigated (α < 0.01). Inspection of the genomic regions around these SNPs led to the discovery of putative candidate genes. PMID:26774061

  3. Identification and characterization of a genome-wide significant region associated with red blood cell phenotypes in domestic sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome wide association study (GWAS) investigating red blood cell (RBC) phenotypes was performed with over 500 domestic sheep (Ovis aries) from three economically important breeds in the US (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism (SNP, hereafter the discovery SNP) sh...

  4. Genome-wide SNP discovery in walnut with an AGSNP pipeline updated for SNP discovery in allogamous organisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: A genome-wide set of single nucleotide polymorphisms (SNPs) is a valuable resource in genetic research and breeding and is usually developed by re-sequencing a genome. If a genome sequence is not available, an alternative strategy must be used. We previously reported the development of a...

  5. Genome-wide SNP discovery in walnut with an AGSNP pipeline updated for SNP discovery in allogamous organisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background A genome-wide set of single nucleotide polymorphisms (SNPs) is a valuable resource in genetic research and breeding and is usually developed by re-sequencing a genome. If a genome sequence is not available, an alternative strategy must be used. We previously reported the development of a ...

  6. Genome-wide association mapping of fusarium head blight resistance in wheat (Triticum aestivum L.) using genotyping by sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB) is one of the most important wheat diseases worldwide and host resistance displays complex genetic control. A genome-wide association study (GWAS) was performed on 273 winter wheat breeding lines from the mid-western and eastern regions of the US to identify chromosomal re...

  7. Estimated breeding values for meat characteristics of crossbred cattle with an animal model.

    PubMed

    Van Vleck, L D; Hakim, A F; Cundiff, L V; Koch, R M; Crouse, J D; Boldman, K G

    1992-02-01

    Longissimus muscle area, shear force measure, and sensory panel scores for flavor, juiciness, and tenderness, and marbling score were obtained from 682 steer carcasses, resulting from crosses among five Bos taurus and Bos indicus breeds. The single-trait model used included birth year and as covariates breed fractions, weaning age, and days on feed. The numerator relationship matrix was for 1,350 animals (682 steers, 74 pure breed and 52 F1-cross sires and 542 dams). The coefficient matrix was inverted to examine standard errors of prediction. Estimated breeding value is the sum of the estimate of genetic deviation and the weighted (fractions) sum of estimates of breed effects. Heritabilities used in estimating breeding values were .62, .06, .05, .11, .05, and .43 for longissimus muscle area, shear force, flavor, juiciness, tenderness, and marbling score. Sires within a breed or crossbred group tended to rank similarly due to large differences among breed effects (e.g., the six Sahiwal sires ranked in the highest six places for shear force). These results illustrate that for traits with large breed differences, selection of the proper breed should be done before selection within that breed. PMID:1548197

  8. Genome-Wide Association Study of Insect Bite Hypersensitivity in Swedish-Born Icelandic Horses.

    PubMed

    Shrestha, Merina; Eriksson, Susanne; Schurink, Anouk; Andersson, Lisa S; Sundquist, Marie; Frey, Rebecka; Broström, Hans; Bergström, Tomas; Ducro, Bart; Lindgren, Gabriella

    2015-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial value of the horse. It is a multifactorial disorder influenced by both genetic and environmental factors, with heritability ranging from 0.16 to 0.27 in various horse breeds. The worldwide prevalence in different horse breeds ranges from 3% to 60%; it is more than 50% in Icelandic horses exported to the European continent and approximately 8% in Swedish-born Icelandic horses. To minimize the influence of environmental effects, we analyzed Swedish-born Icelandic horses to identify genomic regions that regulate susceptibility to IBH. We performed a genome-wide association (GWA) study on 104 affected and 105 unaffected Icelandic horses genotyped using Illumina® EquineSNP50 Genotyping BeadChip. Quality control and population stratification analyses were performed with the GenABEL package in R (λ = 0.81). The association analysis was performed using the Bayesian variable selection method, Bayes C, implemented in GenSel software. The highest percentage of genetic variance was explained by the windows on X chromosomes (0.51% and 0.36% by 73 and 74 mb), 17 (0.34% by 77 mb), and 18 (0.34% by 26 mb). Overlapping regions with previous GWA studies were observed on chromosomes 7, 9, and 17. The windows identified in our study on chromosomes 7, 10, and 17 harbored immune system genes and are priorities for further investigation. PMID:26026046

  9. Genome-Wide Association for Growth Traits in Canchim Beef Cattle

    PubMed Central

    Buzanskas, Marcos E.; Grossi, Daniela A.; Ventura, Ricardo V.; Schenkel, Flávio S.; Sargolzaei, Mehdi; Meirelles, Sarah L. C.; Mokry, Fabiana B.; Higa, Roberto H.; Mudadu, Maurício A.; da Silva, Marcos V. G. Barbosa.; Niciura, Simone C. M.; Júnior, Roberto A. A. Torres.; Alencar, Maurício M.; Regitano, Luciana C. A.; Munari, Danísio P.

    2014-01-01

    Studies are being conducted on the applicability of genomic data to improve the accuracy of the selection process in livestock, and genome-wide association studies (GWAS) provide valuable information to enhance the understanding on the genetics of complex traits. The aim of this study was to identify genomic regions and genes that play roles in birth weight (BW), weaning weight adjusted for 210 days of age (WW), and long-yearling weight adjusted for 420 days of age (LYW) in Canchim cattle. GWAS were performed by means of the Generalized Quasi-Likelihood Score (GQLS) method using genotypes from the BovineHD BeadChip and estimated breeding values for BW, WW, and LYW. Data consisted of 285 animals from the Canchim breed and 114 from the MA genetic group (derived from crossings between Charolais sires and ½ Canchim + ½ Zebu dams). After applying a false discovery rate correction at a 10% significance level, a total of 4, 12, and 10 SNPs were significantly associated with BW, WW, and LYW, respectively. These SNPs were surveyed to their corresponding genes or to surrounding genes within a distance of 250 kb. The genes DPP6 (dipeptidyl-peptidase 6) and CLEC3B (C-type lectin domain family 3 member B) were highlighted, considering its functions on the development of the brain and skeletal system, respectively. The GQLS method identified regions on chromosome associated with birth weight, weaning weight, and long-yearling weight in Canchim and MA animals. New candidate regions for body weight traits were detected and some of them have interesting biological functions, of which most have not been previously reported. The observation of QTL reports for body weight traits, covering areas surrounding the genes (SNPs) herein identified provides more evidence for these associations. Future studies targeting these areas could provide further knowledge to uncover the genetic architecture underlying growth traits in Canchim cattle. PMID:24733441

  10. Genome-wide association for heifer reproduction and calf performance traits in beef cattle.

    PubMed

    Akanno, Everestus C; Plastow, Graham; Fitzsimmons, Carolyn; Miller, Stephen P; Baron, Vern; Ominski, Kimberly; Basarab, John A

    2015-12-01

    The aim of this study was to identify SNP markers that associate with variation in beef heifer reproduction and performance of their calves. A genome-wide association study was performed by means of the generalized quasi-likelihood score (GQLS) method using heifer genotypes from the BovineSNP50 BeadChip and estimated breeding values for pre-breeding body weight (PBW), pregnancy rate (PR), calving difficulty (CD), age at first calving (AFC), calf birth weight (BWT), calf weaning weight (WWT), and calf pre-weaning average daily gain (ADG). Data consisted of 785 replacement heifers from three Canadian research herds, namely Brandon Research Centre, Brandon, Manitoba, University of Alberta Roy Berg Kinsella Ranch, Kinsella, Alberta, and Lacombe Research Centre, Lacombe, Alberta. After applying a false discovery rate correction at a 5% significance level, a total of 4, 3, 3, 9, 6, 2, and 1 SNPs were significantly associated with PBW, PR, CD, AFC, BWT, WWT, and ADG, respectively. These SNPs were located on chromosomes 1, 5-7, 9, 13-16, 19-21, 24, 25, and 27-29. Chromosomes 1, 5, and 24 had SNPs with pleiotropic effects. New significant SNPs that impact functional traits were detected, many of which have not been previously reported. The results of this study support quantitative genetic studies related to the inheritance of these traits, and provides new knowledge regarding beef cattle quantitative trait loci effects. The identification of these SNPs provides a starting point to identify genes affecting heifer reproduction traits and performance of their calves (BWT, WWT, and ADG). They also contribute to a better understanding of the biology underlying these traits and will be potentially useful in marker- and genome-assisted selection and management. PMID:26484575

  11. Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats

    PubMed Central

    Martin, Pauline Marie; Palhière, Isabelle; Ricard, Anne; Tosser-Klopp, Gwenola; Rupp, Rachel

    2016-01-01

    This paper reports a quantitative genetics and genomic analysis of undesirable coat color patterns in goats. Two undesirable coat colors have routinely been recorded for the past 15 years in French Saanen goats. One fifth of Saanen females have been phenotyped “pink” (8.0%) or “pink neck” (11.5%) and consequently have not been included in the breeding program as elite animals. Heritability of the binary “pink” and “pink neck” phenotype, estimated from 103,443 females was 0.26 for “pink” and 0.21 for “pink neck”. Genome wide association studies (using haplotypes or single SNPs) were implemented using a daughter design of 810 Saanen goats sired by 9 Artificial Insemination bucks genotyped with the goatSNP50 chip. A highly significant signal (-log10pvalue = 10.2) was associated with the “pink neck” phenotype on chromosome 11, suggesting the presence of a major gene. Highly significant signals for the “pink” phenotype were found on chromosomes 5 and 13 (-log10p values of 7.2 and, 7.7 respectively). The most significant SNP on chromosome 13 was in the ASIP gene region, well known for its association with coat color phenotypes. Nine significant signals were also found for both traits. The highest signal for each trait was detected by both single SNP and haplotype approaches, whereas the smaller signals were not consistently detected by the two methods. Altogether these results demonstrated a strong genetic control of the “pink” and “pink neck” phenotypes in French Saanen goats suggesting that SNP information could be used to identify and remove undesired colored animals from the breeding program. PMID:27030980

  12. Genome-wide Association Study and Meta-Analysis Identify ISL1 as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy

    PubMed Central

    Draaken, Markus; Knapp, Michael; Pennimpede, Tracie; Schmidt, Johanna M.; Ebert, Anne-Karolin; Rösch, Wolfgang; Stein, Raimund; Utsch, Boris; Hirsch, Karin; Boemers, Thomas M.; Mangold, Elisabeth; Heilmann, Stefanie; Ludwig, Kerstin U.; Jenetzky, Ekkehart; Zwink, Nadine; Moebus, Susanne; Herrmann, Bernhard G.; Mattheisen, Manuel; Nöthen, Markus M.

    2015-01-01

    The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region. PMID:25763902

  13. Genome wide signatures of positive selection: The comparison of independent samples and the identification of regions associated to traits

    PubMed Central

    Barendse, William; Harrison, Blair E; Bunch, Rowan J; Thomas, Merle B; Turner, Lex B

    2009-01-01

    Background The goal of genome wide analyses of polymorphisms is to achieve a better understanding of the link between genotype and phenotype. Part of that goal is to understand the selective forces that have operated on a population. Results In this study we compared the signals of selection, identified through population divergence in the Bovine HapMap project, to those found in an independent sample of cattle from Australia. Evidence for population differentiation across the genome, as measured by FST, was highly correlated in the two data sets. Nevertheless, 40% of the variance in FST between the two studies was attributed to the differences in breed composition. Seventy six percent of the variance in FST was attributed to differences in SNP composition and density when the same breeds were compared. The difference between FST of adjacent loci increased rapidly with the increase in distance between SNP, reaching an asymptote after 20 kb. Using 129 SNP that have highly divergent FST values in both data sets, we identified 12 regions that had additive effects on the traits residual feed intake, beef yield or intramuscular fatness measured in the Australian sample. Four of these regions had effects on more than one trait. One of these regions includes the R3HDM1 gene, which is under selection in European humans. Conclusion Firstly, many different populations will be necessary for a full description of selective signatures across the genome, not just a small set of highly divergent populations. Secondly, it is necessary to use the same SNP when comparing the signatures of selection from one study to another. Thirdly, useful signatures of selection can be obtained where many of the groups have only minor genetic differences and may not be clearly separated in a principal component analysis. Fourthly, combining analyses of genome wide selection signatures and genome wide associations to traits helps to define the trait under selection or the population group in which

  14. Genome-Wide Association Mapping of Anther Extrusion in Hexaploid Spring Wheat.

    PubMed

    Muqaddasi, Quddoos H; Lohwasser, Ulrike; Nagel, Manuela; Börner, Andreas; Pillen, Klaus; Röder, Marion S

    2016-01-01

    In a number of crop species hybrids are able to outperform line varieties. The anthers of the autogamous bread wheat plant are normally extruded post anthesis, a trait which is unfavourable for the production of F1 hybrid grain. Higher anther extrusion (AE) promotes cross fertilization for more efficient hybrid seed production. Therefore, this study aimed at the genetic dissection of AE by genome wide association studies (GWAS) and determination of the main effect QTL. We applied GWAS approach to identify DArT markers potentially linked to AE to unfold its genetic basis in a panel of spring wheat accessions. Phenotypic data were collected for three years and best linear unbiased estimate (BLUE) values were calculated across all years. The extent of the AE correlation between growing years and BLUE values ranged from r = +0.56 (2013 vs 2015) to 0.91 (2014 vs BLUE values). The broad sense heritability was 0.84 across all years. Six accessions displayed stable AE >80% across all the years. Genotyping data included 2,575 DArT markers (with minimum of 0.05 minor allele frequency applied). AE was influenced both by genotype and by the growing environment. In all, 131 significant marker trait associations (MTAs) (|log10 (P)| >FDR) were established for AE. AE behaved as a quantitative trait, with five consistently significant markers (significant across at least two years with a significant BLUE value) contributing a minor to modest proportion (4.29% to 8.61%) of the phenotypic variance and affecting the trait either positively or negatively. For this reason, there is potential for breeding for improved AE by gene pyramiding. The consistently significant markers linked to AE could be helpful for marker assisted selection to transfer AE to high yielding varieties allowing to promote the exploitation of hybrid-heterosis in the key crop wheat. PMID:27191600

  15. Genome-Wide Association Mapping of Anther Extrusion in Hexaploid Spring Wheat

    PubMed Central

    Muqaddasi, Quddoos H.; Lohwasser, Ulrike; Nagel, Manuela; Börner, Andreas; Pillen, Klaus; Röder, Marion S.

    2016-01-01

    In a number of crop species hybrids are able to outperform line varieties. The anthers of the autogamous bread wheat plant are normally extruded post anthesis, a trait which is unfavourable for the production of F1 hybrid grain. Higher anther extrusion (AE) promotes cross fertilization for more efficient hybrid seed production. Therefore, this study aimed at the genetic dissection of AE by genome wide association studies (GWAS) and determination of the main effect QTL. We applied GWAS approach to identify DArT markers potentially linked to AE to unfold its genetic basis in a panel of spring wheat accessions. Phenotypic data were collected for three years and best linear unbiased estimate (BLUE) values were calculated across all years. The extent of the AE correlation between growing years and BLUE values ranged from r = +0.56 (2013 vs 2015) to 0.91 (2014 vs BLUE values). The broad sense heritability was 0.84 across all years. Six accessions displayed stable AE >80% across all the years. Genotyping data included 2,575 DArT markers (with minimum of 0.05 minor allele frequency applied). AE was influenced both by genotype and by the growing environment. In all, 131 significant marker trait associations (MTAs) (|log10 (P)| >FDR) were established for AE. AE behaved as a quantitative trait, with five consistently significant markers (significant across at least two years with a significant BLUE value) contributing a minor to modest proportion (4.29% to 8.61%) of the phenotypic variance and affecting the trait either positively or negatively. For this reason, there is potential for breeding for improved AE by gene pyramiding. The consistently significant markers linked to AE could be helpful for marker assisted selection to transfer AE to high yielding varieties allowing to promote the exploitation of hybrid-heterosis in the key crop wheat. PMID:27191600

  16. Genome-Wide Scan Reveals Mutation Associated with Melanoma

    MedlinePlus

    ... 1999 Spotlight on Research 2012 July 2012 (historical) Genome-Wide Scan Reveals Mutation Associated with Melanoma A ... out to see if a technology called whole genome sequencing would help them find other genetic risk ...

  17. Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds

    PubMed Central

    Shin, Dong-Hyun; Lee, Jin Woo; Park, Jong-Eun; Choi, Ik-Young; Oh, Hee-Seok; Kim, Hyeon Jeong; Kim, Heebal

    2015-01-01

    Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds. PMID:25925054

  18. Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds.

    PubMed

    Shin, Dong-Hyun; Lee, Jin Woo; Park, Jong-Eun; Choi, Ik-Young; Oh, Hee-Seok; Kim, Hyeon Jeong; Kim, Heebal

    2015-06-01

    Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds. PMID:25925054

  19. Genome-wide Mapping Reveals Conservation of Promoter DNA Methylation Following Chicken Domestication

    PubMed Central

    Li, Qinghe; Wang, Yuanyuan; Hu, Xiaoxiang; Zhao, Yaofeng; Li, Ning

    2015-01-01

    It is well-known that environment influences DNA methylation, however, the extent of heritable DNA methylation variation following animal domestication remains largely unknown. Using meDIP-chip we mapped the promoter methylomes for 23,316 genes in muscle tissues of ancestral and domestic chickens. We systematically examined the variation of promoter DNA methylation in terms of different breeds, differentially expressed genes, SNPs and genes undergo genetic selection sweeps. While considerable changes in DNA sequence and gene expression programs were prevalent, we found that the inter-strain DNA methylation patterns were highly conserved in promoter region between the wild and domestic chicken breeds. Our data suggests a global preservation of DNA methylation between the wild and domestic chicken breeds in either a genome-wide or locus-specific scale in chick muscle tissues. PMID:25735894

  20. Genome wide identification of regulatory motifs in Bacillus subtilis

    PubMed Central

    Mwangi, Michael M; Siggia, Eric D

    2003-01-01

    Background To explain the vastly different phenotypes exhibited by the same organism under different conditions, it is essential that we understand how the organism's genes are coordinately regulated. While there are many excellent tools for predicting sequences encoding proteins or RNA genes, few algorithms exist to predict regulatory sequences on a genome wide scale with no prior information. Results To identify motifs involved in the control of transcription, an algorithm was developed that searches upstream of operons for improbably frequent dimers. The algorithm was applied to the B. subtilis genome, which is predicted to encode for approximately 200 DNA binding proteins. The dimers found to be over-represented could be clustered into 317 distinct groups, each thought to represent a class of motifs uniquely recognized by some transcription factor. For each cluster of dimers, a representative weight matrix was derived and scored over the regions upstream of the operons to predict the sites recognized by the cluster's factor, and a putative regulon of the operons immediately downstream of the sites was inferred. The distribution in number of operons per predicted regulon is comparable to that for well characterized transcription factors. The most highly over-represented dimers matched σA, the T-box, and σW sites. We have evidence to suggest that at least 52 of our clusters of dimers represent actual regulatory motifs, based on the groups' weight matrix matches to experimentally characterized sites, the functional similarity of the component operons of the groups' regulons, and the positional biases of the weight matrix matches. All predictions are assigned a significance value, and thresholds are set to avoid false positives. Where possible, we examine our false negatives, drawing examples from known regulatory motifs and regulons inferred from RNA expression data. Conclusions We have demonstrated that in the case of B. subtilis our algorithm allows for the

  1. Genome-wide association scan suggests basis for microtia in Awassi sheep.

    PubMed

    Jawasreh, K; Boettcher, P J; Stella, A

    2016-08-01

    Hereditary underdevelopment of the ear, a condition also known as microtia, has been observed in several sheep breeds as well as in humans and other species. Its genetic basis in sheep is unknown. The Awassi sheep, a breed native to southwest Asia, carries this phenotype and was targeted for molecular characterization via a genome-wide association study. DNA samples were collected from sheep in Jordan. Eight affected and 12 normal individuals were genotyped with the Illumina OvineSNP50(®) chip. Multilocus analyses failed to identify any genotypic association. In contrast, a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago. Many of the earless sheep breeds may thus share the causative mutation, especially within the subgroup of fat-tailed, wool sheep. PMID:26990958

  2. Sparse principal component analysis for identifying ancestry-informative markers in genome-wide association studies.

    PubMed

    Lee, Seokho; Epstein, Michael P; Duncan, Richard; Lin, Xihong

    2012-05-01

    Genome-wide association studies (GWAS) routinely apply principal component analysis (PCA) to infer population structure within a sample to correct for confounding due to ancestry. GWAS implementation of PCA uses tens of thousands of single-nucleotide polymorphisms (SNPs) to infer structure, despite the fact that only a small fraction of such SNPs provides useful information on ancestry. The identification of this reduced set of ancestry-informative markers (AIMs) from a GWAS has practical value; for example, researchers can genotype the AIM set to correct for potential confounding due to ancestry in follow-up studies that utilize custom SNP or sequencing technology. We propose a novel technique to identify AIMs from genome-wide SNP data using sparse PCA. The procedure uses penalized regression methods to identify those SNPs in a genome-wide panel that significantly contribute to the principal components while encouraging SNPs that provide negligible loadings to vanish from the analysis. We found that sparse PCA leads to negligible loss of ancestry information compared to traditional PCA analysis of genome-wide SNP data. We further demonstrate the value of sparse PCA for AIM selection using real data from the International HapMap Project and a genomewide study of inflammatory bowel disease. We have implemented our approach in open-source R software for public use. PMID:22508067

  3. Genome wide association scan for chronic periodontitis implicates novel locus

    PubMed Central

    2014-01-01

    Background There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99). Methods Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed. Results The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis. Conclusions Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. PMID:25008200

  4. Genome-Wide Association Study of Grain Appearance and Milling Quality in a Worldwide Collection of Indica Rice Germplasm.

    PubMed

    Qiu, Xianjin; Pang, Yunlong; Yuan, Zhihua; Xing, Danying; Xu, Jianlong; Dingkuhn, Michael; Li, Zhikang; Ye, Guoyou

    2015-01-01

    Grain appearance quality and milling quality are the main determinants of market value of rice. Breeding for improved grain quality is a major objective of rice breeding worldwide. Identification of genes/QTL controlling quality traits is the prerequisite for increasing breeding efficiency through marker-assisted selection. Here, we reported a genome-wide association study in indica rice to identify QTL associated with 10 appearance and milling quality related traits, including grain length, grain width, grain length to width ratio, grain thickness, thousand grain weight, degree of endosperm chalkiness, percentage of grains with chalkiness, brown rice rate, milled rice rate and head milled rice rate. A diversity panel consisting of 272 indica accessions collected worldwide was evaluated in four locations including Hangzhou, Jingzhou, Sanya and Shenzhen representing indica rice production environments in China and genotyped using genotyping-by-sequencing and Diversity Arrays Technology based on next-generation sequencing technique called DArTseq™. A wide range of variation was observed for all traits in all environments. A total of 16 different association analysis models were compared to determine the best model for each trait-environment combination. Association mapping based on 18,824 high quality markers yielded 38 QTL for the 10 traits. Five of the detected QTL corresponded to known genes or fine mapped QTL. Among the 33 novel QTL identified, qDEC1.1 (qGLWR1.1), qBRR2.2 (qGL2.1), qTGW2.1 (qGL2.2), qGW11.1 (qMRR11.1) and qGL7.1 affected multiple traits with relatively large effects and/or were detected in multiple environments. The research provided an insight of the genetic architecture of rice grain quality and important information for mining genes/QTL with large effects within indica accessions for rice breeding. PMID:26714258

  5. Genome-Wide Association Study of Grain Appearance and Milling Quality in a Worldwide Collection of Indica Rice Germplasm

    PubMed Central

    Yuan, Zhihua; Xing, Danying; Xu, Jianlong; Dingkuhn, Michael; Li, Zhikang; Ye, Guoyou

    2015-01-01

    Grain appearance quality and milling quality are the main determinants of market value of rice. Breeding for improved grain quality is a major objective of rice breeding worldwide. Identification of genes/QTL controlling quality traits is the prerequisite for increasing breeding efficiency through marker-assisted selection. Here, we reported a genome-wide association study in indica rice to identify QTL associated with 10 appearance and milling quality related traits, including grain length, grain width, grain length to width ratio, grain thickness, thousand grain weight, degree of endosperm chalkiness, percentage of grains with chalkiness, brown rice rate, milled rice rate and head milled rice rate. A diversity panel consisting of 272 indica accessions collected worldwide was evaluated in four locations including Hangzhou, Jingzhou, Sanya and Shenzhen representing indica rice production environments in China and genotyped using genotyping-by-sequencing and Diversity Arrays Technology based on next-generation sequencing technique called DArTseq™. A wide range of variation was observed for all traits in all environments. A total of 16 different association analysis models were compared to determine the best model for each trait-environment combination. Association mapping based on 18,824 high quality markers yielded 38 QTL for the 10 traits. Five of the detected QTL corresponded to known genes or fine mapped QTL. Among the 33 novel QTL identified, qDEC1.1 (qGLWR1.1), qBRR2.2 (qGL2.1), qTGW2.1 (qGL2.2), qGW11.1 (qMRR11.1) and qGL7.1 affected multiple traits with relatively large effects and/or were detected in multiple environments. The research provided an insight of the genetic architecture of rice grain quality and important information for mining genes/QTL with large effects within indica accessions for rice breeding. PMID:26714258

  6. Genome-wide association for grain morphology in synthetic hexaploid wheats using digital imaging analysis

    PubMed Central

    2014-01-01

    with TKW, grain width and thickness. In silico functional analysis predicted a range of biological functions for 32 DArT loci and receptor like kinase, known to affect plant development, appeared to be common protein family encoded by several loci responsible for grain size and shape. Conclusion Conclusively, we demonstrated the application and integration of multiple approaches including high throughput phenotyping using DI, genome wide association studies (GWAS) and in silico functional analysis of candidate loci to analyze target traits, and identify candidate genomic regions underlying these traits. These approaches provided great opportunity to understand the breeding value of SHWs for improving grain weight and enhanced our deep understanding on molecular genetics of grain weight in wheat. PMID:24884376

  7. Assisted Breeding in Sugar Beet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular insight and methods applied to plant breeding and germplasm enhancement is the goal of assisted breeding, also known as marker assisted breeding, marker assisted selection, molecular plant breeding, or genome-wide selection, among others. The basic idea is that most, if not all, heritable ...

  8. Genome-wide mining, characterization, and development of microsatellite markers in Marsupenaeus japonicus by genome survey sequencing

    NASA Astrophysics Data System (ADS)

    Lu, Xia; Luan, Sheng; Kong, Jie; Hu, Longyang; Mao, Yong; Zhong, Shengping

    2015-12-01

    The kuruma prawn, Marsupenaeus japonicus, is one of the most cultivated and consumed species of shrimp. However, very few molecular genetic/genomic resources are publically available for it. Thus, the characterization and distribution of simple sequence repeats (SSRs) remains ambiguous and the use of SSR markers in genomic studies and marker-assisted selection is limited. The goal of this study is to characterize and develop genome-wide SSR markers in M. japonicus by genome survey sequencing for application in comparative genomics and breeding. A total of 326 945 perfect SSRs were identifi ed, among which dinucleotide repeats were the most frequent class (44.08%), followed by mononucleotides (29.67%), trinucleotides (18.96%), tetranucleotides (5.66%), hexanucleotides (1.07%), and pentanucleotides (0.56%). In total, 151 541 SSR loci primers were successfully designed. A subset of 30 SSR primer pairs were synthesized and tested in 42 individuals from a wild population, of which 27 loci (90.0%) were successfully amplifi ed with specifi c products and 24 (80.0%) were polymorphic. For the amplifi ed polymorphic loci, the alleles ranged from 5 to 17 (with an average of 9.63), and the average PIC value was 0.796. A total of 58 256 SSR-containing sequences had signifi cant Gene Ontology annotation; these are good functional molecular marker candidates for association studies and comparative genomic analysis. The newly identifi ed SSRs signifi cantly contribute to the M. japonicus genomic resources and will facilitate a number of genetic and genomic studies, including high density linkage mapping, genome-wide association analysis, marker-aided selection, comparative genomics analysis, population genetics, and evolution.

  9. Assessing statistical significance in multivariable genome wide association analysis

    PubMed Central

    Buzdugan, Laura; Kalisch, Markus; Navarro, Arcadi; Schunk, Daniel; Fehr, Ernst; Bühlmann, Peter

    2016-01-01

    Motivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS. Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whether or not a SNP carries any additional information about the phenotype beyond that available by all the other SNPs. This rules out spurious correlations between phenotypes and SNPs that can arise from marginal methods because the ‘spuriously correlated’ SNP merely happens to be correlated with the ‘truly causal’ SNP. In addition, the method offers a data driven approach to identifying and refining groups of SNPs that jointly contain informative signals about the phenotype. We demonstrate the value of our method by applying it to the seven diseases analyzed by the Wellcome Trust Case Control Consortium (WTCCC). We show, in particular, that our method is also capable of finding significant SNPs that were not identified in the original WTCCC study, but were replicated in other independent studies. Availability and implementation: Reproducibility of our research is supported by the open-source Bioconductor package hierGWAS. Contact: peter.buehlmann@stat.math.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153677

  10. The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population

    PubMed Central

    Otowa, Takeshi; Kawamura, Yoshiya; Tsutsumi, Akizumi; Kawakami, Norito; Kan, Chiemi; Shimada, Takafumi; Umekage, Tadashi; Kasai, Kiyoto; Tokunaga, Katsushi; Sasaki, Tsukasa

    2016-01-01

    Stressful events have been identified as a risk factor for depression. Although gene–environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10−8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS. PMID:27529621

  11. The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population.

    PubMed

    Otowa, Takeshi; Kawamura, Yoshiya; Tsutsumi, Akizumi; Kawakami, Norito; Kan, Chiemi; Shimada, Takafumi; Umekage, Tadashi; Kasai, Kiyoto; Tokunaga, Katsushi; Sasaki, Tsukasa

    2016-01-01

    Stressful events have been identified as a risk factor for depression. Although gene-environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10-8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS. PMID:27529621

  12. A super powerful method for genome wide association study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-Wide Association Studies shed light on the identification of genes underlying human diseases and agriculturally important traits. This potential has been shadowed by false positive findings. The Mixed Linear Model (MLM) method is flexible enough to simultaneously incorporate population struct...

  13. Design and bioinformatics analysis of genome-wide CLIP experiments

    PubMed Central

    Wang, Tao; Xiao, Guanghua; Chu, Yongjun; Zhang, Michael Q.; Corey, David R.; Xie, Yang

    2015-01-01

    The past decades have witnessed a surge of discoveries revealing RNA regulation as a central player in cellular processes. RNAs are regulated by RNA-binding proteins (RBPs) at all post-transcriptional stages, including splicing, transportation, stabilization and translation. Defects in the functions of these RBPs underlie a broad spectrum of human pathologies. Systematic identification of RBP functional targets is among the key biomedical research questions and provides a new direction for drug discovery. The advent of cross-linking immunoprecipitation coupled with high-throughput sequencing (genome-wide CLIP) technology has recently enabled the investigation of genome-wide RBP–RNA binding at single base-pair resolution. This technology has evolved through the development of three distinct versions: HITS-CLIP, PAR-CLIP and iCLIP. Meanwhile, numerous bioinformatics pipelines for handling the genome-wide CLIP data have also been developed. In this review, we discuss the genome-wide CLIP technology and focus on bioinformatics analysis. Specifically, we compare the strengths and weaknesses, as well as the scopes, of various bioinformatics tools. To assist readers in choosing optimal procedures for their analysis, we also review experimental design and procedures that affect bioinformatics analyses. PMID:25958398

  14. Genome-wide association study identifies five new schizophrenia loci

    PubMed Central

    2012-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9). PMID:21926974

  15. Genome-wide characterization of maize miRNA genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in plant growth and development. We conducted a genome-wide survey of maize miRNA genes, characterizing their structure, expression, and evolution. Computational approaches based on homology and secondary structure modeling ident...

  16. Genome-wide association mapping of soybean aphid resistance traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean aphid is the most damaging insect pest of soybean in the Upper Midwest and is primarily controlled by insecticides. Soybean aphid resistance (i.e., Rag genes) has been documented in some soybean lines at chromosomes 6, 7, 13, and 16, but more sources of resistance are needed. Genome-wide ass...

  17. Hot topic: Definition and implementation of a breeding value for feed efficiency in dairy cows.

    PubMed

    Pryce, J E; Gonzalez-Recio, O; Nieuwhof, G; Wales, W J; Coffey, M P; Hayes, B J; Goddard, M E

    2015-10-01

    A new breeding value that combines the amount of feed saved through improved metabolic efficiency with predicted maintenance requirements is described. The breeding value includes a genomic component for residual feed intake (RFI) combined with maintenance requirements calculated from either a genomic or pedigree estimated breeding value (EBV) for body weight (BW) predicted using conformation traits. Residual feed intake is only available for genotyped Holsteins; however, BW is available for all breeds. The RFI component of the "feed saved" EBV has 2 parts: Australian calf RFI and Australian lactating cow RFI. Genomic breeding values for RFI were estimated from a reference population of 2,036 individuals in a multi-trait analysis including Australian calf RFI (n=843), Australian lactating cow RFI (n=234), and UK and Dutch lactating cow RFI (n=958). In all cases, the RFI phenotypes were deviations from a mean of 0, calculated by correcting dry matter intake for BW, growth, and milk yield (in the case of lactating cows). Single nucleotide polymorphism effects were calculated from the output of genomic BLUP and used to predict breeding values of 4,106 Holstein sires that were genotyped but did not have RFI phenotypes themselves. These bulls already had BW breeding values calculated from type traits, from which maintenance requirements in kilograms of feed per year were inferred. Finally, RFI and the feed required for maintenance (through BW) were used to calculate a feed saved breeding value and expressed as the predicted amount of feed saved per year. Animals that were 1 standard deviation above the mean were predicted to eat 66 kg dry matter less per year at the same level of milk production. In a data set of genotyped Holstein sires, the mean reliability of the feed saved breeding value was 0.37. For Holsteins that are not genotyped and for breeds other than Holsteins, feed saved is calculated using BW only. From April 2015, feed saved has been included as part of

  18. Massively expedited genome-wide heritability analysis (MEGHA).

    PubMed

    Ge, Tian; Nichols, Thomas E; Lee, Phil H; Holmes, Avram J; Roffman, Joshua L; Buckner, Randy L; Sabuncu, Mert R; Smoller, Jordan W

    2015-02-24

    The discovery and prioritization of heritable phenotypes is a computational challenge in a variety of settings, including neuroimaging genetics and analyses of the vast phenotypic repositories in electronic health record systems and population-based biobanks. Classical estimates of heritability require twin or pedigree data, which can be costly and difficult to acquire. Genome-wide complex trait analysis is an alternative tool to compute heritability estimates from unrelated individuals, using genome-wide data that are increasingly ubiquitous, but is computationally demanding and becomes difficult to apply in evaluating very large numbers of phenotypes. Here we present a fast and accurate statistical method for high-dimensional heritability analysis using genome-wide SNP data from unrelated individuals, termed massively expedited genome-wide heritability analysis (MEGHA) and accompanying nonparametric sampling techniques that enable flexible inferences for arbitrary statistics of interest. MEGHA produces estimates and significance measures of heritability with several orders of magnitude less computational time than existing methods, making heritability-based prioritization of millions of phenotypes based on data from unrelated individuals tractable for the first time to our knowledge. As a demonstration of application, we conducted heritability analyses on global and local morphometric measurements derived from brain structural MRI scans, using genome-wide SNP data from 1,320 unrelated young healthy adults of non-Hispanic European ancestry. We also computed surface maps of heritability for cortical thickness measures and empirically localized cortical regions where thickness measures were significantly heritable. Our analyses demonstrate the unique capability of MEGHA for large-scale heritability-based screening and high-dimensional heritability profile construction. PMID:25675487

  19. Massively expedited genome-wide heritability analysis (MEGHA)

    PubMed Central

    Ge, Tian; Nichols, Thomas E.; Lee, Phil H.; Holmes, Avram J.; Roffman, Joshua L.; Buckner, Randy L.; Sabuncu, Mert R.; Smoller, Jordan W.

    2015-01-01

    The discovery and prioritization of heritable phenotypes is a computational challenge in a variety of settings, including neuroimaging genetics and analyses of the vast phenotypic repositories in electronic health record systems and population-based biobanks. Classical estimates of heritability require twin or pedigree data, which can be costly and difficult to acquire. Genome-wide complex trait analysis is an alternative tool to compute heritability estimates from unrelated individuals, using genome-wide data that are increasingly ubiquitous, but is computationally demanding and becomes difficult to apply in evaluating very large numbers of phenotypes. Here we present a fast and accurate statistical method for high-dimensional heritability analysis using genome-wide SNP data from unrelated individuals, termed massively expedited genome-wide heritability analysis (MEGHA) and accompanying nonparametric sampling techniques that enable flexible inferences for arbitrary statistics of interest. MEGHA produces estimates and significance measures of heritability with several orders of magnitude less computational time than existing methods, making heritability-based prioritization of millions of phenotypes based on data from unrelated individuals tractable for the first time to our knowledge. As a demonstration of application, we conducted heritability analyses on global and local morphometric measurements derived from brain structural MRI scans, using genome-wide SNP data from 1,320 unrelated young healthy adults of non-Hispanic European ancestry. We also computed surface maps of heritability for cortical thickness measures and empirically localized cortical regions where thickness measures were significantly heritable. Our analyses demonstrate the unique capability of MEGHA for large-scale heritability-based screening and high-dimensional heritability profile construction. PMID:25675487

  20. Passive hip laxity in Estrela Mountain Dog--distraction index, heritability and breeding values.

    PubMed

    Ginja, Mário M D; Silvestre, António M; Ferreira, António J A; Gonzalo-Orden, José M; Orden, Maria A; Melo-Pinto, Pedro; Llorens-Pena, Maria P; Colaço, Jorge

    2008-09-01

    Two hundred and fifteen Estrela Mountain Dogs (EMD) were examined using the PennHIP method between 2002 and 2006. Passive hip laxity (PHL) was estimated calculating the distraction index (DI). Pedigree information was obtained from the Portuguese Kennel Club. The heritability and breeding values were estimated using the linear Animal Model. The DI, using as reference the worst joint of each animal, ranged from 0.15 to 1.12 (0.55 +/- 0.19). The PHL was equal in right and left sides, and was higher in females than in males (P > 0.05 and P <0.01 in the t-test, respectively). The estimated heritability was 0.83 +/- 0.11. The mean breeding values for PHL were stable in EMD born between 1991 and 2003, and showed an improvement in 2004 and 2005. The data confirm high PHL in breeds with high prevalence and severity of canine hip dysplasia. The high heritability indicates that the DI could be reduced in the breed if PHL were used as a selection criterion. The early favourable evolution of DI breeding values could be related with the increase of voluntary radiographic hip screening in the last years, and the subsequent introduction of hip quality as a breeding criterion. PMID:18828482

  1. Insights into the genetic history of Green-legged Partridgelike fowl: mtDNA and genome-wide SNP analysis

    PubMed Central

    Siwek, M; Wragg, D; Sławińska, A; Malek, M; Hanotte, O; Mwacharo, JM

    2013-01-01

    The Green-legged Partridgelike (GP) fowl, an old native Polish breed, is characterised by reseda green-coloured shanks rather than yellow, white, slate or black commonly observed across most domestic breeds of chicken. Here, we investigate the origin, genetic relationships and structure of the GP fowl using mtDNA D-loop sequencing and genome-wide SNP analysis. Genome-wide association analysis between breeds enables us to verify the genetic control of the reseda green shank phenotype, a defining trait for the breed. Two mtDNA D-loop haplogroups and three autosomal genetic backgrounds are revealed. Significant associations of SNPs on chromosomes GGA24 and GGAZ indicate that the reseda green leg phenotype is associated with recessive alleles linked to the W and Id loci. Our results provide new insights into the genetic history of European chicken, indicating an admixd origin of East European traditional breeds of chicken on the continent, as supported by the presence of the reseda green phenotype and the knowledge that the GP fowl as a breed was developed before the advent of commercial stocks. PMID:23611337

  2. Accuracy of predicting genomic breeding values for residual feed intake in Angus and Charolais beef cattle.

    PubMed

    Chen, L; Schenkel, F; Vinsky, M; Crews, D H; Li, C

    2013-10-01

    In beef cattle, phenotypic data that are difficult and/or costly to measure, such as feed efficiency, and DNA marker genotypes are usually available on a small number of animals of different breeds or populations. To achieve a maximal accuracy of genomic prediction using the phenotype and genotype data, strategies for forming a training population to predict genomic breeding values (GEBV) of the selection candidates need to be evaluated. In this study, we examined the accuracy of predicting GEBV for residual feed intake (RFI) based on 522 Angus and 395 Charolais steers genotyped on SNP with the Illumina Bovine SNP50 Beadchip for 3 training population forming strategies: within breed, across breed, and by pooling data from the 2 breeds (i.e., combined). Two other scenarios with the training and validation data split by birth year and by sire family within a breed were also investigated to assess the impact of genetic relationships on the accuracy of genomic prediction. Three statistical methods including the best linear unbiased prediction with the relationship matrix defined based on the pedigree (PBLUP), based on the SNP genotypes (GBLUP), and a Bayesian method (BayesB) were used to predict the GEBV. The results showed that the accuracy of the GEBV prediction was the highest when the prediction was within breed and when the validation population had greater genetic relationships with the training population, with a maximum of 0.58 for Angus and 0.64 for Charolais. The within-breed prediction accuracies dropped to 0.29 and 0.38, respectively, when the validation populations had a minimal pedigree link with the training population. When the training population of a different breed was used to predict the GEBV of the validation population, that is, across-breed genomic prediction, the accuracies were further reduced to 0.10 to 0.22, depending on the prediction method used. Pooling data from the 2 breeds to form the training population resulted in accuracies increased

  3. Acetaminophen-NAPQI Hepatotoxicity: A Cell Line Model System Genome-Wide Association Study

    PubMed Central

    Moyer, Ann M.; Fridley, Brooke L.; Jenkins, Gregory D.; Batzler, Anthony J.; Pelleymounter, Linda L.; Kalari, Krishna R.; Ji, Yuan; Chai, Yubo; Nordgren, Kendra K. S.; Weinshilboum, Richard M.

    2011-01-01

    Acetaminophen is the leading cause of acute hepatic failure in many developed nations. Acetaminophen hepatotoxicity is mediated by the reactive metabolite N-acetyl-p-benzoquinonimine (NAPQI). We performed a “discovery” genome-wide association study using a cell line–based model system to study the possible contribution of genomics to NAPQI-induced cytotoxicity. A total of 176 lymphoblastoid cell lines from healthy subjects were treated with increasing concentrations of NAPQI. Inhibiting concentration 50 values were determined and were associated with “glutathione pathway” gene single nucleotide polymorphisms (SNPs) and genome-wide basal messenger RNA expression, as well as with 1.3 million genome-wide SNPs. A group of SNPs in linkage disequilibrium on chromosome 3 was highly associated with NAPQI toxicity. The p value for rs2880961, the SNP with the lowest p value, was 1.88 × 10−7. This group of SNPs mapped to a “gene desert,” but chromatin immunoprecipitation assays demonstrated binding of several transcription factor proteins including heat shock factor 1 (HSF1) and HSF2, at or near rs2880961. These chromosome 3 SNPs were not significantly associated with variation in basal expression for any of the genome-wide genes represented on the Affymetrix U133 Plus 2.0 GeneChip. We have used a cell line–based model system to identify a SNP signal associated with NAPQI cytotoxicity. If these observations are validated in future clinical studies, this SNP signal might represent a potential biomarker for risk of acetaminophen hepatotoxicity. The mechanisms responsible for this association remain unclear. PMID:21177773

  4. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

    PubMed Central

    Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-01-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

  5. Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs.

    PubMed

    Wood, Shona Hiedi; Ke, Xiayi; Nuttall, Tim; McEwan, Neil; Ollier, William E; Carter, Stuart D

    2009-12-01

    In humans, genome-wide association studies (GWAS) have been shown to be an effective and thorough approach for identifying polymorphisms associated with disease phenotypes. Here, we describe the first study to perform a genome-wide association study in canine atopic dermatitis (cAD) using the Illumina Canine SNP20 array, containing 22,362 single-nucleotide polymorphisms (SNPs). The aim of the study was to identify SNPs associated with cAD using affected and unaffected Golden Retrievers. Further validation studies were performed for potentially associated SNPs using Sequenom genotyping of larger numbers of cases and controls across eight breeds (Boxer, German Shepherd Dog, Labrador, Golden Retriever, Shiba Inu, Shih Tzu, Pit Bull, and West Highland White Terriers). Using meta-analysis, two SNPs were associated with cAD in all breeds tested. RS22114085 was identified as a susceptibility locus (p=0.00014, odds ratio=2) and RS23472497 as a protective locus (p=0.0015, odds ratio=0.6). Both of these SNPs were located in intergenic regions, and their effects have been demonstrated to be independent of each other, highlighting that further fine mapping and resequencing is required of these areas. Further, 12 SNPs were validated by Sequenom genotyping as associated with cAD, but these were not associated with all breeds. This study suggests that GWAS will be a useful approach for identifying genetic risk factors for cAD. Given the clinical heterogeneity within this condition and the likelihood that the relative genetic effect sizes are small, greater sample sizes and further studies will be required. PMID:19838693

  6. Genome-wide patterns of selection in 230 ancient Eurasians

    PubMed Central

    Mathieson, Iain; Lazaridis, Iosif; Rohland, Nadin; Mallick, Swapan; Patterson, Nick; Roodenberg, Songül Alpaslan; Harney, Eadaoin; Stewardson, Kristin; Fernandes, Daniel; Novak, Mario; Sirak, Kendra; Gamba, Cristina; Jones, Eppie R.; Llamas, Bastien; Dryomov, Stanislav; Pickrel, Joseph; Arsuaga, Juan Luís; de Castro, José María Bermúdez; Carbonell, Eudald; Gerritsen, Fokke; Khokhlov, Aleksandr; Kuznetsov, Pavel; Lozano, Marina; Meller, Harald; Mochalov, Oleg; Moiseyev, Vayacheslav; Rojo Guerra, Manuel A.; Roodenberg, Jacob; Vergès, Josep Maria; Krause, Johannes; Cooper, Alan; Alt, Kurt W.; Brown, Dorcas; Anthony, David; Lalueza-Fox, Carles; Haak, Wolfgang; Pinhasi, Ron; Reich, David

    2016-01-01

    Ancient DNA makes it possible to directly witness natural selection by analyzing samples from populations before, during and after adaptation events. Here we report the first scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled: 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture whose genetic material we extracted from the DNA-rich petrous bone and who we show were members of the population that was the source of Europe’s first farmers. We also report a complete transect of the steppe region in Samara between 5500 and 1200 BCE that allows us to recognize admixture from at least two external sources into steppe populations during this period. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height. PMID:26595274

  7. Genome-wide patterns of selection in 230 ancient Eurasians.

    PubMed

    Mathieson, Iain; Lazaridis, Iosif; Rohland, Nadin; Mallick, Swapan; Patterson, Nick; Roodenberg, Songül Alpaslan; Harney, Eadaoin; Stewardson, Kristin; Fernandes, Daniel; Novak, Mario; Sirak, Kendra; Gamba, Cristina; Jones, Eppie R; Llamas, Bastien; Dryomov, Stanislav; Pickrell, Joseph; Arsuaga, Juan Luís; de Castro, José María Bermúdez; Carbonell, Eudald; Gerritsen, Fokke; Khokhlov, Aleksandr; Kuznetsov, Pavel; Lozano, Marina; Meller, Harald; Mochalov, Oleg; Moiseyev, Vyacheslav; Guerra, Manuel A Rojo; Roodenberg, Jacob; Vergès, Josep Maria; Krause, Johannes; Cooper, Alan; Alt, Kurt W; Brown, Dorcas; Anthony, David; Lalueza-Fox, Carles; Haak, Wolfgang; Pinhasi, Ron; Reich, David

    2015-12-24

    Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height. PMID:26595274

  8. Genome-Wide Significant Loci: How Important Are They?

    PubMed Central

    Björkegren, Johan L.M.; Kovacic, Jason C.; Dudley, Joel T.; Schadt, Eric E.

    2015-01-01

    Genome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key “drivers” of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities. PMID:25720628

  9. Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder

    PubMed Central

    Xie, Pingxing; Kranzler, Henry R.; Yang, Can; Zhao, Hongyu; Farrer, Lindsay A.; Gelernter, Joel

    2013-01-01

    Background Genetic factors influence the risk for posttraumatic stress disorder (PTSD), a potentially chronic and disabling psychiatric disorder that can arise after exposure to trauma. Candidate gene association studies have identified few genetic variants that contribute to PTSD risk. Methods We conducted genome-wide association analyses in 1578 European Americans (EAs), including 300 PTSD cases, and 2766 African Americans, including 444 PTSD cases, to find novel common risk alleles for PTSD. We used the Illumina Omni1-Quad microarray, which yielded approximately 870,000 single nucleotide polymorphisms (SNPs) suitable for analysis. Results In EAs, we observed that one SNP on chromosome 7p12, rs406001, exceeded genome-wide significance (p = 3.97×10−8). A SNP that maps to the first intron of the Tolloid-Like 1 gene (TLL1) showed the second strongest evidence of association, although no SNPs at this locus reached genome-wide significance. We then tested six SNPs in an independent sample of nearly 2000 EAs and successfully replicated the association findings for two SNPs in the first intron of TLL1, rs6812849 and rs7691872, with p values of 6.3×10−6 and 2.3×10−4, respectively. In the combined sample, rs6812849 had a p value of 3.1 ×10−9. No significant signals were observed in the African American part of the sample. Genome-wide association study analyses restricted to trauma-exposed individuals yielded very similar results. Conclusions This study identified TLL1 as a new susceptibility gene for PTSD. PMID:23726511

  10. A genome-wide scan for preeclampsia in the Netherlands.

    PubMed

    Lachmeijer, A M; Arngrímsson, R; Bastiaans, E J; Frigge, M L; Pals, G; Sigurdardóttir, S; Stéfansson, H; Pálsson, B; Nicolae, D; Kong, A; Aarnoudse, J G; Gulcher, J R; Dekker, G A; ten Kate, L P; Stéfansson, K

    2001-10-01

    Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New Zealand (NZ). The current study reports on a genome-wide scan of Dutch affected sib-pair families. In total 67 Dutch affected sib-pair families, comprising at least two siblings with proteinuric preeclampsia, eclampsia or HELLP-syndrome, were typed for 293 polymorphic markers throughout the genome and linkage analysis was performed. The highest allele sharing lod score of 1.99 was seen on chromosome 12q at 109.5 cM. Two peaks overlapped in the same regions between the Dutch and Icelandic genome-wide scan at chromosome 3p and chromosome 15q. No overlap was seen on 2p. Re-analysis in 38 families without HELLP-syndrome (preeclampsia families) and 34 families with at least one sibling with HELLP syndrome (HELLP families), revealed two peaks with suggestive evidence for linkage in the non-HELLP families on chromosome 10q (lod score 2.38, D10S1432, 93.9 cM) and 22q (lod score 2.41, D22S685, 32.4 cM). The peak on 12q appeared to be associated with HELLP syndrome; it increased to a lod score of 2.1 in the HELLP families and almost disappeared in the preeclampsia families. A nominal peak on chromosome 11 in the preeclampsia families showed overlap with the second highest peak in the Australian/NZ study. Results from our Dutch genome-wide scan indicate that HELLP syndrome might have a different genetic background than preeclampsia. PMID:11781687

  11. Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data

    PubMed Central

    Pickrell, Joseph K.; Pritchard, Jonathan K.

    2012-01-01

    Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and “ancient” Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com. PMID:23166502

  12. Genomic estimated breeding values using genomic relationship matrices in a cloned population of loblolly pine.

    PubMed

    Zapata-Valenzuela, Jaime; Whetten, Ross W; Neale, David; McKeand, Steve; Isik, Fikret

    2013-05-01

    Replacement of the average numerator relationship matrix derived from the pedigree with the realized genomic relationship matrix based on DNA markers might be an attractive strategy in forest tree breeding for predictions of genetic merit. We used genotypes from 3461 single-nucleotide polymorphism loci to estimate genomic relationships for a population of 165 loblolly pine (Pinus taeda L.) individuals. Phenotypes of the 165 individuals were obtained from clonally replicated field trials and were used to estimate breeding values for growth (stem volume). Two alternative methods, based on allele frequencies or regression, were used to generate the genomic relationship matrices. The accuracies of genomic estimated breeding values based on the genomic relationship matrices and breeding values estimated based on the average numerator relationship matrix were compared. On average, the accuracy of predictions based on genomic relationships ranged between 0.37 and 0.74 depending on the validation method. We did not detect differences in the accuracy of predictions based on genomic relationship matrices estimated by two different methods. Using genomic relationship matrices allowed modeling of Mendelian segregation within full-sib families, an important advantage over a traditional genetic evaluation system based on pedigree. We conclude that estimation of genomic relationships could be a powerful tool in forest tree breeding because it accurately accounts both for genetic relationships among individuals and for nuisance effects such as location and replicate effects, and makes more accurate selection possible within full-sib crosses. PMID:23585458

  13. Genome-Wide Detection and Analysis of Multifunctional Genes

    PubMed Central

    Pritykin, Yuri; Ghersi, Dario; Singh, Mona

    2015-01-01

    Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms—H. sapiens, D. melanogaster, and S. cerevisiae—and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

  14. Genome-Wide Detection and Analysis of Multifunctional Genes.

    PubMed

    Pritykin, Yuri; Ghersi, Dario; Singh, Mona

    2015-10-01

    Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

  15. Genome-wide association study of periodontal pathogen colonization.

    PubMed

    Divaris, K; Monda, K L; North, K E; Olshan, A F; Lange, E M; Moss, K; Barros, S P; Beck, J D; Offenbacher, S

    2012-07-01

    Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease. PMID:22699663

  16. Genome-wide polymorphisms show unexpected targets of natural selection.

    PubMed

    Pespeni, Melissa H; Garfield, David A; Manier, Mollie K; Palumbi, Stephen R

    2012-04-01

    Natural selection can act on all the expressed genes of an individual, leaving signatures of genetic differentiation or diversity at many loci across the genome. New power to assay these genome-wide effects of selection comes from associating multi-locus patterns of polymorphism with gene expression and function. Here, we performed one of the first genome-wide surveys in a marine species, comparing purple sea urchins, Strongylocentrotus purpuratus, from two distant locations along the species' wide latitudinal range. We examined 9112 polymorphic loci from upstream non-coding and coding regions of genes for signatures of selection with respect to gene function and tissue- and ontogenetic gene expression. We found that genetic differentiation (F(ST)) varied significantly across functional gene classes. The strongest enrichment occurred in the upstream regions of E3 ligase genes, enzymes known to regulate protein abundance during development and environmental stress. We found enrichment for high heterozygosity in genes directly involved in immune response, particularly NALP genes, which mediate pro-inflammatory signals during bacterial infection. We also found higher heterozygosity in immune genes in the southern population, where disease incidence and pathogen diversity are greater. Similar to the major histocompatibility complex in mammals, balancing selection may enhance genetic diversity in the innate immune system genes of this invertebrate. Overall, our results show that how genome-wide polymorphism data coupled with growing databases on gene function and expression can combine to detect otherwise hidden signals of selection in natural populations. PMID:21993504

  17. A Genome-Wide Association Study of Depressive Symptoms

    PubMed Central

    Cornelis, Marilyn C.; Amin, Najaf; Bakshis, Erin; Baumert, Jens; Ding, Jingzhong; Liu, Yongmei; Marciante, Kristin; Meirelles, Osorio; Nalls, Michael A.; Sun, Yan V.; Vogelzangs, Nicole; Yu, Lei; Bandinelli, Stefania; Benjamin, Emelia J.; Bennett, David A.; Boomsma, Dorret; Cannas, Alessandra; Coker, Laura H.; de Geus, Eco; De Jager, Philip L.; Diez-Roux, Ana V.; Purcell, Shaun; Hu, Frank B.; Rimma, Eric B.; Hunter, David J.; Jensen, Majken K.; Curhan, Gary; Rice, Kenneth; Penman, Alan D.; Rotter, Jerome I.; Sotoodehnia, Nona; Emeny, Rebecca; Eriksson, Johan G.; Evans, Denis A.; Ferrucci, Luigi; Fornage, Myriam; Gudnason, Vilmundur; Hofman, Albert; Illig, Thomas; Kardia, Sharon; Kelly-Hayes, Margaret; Koenen, Karestan; Kraft, Peter; Kuningas, Maris; Massaro, Joseph M.; Melzer, David; Mulas, Antonella; Mulder, Cornelis L.; Murray, Anna; Oostra, Ben A.; Palotie, Aarno; Penninx, Brenda; Petersmann, Astrid; Pilling, Luke C.; Psaty, Bruce; Rawal, Rajesh; Reiman, Eric M.; Schulz, Andrea; Shulman, Joshua M.; Singleton, Andrew B.; Smith, Albert V.; Sutin, Angelina R.; Uitterlinden, André G.; Völzke, Henry; Widen, Elisabeth; Yaffe, Kristine; Zonderman, Alan B.; Cucca, Francesco; Harris, Tamara; Ladwig, Karl-Heinz; Llewellyn, David J.; Räikkönen, Katri; Tanaka, Toshiko

    2013-01-01

    Background Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 × 10−5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 × 10−7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 × 10−3). This 5q21 region reached genome-wide significance (p = 4.78 × 10−8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. PMID:23290196

  18. Disruptive selection without genome-wide evolution across a migratory divide.

    PubMed

    von Rönn, Jan A C; Shafer, Aaron B A; Wolf, Jochen B W

    2016-06-01

    Transcontinental migration is a fascinating example of how animals can respond to climatic oscillation. Yet, quantitative data on fitness components are scarce, and the resulting population genetic consequences are poorly understood. Migratory divides, hybrid zones with a transition in migratory behaviour, provide a natural setting to investigate the micro-evolutionary dynamics induced by migration under sympatric conditions. Here, we studied the effects of migratory programme on survival, trait evolution and genome-wide patterns of population differentiation in a migratory divide of European barn swallows. We sampled a total of 824 individuals from both allopatric European populations wintering in central and southern Africa, respectively, along with two mixed populations from within the migratory divide. While most morphological characters varied by latitude consistent with Bergmann's rule, wing length co-varied with distance to wintering grounds. Survival data collected during a 5-year period provided strong evidence that this covariance is repeatedly generated by disruptive selection against intermediate phenotypes. Yet, selection-induced divergence did not translate into genome-wide genetic differentiation as assessed by microsatellites, mtDNA and >20 000 genome-wide SNP markers; nor did we find evidence of local genomic selection between migratory types. Among breeding populations, a single outlier locus mapped to the BUB1 gene with a role in mitotic and meiotic organization. Overall, this study provides evidence for an adaptive response to variation in migration behaviour continuously eroded by gene flow under current conditions of nonassortative mating. It supports the theoretical prediction that population differentiation is difficult to achieve under conditions of gene flow despite measurable disruptive selection. PMID:26749140

  19. A Comparison of Phenotypic Traits Related to Trypanotolerance in Five West African Cattle Breeds Highlights the Value of Shorthorn Taurine Breeds

    PubMed Central

    Berthier, David; Peylhard, Moana; Dayo, Guiguigbaza-Kossigan; Flori, Laurence; Sylla, Souleymane; Bolly, Seydou; Sakande, Hassane; Chantal, Isabelle; Thevenon, Sophie

    2015-01-01

    Background Animal African Trypanosomosis particularly affects cattle and dramatically impairs livestock development in sub-Saharan Africa. African Zebu (AFZ) or European taurine breeds usually die of the disease in the absence of treatment, whereas West African taurine breeds (AFT), considered trypanotolerant, are able to control the pathogenic effects of trypanosomosis. Up to now, only one AFT breed, the longhorn N’Dama (NDA), has been largely studied and is considered as the reference trypanotolerant breed. Shorthorn taurine trypanotolerance has never been properly assessed and compared to NDA and AFZ breeds. Methodology/Principal Findings This study compared the trypanotolerant/susceptible phenotype of five West African local breeds that differ in their demographic history. Thirty-six individuals belonging to the longhorn taurine NDA breed, two shorthorn taurine Lagune (LAG) and Baoulé (BAO) breeds, the Zebu Fulani (ZFU) and the Borgou (BOR), an admixed breed between AFT and AFZ, were infected by Trypanosoma congolense IL1180. All the cattle were genetically characterized using dense SNP markers, and parameters linked to parasitaemia, anaemia and leukocytes were analysed using synthetic variables and mixed models. We showed that LAG, followed by NDA and BAO, displayed the best control of anaemia. ZFU showed the greatest anaemia and the BOR breed had an intermediate value, as expected from its admixed origin. Large differences in leukocyte counts were also observed, with higher leukocytosis for AFT. Nevertheless, no differences in parasitaemia were found, except a tendency to take longer to display detectable parasites in ZFU. Conclusions We demonstrated that LAG and BAO are as trypanotolerant as NDA. This study highlights the value of shorthorn taurine breeds, which display strong local adaptation to trypanosomosis. Thanks to further analyses based on comparisons of the genome or transcriptome of the breeds, these results open up the way for better knowledge

  20. Genome-wide association discoveries of alcohol dependence

    PubMed Central

    Zuo, Lingjun; Lu, Lingeng; Tan, Yunlong; Pan, Xinghua; Cai, Yiqiang; Wang, Xiaoping; Hong, Jiang; Zhong, Chunlong; Wang, Fei; Zhang, Xiang-yang; Vanderlinden, Lauren A.; Tabakoff, Boris; Luo, Xingguang

    2014-01-01

    Objective To report the genome-wide significant and/or replicable risk variants for alcohol dependence and explore their potential biological functions. Methods We searched in PubMed for all genome-wide association studies (GWASs) of alcohol dependence. The following three types of the results were extracted: (1) genome-wide significant associations in an individual sample, the combined samples, or the meta-analysis (p<5×10−8); (2) top-ranked associations in an individual sample (p<10−5) that were nominally replicated in other samples (p<0.05); and (3) nominally replicable associations across at least three independent GWAS samples (p<0.05). These results were meta-analyzed. cis-eQTLs in human, RNA expression in rat and mouse brain and bioinformatics properties of all of these risk variants were analyzed. Results The variants located within ADH cluster were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in at least one sample. Some associations with the ADH cluster were replicable across six independent GWAS samples. The variants located within or near SERINC2, KIAA0040, MREG-PECR or PKNOX2 were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in meta-analysis or combined samples, and these associations were replicable across at least one sample. The associations with the variants within NRD1, GPD1L-CMTM8 or MAP3K9-PCNX were suggestive (5×10−8

  1. Genome Wide Association Mapping for Arabinoxylan Content in a Collection of Tetraploid Wheats

    PubMed Central

    Marcotuli, Ilaria; Houston, Kelly; Waugh, Robbie; Fincher, Geoffrey B.; Burton, Rachel A.; Blanco, Antonio; Gadaleta, Agata

    2015-01-01

    Background Arabinoxylans (AXs) are major components of plant cell walls in bread wheat and are important in bread-making and starch extraction. Furthermore, arabinoxylans are components of soluble dietary fibre that has potential health-promoting effects in human nutrition. Despite their high value for human health, few studies have been carried out on the genetics of AX content in durum wheat. Results The genetic variability of AX content was investigated in a set of 104 tetraploid wheat genotypes and regions attributable to AX content were identified through a genome wide association study (GWAS). The amount of arabinoxylan, expressed as percentage (w/w) of the dry weight of the kernel, ranged from 1.8% to 5.5% with a mean value of 4.0%. The GWAS revealed a total of 37 significant marker-trait associations (MTA), identifying 19 quantitative trait loci (QTL) associated with AX content. The highest number of MTAs was identified on chromosome 5A (seven), where three QTL regions were associated with AX content, while the lowest number of MTAs was detected on chromosomes 2B and 4B, where only one MTA identified a single locus. Conservation of synteny between SNP marker sequences and the annotated genes and proteins in Brachypodium distachyon, Oryza sativa and Sorghum bicolor allowed the identification of nine QTL coincident with candidate genes. These included a glycosyl hydrolase GH35, which encodes Gal7 and a glucosyltransferase GT31 on chromosome 1A; a cluster of GT1 genes on chromosome 2B that includes TaUGT1 and cisZog1; a glycosyl hydrolase that encodes a CelC gene on chromosome 3A; Ugt12887 and TaUGT1genes on chromosome 5A; a (1,3)-β-D-glucan synthase (Gsl12 gene) and a glucosyl hydrolase (Cel8 gene) on chromosome 7A. Conclusions This study identifies significant MTAs for the AX content in the grain of tetraploid wheat genotypes. We propose that these may be used for molecular breeding of durum wheat varieties with higher soluble fibre content. PMID:26176552

  2. Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.

    PubMed

    Adkins, Daniel E; Clark, Shaunna L; Copeland, William E; Kennedy, Martin; Conway, Kevin; Angold, Adrian; Maes, Hermine; Liu, Youfang; Kumar, Gaurav; Erkanli, Alaattin; Patkar, Ashwin A; Silberg, Judy; Brown, Tyson H; Fergusson, David M; Horwood, L John; Eaves, Lindon; van den Oord, Edwin J C G; Sullivan, Patrick F; Costello, E J

    2015-08-01

    The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N=2,126, obs=12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and six others met our 'suggestive' criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies. PMID:26081443

  3. Genome-wide meta-analysis of longitudinal alcohol consumption across youth and early adulthood

    PubMed Central

    Adkins, Daniel E.; Clark, Shaunna L.; Copeland, William E.; Kennedy, Martin; Conway, Kevin; Angold, Adrian; Maes, Hermine; Liu, Youfang; Kumar, Gaurav; Erkanli, Alaattin; Patkar, Ashwin A.; Silberg, Judy; Brown, Tyson H.; Fergusson, David M.; Horwood, L. John; Eaves, Lindon; van den Oord, Edwin J.C.G.; Sullivan, Patrick F.; Costello, E. J.

    2016-01-01

    The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse and dependence increasing across adolescence and peaking in early adulthood. Here we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three, longitudinal community samples (N=2,126, obs=12,166). Consumption repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and 6 others met our “suggestive” criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms including neurotransmission, xenobiotic pharmacodynamics and nuclear hormone receptors. These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies. PMID:26081443

  4. Simulation of genome-wide evolution under heterogeneous substitution models and complex multispecies coalescent histories.

    PubMed

    Arenas, Miguel; Posada, David

    2014-05-01

    Genomic evolution can be highly heterogeneous. Here, we introduce a new framework to simulate genome-wide sequence evolution under a variety of substitution models that may change along the genome and the phylogeny, following complex multispecies coalescent histories that can include recombination, demographics, longitudinal sampling, population subdivision/species history, and migration. A key aspect of our simulation strategy is that the heterogeneity of the whole evolutionary process can be parameterized according to statistical prior distributions specified by the user. We used this framework to carry out a study of the impact of variable codon frequencies across genomic regions on the estimation of the genome-wide nonsynonymous/synonymous ratio. We found that both variable codon frequencies across genes and rate variation among sites and regions can lead to severe underestimation of the global dN/dS values. The program SGWE-Simulation of Genome-Wide Evolution-is freely available from http://code.google.com/p/sgwe-project/, including extensive documentation and detailed examples. PMID:24557445

  5. Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study.

    PubMed

    Koga, Arthur T; Strauss, John; Zai, Clement; Remington, Gary; De Luca, Vincenzo

    2016-03-01

    In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication. PMID:26821981

  6. Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis.

    PubMed

    Phipps, Amanda I; Passarelli, Michael N; Chan, Andrew T; Harrison, Tabitha A; Jeon, Jihyoun; Hutter, Carolyn M; Berndt, Sonja I; Brenner, Hermann; Caan, Bette J; Campbell, Peter T; Chang-Claude, Jenny; Chanock, Stephen J; Cheadle, Jeremy P; Curtis, Keith R; Duggan, David; Fisher, David; Fuchs, Charles S; Gala, Manish; Giovannucci, Edward L; Hayes, Richard B; Hoffmeister, Michael; Hsu, Li; Jacobs, Eric J; Jansen, Lina; Kaplan, Richard; Kap, Elisabeth J; Maughan, Timothy S; Potter, John D; Schoen, Robert E; Seminara, Daniela; Slattery, Martha L; West, Hannah; White, Emily; Peters, Ulrike; Newcomb, Polly A

    2016-01-01

    Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival outcomes after CRC diagnosis. Genome-wide genotyping arrays were conducted for 3494 individuals with invasive CRC enrolled in six prospective cohort studies (median study-specific follow-up = 4.2-8.1 years). In pooled analyses, we used Cox regression to assess SNP-specific associations with CRC-specific and overall survival, with additional analyses stratified by stage at diagnosis. Top findings were followed-up in independent studies. A P value threshold of P < 5×10(-8) in analyses combining discovery and follow-up studies was required for genome-wide significance. Among individuals with distant-metastatic CRC, several SNPs at 6p12.1, nearest the ELOVL5 gene, were statistically significantly associated with poorer survival, with the strongest associations noted for rs209489 [hazard ratio (HR) = 1.8, P = 7.6×10(-10) and HR = 1.8, P = 3.7×10(-9) for CRC-specific and overall survival, respectively). No SNPs were statistically significantly associated with survival among all cases combined or in cases without distant-metastases. SNPs in 6p12.1/ELOVL5 were associated with survival outcomes in individuals with distant-metastatic CRC, and merit further follow-up for functional significance. Findings from this genome-wide association study highlight the potential importance of genetic variation in CRC prognosis and provide clues to genomic regions of potential interest. PMID:26586795

  7. Genome-wide association studies for multiple diseases of the German Shepherd Dog.

    PubMed

    Tsai, Kate L; Noorai, Rooksana E; Starr-Moss, Alison N; Quignon, Pascale; Rinz, Caitlin J; Ostrander, Elaine A; Steiner, Jörg M; Murphy, Keith E; Clark, Leigh Anne

    2012-02-01

    The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder. PMID:22105877

  8. Genome-wide association studies for fatty acid metabolic traits in five divergent pig populations

    PubMed Central

    Zhang, Wanchang; Bin Yang; Zhang, Junjie; Cui, Leilei; Ma, Junwu; Chen, Congying; Ai, Huashui; Xiao, Shijun; Ren, Jun; Huang, Lusheng

    2016-01-01

    Fatty acid composition profiles are important indicators of meat quality and tasting flavor. Metabolic indices of fatty acids are more authentic to reflect meat nutrition and public acceptance. To investigate the genetic mechanism of fatty acid metabolic indices in pork, we conducted genome-wide association studies (GWAS) for 33 fatty acid metabolic traits in five pig populations. We identified a total of 865 single nucleotide polymorphisms (SNPs), corresponding to 11 genome-wide significant loci on nine chromosomes and 12 suggestive loci on nine chromosomes. Our findings not only confirmed seven previously reported QTL with stronger association strength, but also revealed four novel population-specific loci, showing that investigations on intermediate phenotypes like the metabolic traits of fatty acids can increase the statistical power of GWAS for end-point phenotypes. We proposed a list of candidate genes at the identified loci, including three novel genes (FADS2, SREBF1 and PLA2G7). Further, we constructed the functional networks involving these candidate genes and deduced the potential fatty acid metabolic pathway. These findings advance our understanding of the genetic basis of fatty acid composition in pigs. The results from European hybrid commercial pigs can be immediately transited into breeding practice for beneficial fatty acid composition. PMID:27097669

  9. Genome-wide association study of drought-related resistance traits in Aegilops tauschii

    PubMed Central

    Qin, Peng; Lin, Yu; Hu, Yaodong; Liu, Kun; Mao, Shuangshuang; Li, Zhanyi; Wang, Jirui; Liu, Yaxi; Wei, Yuming; Zheng, Youliang

    2016-01-01

    Abstract The D-genome progenitor of wheat (Triticum aestivum), Aegilops tauschii, possesses numerous genes for resistance to abiotic stresses, including drought. Therefore, information on the genetic architecture of A. tauschii can aid the development of drought-resistant wheat varieties. Here, we evaluated 13 traits in 373 A. tauschii accessions grown under normal and polyethylene glycol-simulated drought stress conditions and performed a genome-wide association study using 7,185 single nucleotide polymorphism (SNP) markers. We identified 208 and 28 SNPs associated with all traits using the general linear model and mixed linear model, respectively, while both models detected 25 significant SNPs with genome-wide distribution. Public database searches revealed several candidate/flanking genes related to drought resistance that were grouped into three categories according to the type of encoded protein (enzyme, storage protein, and drought-induced protein). This study provided essential information for SNPs and genes related to drought resistance in A. tauschii and wheat, and represents a foundation for breeding drought-resistant wheat cultivars using marker-assisted selection. PMID:27560650

  10. Development and application of a novel genome-wide SNP array reveals domestication history in soybean

    PubMed Central

    Wang, Jiao; Chu, Shanshan; Zhang, Huairen; Zhu, Ying; Cheng, Hao; Yu, Deyue

    2016-01-01

    Domestication of soybeans occurred under the intense human-directed selections aimed at developing high-yielding lines. Tracing the domestication history and identifying the genes underlying soybean domestication require further exploration. Here, we developed a high-throughput NJAU 355 K SoySNP array and used this array to study the genetic variation patterns in 367 soybean accessions, including 105 wild soybeans and 262 cultivated soybeans. The population genetic analysis suggests that cultivated soybeans have tended to originate from northern and central China, from where they spread to other regions, accompanied with a gradual increase in seed weight. Genome-wide scanning for evidence of artificial selection revealed signs of selective sweeps involving genes controlling domestication-related agronomic traits including seed weight. To further identify genomic regions related to seed weight, a genome-wide association study (GWAS) was conducted across multiple environments in wild and cultivated soybeans. As a result, a strong linkage disequilibrium region on chromosome 20 was found to be significantly correlated with seed weight in cultivated soybeans. Collectively, these findings should provide an important basis for genomic-enabled breeding and advance the study of functional genomics in soybean. PMID:26856884

  11. Genome-wide association study of drought-related resistance traits in Aegilops tauschii.

    PubMed

    Qin, Peng; Lin, Yu; Hu, Yaodong; Liu, Kun; Mao, Shuangshuang; Li, Zhanyi; Wang, Jirui; Liu, Yaxi; Wei, Yuming; Zheng, Youliang

    2016-07-01

    The D-genome progenitor of wheat (Triticum aestivum), Aegilops tauschii, possesses numerous genes for resistance to abiotic stresses, including drought. Therefore, information on the genetic architecture of A. tauschii can aid the development of drought-resistant wheat varieties. Here, we evaluated 13 traits in 373 A. tauschii accessions grown under normal and polyethylene glycol-simulated drought stress conditions and performed a genome-wide association study using 7,185 single nucleotide polymorphism (SNP) markers. We identified 208 and 28 SNPs associated with all traits using the general linear model and mixed linear model, respectively, while both models detected 25 significant SNPs with genome-wide distribution. Public database searches revealed several candidate/flanking genes related to drought resistance that were grouped into three categories according to the type of encoded protein (enzyme, storage protein, and drought-induced protein). This study provided essential information for SNPs and genes related to drought resistance in A. tauschii and wheat, and represents a foundation for breeding drought-resistant wheat cultivars using marker-assisted selection. PMID:27392238

  12. Genome-Wide Divergence in the West-African Malaria Vector Anopheles melas.

    PubMed

    Deitz, Kevin C; Athrey, Giridhar A; Jawara, Musa; Overgaard, Hans J; Matias, Abrahan; Slotman, Michel A

    2016-01-01

    Anopheles melas is a member of the recently diverged An. gambiae species complex, a model for speciation studies, and is a locally important malaria vector along the West-African coast where it breeds in brackish water. A recent population genetic study of An. melas revealed species-level genetic differentiation between three population clusters. An. melas West extends from The Gambia to the village of Tiko, Cameroon. The other mainland cluster, An. melas South, extends from the southern Cameroonian village of Ipono to Angola. Bioko Island, Equatorial Guinea An. melas populations are genetically isolated from mainland populations. To examine how genetic differentiation between these An. melas forms is distributed across their genomes, we conducted a genome-wide analysis of genetic differentiation and selection using whole genome sequencing data of pooled individuals (Pool-seq) from a representative population of each cluster. The An. melas forms exhibit high levels of genetic differentiation throughout their genomes, including the presence of numerous fixed differences between clusters. Although the level of divergence between the clusters is on a par with that of other species within the An. gambiae complex, patterns of genome-wide divergence and diversity do not provide evidence for the presence of pre- and/or postmating isolating mechanisms in the form of speciation islands. These results are consistent with an allopatric divergence process with little or no introgression. PMID:27466271

  13. Genome-wide association study of drought-related resistance traits in Aegilops tauschii.

    PubMed

    Qin, Peng; Lin, Yu; Hu, Yaodong; Liu, Kun; Mao, Shuangshuang; Li, Zhanyi; Wang, Jirui; Liu, Yaxi; Wei, Yuming; Zheng, Youliang

    2016-01-01

    The D-genome progenitor of wheat (Triticum aestivum), Aegilops tauschii, possesses numerous genes for resistance to abiotic stresses, including drought. Therefore, information on the genetic architecture of A. tauschii can aid the development of drought-resistant wheat varieties. Here, we evaluated 13 traits in 373 A. tauschii accessions grown under normal and polyethylene glycol-simulated drought stress conditions and performed a genome-wide association study using 7,185 single nucleotide polymorphism (SNP) markers. We identified 208 and 28 SNPs associated with all traits using the general linear model and mixed linear model, respectively, while both models detected 25 significant SNPs with genome-wide distribution. Public database searches revealed several candidate/flanking genes related to drought resistance that were grouped into three categories according to the type of encoded protein (enzyme, storage protein, and drought-induced protein). This study provided essential information for SNPs and genes related to drought resistance in A. tauschii and wheat, and represents a foundation for breeding drought-resistant wheat cultivars using marker-assisted selection. PMID:27560650

  14. Genome-Wide Divergence in the West-African Malaria Vector Anopheles melas

    PubMed Central

    Deitz, Kevin C.; Athrey, Giridhar A.; Jawara, Musa; Overgaard, Hans J.; Matias, Abrahan; Slotman, Michel A.

    2016-01-01

    Anopheles melas is a member of the recently diverged An. gambiae species complex, a model for speciation studies, and is a locally important malaria vector along the West-African coast where it breeds in brackish water. A recent population genetic study of An. melas revealed species-level genetic differentiation between three population clusters. An. melas West extends from The Gambia to the village of Tiko, Cameroon. The other mainland cluster, An. melas South, extends from the southern Cameroonian village of Ipono to Angola. Bioko Island, Equatorial Guinea An. melas populations are genetically isolated from mainland populations. To examine how genetic differentiation between these An. melas forms is distributed across their genomes, we conducted a genome-wide analysis of genetic differentiation and selection using whole genome sequencing data of pooled individuals (Pool-seq) from a representative population of each cluster. The An. melas forms exhibit high levels of genetic differentiation throughout their genomes, including the presence of numerous fixed differences between clusters. Although the level of divergence between the clusters is on a par with that of other species within the An. gambiae complex, patterns of genome-wide divergence and diversity do not provide evidence for the presence of pre- and/or postmating isolating mechanisms in the form of speciation islands. These results are consistent with an allopatric divergence process with little or no introgression. PMID:27466271

  15. Genome-wide association studies for fatty acid metabolic traits in five divergent pig populations.

    PubMed

    Zhang, Wanchang; Bin Yang; Zhang, Junjie; Cui, Leilei; Ma, Junwu; Chen, Congying; Ai, Huashui; Xiao, Shijun; Ren, Jun; Huang, Lusheng

    2016-01-01

    Fatty acid composition profiles are important indicators of meat quality and tasting flavor. Metabolic indices of fatty acids are more authentic to reflect meat nutrition and public acceptance. To investigate the genetic mechanism of fatty acid metabolic indices in pork, we conducted genome-wide association studies (GWAS) for 33 fatty acid metabolic traits in five pig populations. We identified a total of 865 single nucleotide polymorphisms (SNPs), corresponding to 11 genome-wide significant loci on nine chromosomes and 12 suggestive loci on nine chromosomes. Our findings not only confirmed seven previously reported QTL with stronger association strength, but also revealed four novel population-specific loci, showing that investigations on intermediate phenotypes like the metabolic traits of fatty acids can increase the statistical power of GWAS for end-point phenotypes. We proposed a list of candidate genes at the identified loci, including three novel genes (FADS2, SREBF1 and PLA2G7). Further, we constructed the functional networks involving these candidate genes and deduced the potential fatty acid metabolic pathway. These findings advance our understanding of the genetic basis of fatty acid composition in pigs. The results from European hybrid commercial pigs can be immediately transited into breeding practice for beneficial fatty acid composition. PMID:27097669

  16. Development and application of a novel genome-wide SNP array reveals domestication history in soybean.

    PubMed

    Wang, Jiao; Chu, Shanshan; Zhang, Huairen; Zhu, Ying; Cheng, Hao; Yu, Deyue

    2016-01-01

    Domestication of soybeans occurred under the intense human-directed selections aimed at developing high-yielding lines. Tracing the domestication history and identifying the genes underlying soybean domestication require further exploration. Here, we developed a high-throughput NJAU 355 K SoySNP array and used this array to study the genetic variation patterns in 367 soybean accessions, including 105 wild soybeans and 262 cultivated soybeans. The population genetic analysis suggests that cultivated soybeans have tended to originate from northern and central China, from where they spread to other regions, accompanied with a gradual increase in seed weight. Genome-wide scanning for evidence of artificial selection revealed signs of selective sweeps involving genes controlling domestication-related agronomic traits including seed weight. To further identify genomic regions related to seed weight, a genome-wide association study (GWAS) was conducted across multiple environments in wild and cultivated soybeans. As a result, a strong linkage disequilibrium region on chromosome 20 was found to be significantly correlated with seed weight in cultivated soybeans. Collectively, these findings should provide an important basis for genomic-enabled breeding and advance the study of functional genomics in soybean. PMID:26856884

  17. EVALUATION OF GENETIC DIVERSITY AND GENOME-WIDE LINKAGE DISEQUILIBRIUM AMOUNG US WHEAT (TRITICUM AETIVUM L.) GERMPLASM REPRESENTING DIFFERENT MARKET CLASSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic diversity and genome-wide linkage disequilibrium (LD) were investigated among forty-three US wheat (Triticum aestivum L.) elite cultivars and breeding lines representing seven US wheat market classes using 242 wheat genomic simple sequence repeat (SSR) markers distributed throughout the whea...

  18. Genome-wide association study reveals novel variants for growth and egg traits in Dongxiang blue-shelled and White Leghorn chickens.

    PubMed

    Liao, R; Zhang, X; Chen, Q; Wang, Z; Wang, Q; Yang, C; Pan, Y

    2016-10-01

    This study was designed to investigate the genetic basis of growth and egg traits in Dongxiang blue-shelled chickens and White Leghorn chickens. In this study, we employed a reduced representation sequencing approach called genotyping by genome reducing and sequencing to detect genome-wide SNPs in 252 Dongxiang blue-shelled chickens and 252 White Leghorn chickens. The Dongxiang blue-shelled chicken breed has many specific traits and is characterized by blue-shelled eggs, black plumage, black skin, black bone and black organs. The White Leghorn chicken is an egg-type breed with high productivity. As multibreed genome-wide association studies (GWASs) can improve precision due to less linkage disequilibrium across breeds, a multibreed GWAS was performed with 156 575 SNPs to identify the associated variants underlying growth and egg traits within the two chicken breeds. The analysis revealed 32 SNPs exhibiting a significant genome-wide association with growth and egg traits. Some of the significant SNPs are located in genes that are known to impact growth and egg traits, but nearly half of the significant SNPs are located in genes with unclear functions in chickens. To our knowledge, this is the first multibreed genome-wide report for the genetics of growth and egg traits in the Dongxiang blue-shelled and White Leghorn chickens. PMID:27166871

  19. Evaluation of genetic diversity and genome-wide linkage disequilibrium among US wheat (Triticum aestivum L.) germplasm representing different market classes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic diversity and genome-wide linkage disequilibrium (LD) were investigated among forty-three U.S. wheat (Triticum aestivum L.) elite cultivars and breeding lines representing seven U.S. wheat market classes using 242 wheat genomic simple sequence repeat (SSR) markers distributed throughout the ...

  20. Comparison of Bayesian models to estimate direct genomic values in multi-breed commercial beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Several studies have examined the accuracy of genomic selection both within and across purebred beef or dairy populations. However, the accuracy of direct genomic breeding values (DGVs) has been less well studied in crossbred or admixed cattle populations. We used a population of 3,240 cr...

  1. Genetic Correlations Between Carcass Traits And Molecular Breeding Values In Angus Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research elucidated genetic relationships between carcass traits, ultrasound indicator traits, and their respective molecular breeding values (MBV). Animals whose MBV data were used to estimate (co)variance components were not previously used in development of the MBV. Results are presented fo...

  2. Phenotypic structures and breeding value of open-pollinated corn varietal hybrids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The growing interest in using open-pollinated varieties (OPVs) and varietal hybrids (OPVhs) of corn (Zea mays L.) especially in breeding programs for organic and low-input farming reflects the value of large plasticity levels available in their plant, ear, and kernel traits. We estimated and partiti...

  3. Genome-wide linkage and association analysis identifies major gene loci for guttural pouch tympany in Arabian and German warmblood horses.

    PubMed

    Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

    2012-01-01

    Equine guttural pouch tympany (GPT) is a hereditary condition affecting foals in their first months of life. Complex segregation analyses in Arabian and German warmblood horses showed the involvement of a major gene as very likely. Genome-wide linkage and association analyses including a high density marker set of single nucleotide polymorphisms (SNPs) were performed to map the genomic region harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non-parametric multipoint linkage analyses showed genome-wide significance on horse chromosomes (ECA) 3 for German warmblood at 16-26 Mb and 34-55 Mb and for Arabian on ECA15 at 64-65 Mb. Genome-wide association analyses confirmed the linked regions for both breeds. In Arabian, genome-wide association was detected at 64 Mb within the region with the highest linkage peak on ECA15. For German warmblood, signals for genome-wide association were close to the peak region of linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide association was 0.12 for the Arabian. In conclusion, the refinement of the regions with the Illumina equine SNP50 beadchip is an important step to unravel the responsible mutations for GPT. PMID:22848553

  4. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    PubMed Central

    2012-01-01

    Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association study identified several

  5. Genome-wide Association Study Identifies Loci for the Polled Phenotype in Yak

    PubMed Central

    Wu, Xiaoyun; Wang, Kun; Ding, Xuezhi; Wang, Mingcheng; Chu, Min; Xie, Xiuyue; Qiu, Qiang; Yan, Ping

    2016-01-01

    The absence of horns, known as the polled phenotype, is an economically important trait in modern yak husbandry, but the genomic structure and genetic basis of this phenotype have yet to be discovered. Here, we conducted a genome-wide association study with a panel of 10 horned and 10 polled yaks using whole genome sequencing. We mapped the POLLED locus to a 200-kb interval, which comprises three protein-coding genes. Further characterization of the candidate region showed recent artificial selection signals resulting from the breeding process. We suggest that expressional variations rather than structural variations in protein probably contribute to the polled phenotype. Our results not only represent the first and important step in establishing the genomic structure of the polled region in yak, but also add to our understanding of the polled trait in bovid species. PMID:27389700

  6. Genome-Wide Association Mapping for Tomato Volatiles Positively Contributing to Tomato Flavor

    PubMed Central

    Zhang, Jing; Zhao, Jiantao; Xu, Yao; Liang, Jing; Chang, Peipei; Yan, Fei; Li, Mingjun; Liang, Yan; Zou, Zhirong

    2015-01-01

    Tomato volatiles, mainly derived from essential nutrients and health-promoting precursors, affect tomato flavor. Taste volatiles present a major challenge for flavor improvement and quality breeding. In this study, we performed genome-wide association studies (GWAS) to investigate potential chromosome regions associated with the tomato flavor volatiles. We observed significant variation (1200x) among the selected 28 most important volatiles in tomato based on their concentration and odor threshold importance across our sampled accessions. Using 174 tomato accessions, GWAS identified 125 significant associations (P < 0.005) among 182 SSR markers and 28 volatiles (27 volatiles with at least one significant association). Several significant associations were co-localized in previously identified quantitative trait loci (QTL). This result provides new potential candidate loci affecting the metabolism of several volatiles. PMID:26640472

  7. Exploring genome wide bisulfite sequencing for DNA methylation analysis in livestock: a technical assessment.

    PubMed

    Doherty, Rachael; Couldrey, Christine

    2014-01-01

    Recent advances made in "omics" technologies are contributing to a revolution in livestock selection and breeding practices. Epigenetic mechanisms, including DNA methylation are important determinants for the control of gene expression in mammals. DNA methylation research will help our understanding of how environmental factors contribute to phenotypic variation of complex production and health traits. High-throughput sequencing is a vital tool for the comprehensive analysis of DNA methylation, and bisulfite-based strategies coupled with DNA sequencing allows for quantitative, site-specific methylation analysis at the genome level or genome wide. Reduced representation bisulfite sequencing (RRBS) and more recently whole genome bisulfite sequencing (WGBS) have proven to be effective techniques for studying DNA methylation in both humans and mice. Here we report the development of RRBS and WGBS for use in sheep, the first application of this technology in livestock species. Important technical issues associated with these methodologies including fragment size selection and sequence depth are examined and discussed. PMID:24860595

  8. Genome-wide Association Study Identifies Loci for the Polled Phenotype in Yak.

    PubMed

    Liang, Chunnian; Wang, Lizhong; Wu, Xiaoyun; Wang, Kun; Ding, Xuezhi; Wang, Mingcheng; Chu, Min; Xie, Xiuyue; Qiu, Qiang; Yan, Ping

    2016-01-01

    The absence of horns, known as the polled phenotype, is an economically important trait in modern yak husbandry, but the genomic structure and genetic basis of this phenotype have yet to be discovered. Here, we conducted a genome-wide association study with a panel of 10 horned and 10 polled yaks using whole genome sequencing. We mapped the POLLED locus to a 200-kb interval, which comprises three protein-coding genes. Further characterization of the candidate region showed recent artificial selection signals resulting from the breeding process. We suggest that expressional variations rather than structural variations in protein probably contribute to the polled phenotype. Our results not only represent the first and important step in establishing the genomic structure of the polled region in yak, but also add to our understanding of the polled trait in bovid species. PMID:27389700

  9. Genome-Wide Approaches to Drosophila Heart Development

    PubMed Central

    Frasch, Manfred

    2016-01-01

    The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control Drosophila cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated Drosophila genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi) reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to Drosophila heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level. PMID:27294102

  10. Voxelwise genome-wide association study (vGWAS)

    PubMed Central

    Stein, Jason L.; Hua, Xue; Lee, Suh; Ho, April J.; Leow, Alex D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; DeChairo, Bryan M.; Potkin, Steven G.; Weiner, Michael W.; Thompson, Paul M.

    2010-01-01

    The structure of the human brain is highly heritable, and is thought to be influenced by many common genetic variants, many of which are currently unknown. Recent advances in neuroimaging and genetics have allowed collection of both highly detailed structural brain scans and genome-wide genotype information. This wealth of information presents a new opportunity to find the genes influencing brain structure. Here we explore the relation between 448,293 single nucleotide polymorphisms in each of 31,622 voxels of the entire brain across 740 elderly subjects (mean age±s.d.: 75.52±6.82 years; 438 male) including subjects with Alzheimer's disease, Mild Cognitive Impairment, and healthy elderly controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used tensor-based morphometry to measure individual differences in brain structure at the voxel level relative to a study-specific template based on healthy elderly subjects. We then conducted a genome-wide association at each voxel to identify genetic variants of interest. By studying only the most associated variant at each voxel, we developed a novel method to address the multiple comparisons problem and computational burden associated with the unprecedented amount of data. No variant survived the strict significance criterion, but several genes worthy of further exploration were identified, including CSMD2 and CADPS2. These genes have high relevance to brain structure. This is the first voxelwise genome wide association study to our knowledge, and offers a novel method to discover genetic influences on brain structure. PMID:20171287

  11. Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes

    PubMed Central

    Taylor, Sarah E. B.; Li, Ye Henry; Wong, Wing H.; Bhutani, Nidhi

    2015-01-01

    Objective To examine genome-wide 5hmC distribution in osteoarthritic (OA) and normal chondrocytes to investigate the effect on OA-specific gene expression. Methods Cartilage was obtained from OA patients undergoing total knee arthroplasty or control patients undergoing anterior cruciate ligament reconstruction. Genome-wide sequencing of 5hmC-enriched DNA (5hmC-seq) was performed for a small cohort of normal and OA chondrocytes to identify differentially hydroxymethylated regions (DhMRs) in OA chondrocytes. 5hmC-seq data was intersected with global OA gene expression data to define subsets of genes and pathways potentially affected by increased 5hmC levels in OA chondrocytes. Results 70591 DhMRs were identified in OA chondrocytes compared to normal chondrocytes, 44288 (63%) of which were increased in OA chondrocytes. The majority of DhMRs (66%) were gained in gene bodies. Increased DhMRs were observed in ~50% of genes previously implicated in OA pathology including MMP3, LRP5, GDF5 and COL11A1. Furthermore, analyses of gene expression data revealed gene body gain of 5hmC appears to be preferentially associated with activated but not repressed genes in OA chondrocytes. Conclusion This study provides the first genome-wide profiling of 5hmC distribution in OA chondrocytes. We had previously reported a global increase in 5hmC levels in OA chondrocytes. Gain of 5hmC in the gene body is found to be characteristic of activated genes in OA chondrocytes, highlighting the influence of 5hmC as an epigenetic mark in OA. In addition, this study identifies multiple OA-associated genes that are potentially regulated either singularly by gain of DNA hydroxymethylation or in combination with loss of DNA methylation. PMID:25940674

  12. [Genome-wide association study for adolescent idiopathic scoliosis].

    PubMed

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS. PMID:27013625

  13. Genome-wide profiling of alternative splicing in Alzheimer's disease

    PubMed Central

    Lai, Mitchell K.P.; Esiri, Margaret M.; Tan, Michelle G.K.

    2014-01-01

    Alternative splicing is a highly regulated process which generates transcriptome and proteome diversity through the skipping or inclusion of exons within gene loci. Identification of aberrant alternative splicing associated with human diseases has become feasible with the development of new genomic technologies and powerful bioinformatics. We have previously reported genome-wide gene alterations in the neocortex of a well-characterized cohort of Alzheimer's disease (AD) patients and matched elderly controls using a commercial exon microarray platform [1]. Here, we provide detailed description of analyses aimed at identifying differential alternative splicing events associated with AD. PMID:26484111

  14. [New insight of genome-wide association study (GWAS)].

    PubMed

    Hotta, Kikuko

    2013-02-01

    The number of obese patients is increasing in Japan, due to the westernization of lifestyle. Obesity, especially visceral fat obesity, is important for the development of metabolic syndrome. Genetic factors are important for the development of obesity as well as environmental factors. Importance of genetic factors of fat distribution is also reported. Recent genome-wide association studies (GWASs) have revealed the obesity and fat distribution-related polymorphisms. GWAS will highlight a better understanding of the underlying molecular mechanisms in the regulation of obesity and distribution of body fat. PMID:23631198

  15. Genome-wide association studies in diverse populations

    PubMed Central

    Rosenberg, Noah A; Huang, Lucy; Jewett, Ethan M; Szpiech, Zachary A; Jankovic, Ivana; Boehnke, Michael

    2011-01-01

    Genome-wide association (GWA) studies have identified a large number of single-nucleotide polymorphisms (SNPs) associated with disease phenotypes. As most GWA studies have been performed primarily in populations of European descent, this review examines the issues involved in extending consideration of GWA studies to diverse worldwide populations. Although challenges exist with such issues as imputation, admixture, and replication, investigation of diverse populations in GWA studies has significant potential to advance the project of mapping the genetic determinants of complex diseases for the human population as a whole. PMID:20395969

  16. Genome-Wide Association Studies for Polycystic Ovary Syndrome.

    PubMed

    Liu, Hongbin; Zhao, Han; Chen, Zi-Jiang

    2016-07-01

    Over the past several years, the field of reproductive medicine has witnessed great advances in genome-wide association studies (GWASs) of polycystic ovary syndrome (PCOS), leading to identification of several promising genes involved in hormone action, type 2 diabetes, and cell proliferation. This review summarizes the key findings and discusses their potential implications with regard to genetic mechanisms of PCOS. Limitations of GWAS are evaluated, emphasizing the understanding of the reasons for variability in results between individual studies. Root causes of misinterpretations of GWASs are also addressed. Finally, the impact of GWAS on future directions of multi- and interdisciplinary studies is discussed. PMID:27513023

  17. Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep.

    PubMed

    Wei, Caihong; Wang, Huihua; Liu, Gang; Zhao, Fuping; Kijas, James W; Ma, Youji; Lu, Jian; Zhang, Li; Cao, Jiaxue; Wu, Mingming; Wang, Guangkai; Liu, Ruizao; Liu, Zhen; Zhang, Shuzhen; Liu, Chousheng; Du, Lixin

    2016-01-01

    Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3' untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation. PMID:27230812

  18. Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep

    PubMed Central

    Wei, Caihong; Wang, Huihua; Liu, Gang; Zhao, Fuping; Kijas, James W.; Ma, Youji; Lu, Jian; Zhang, Li; Cao, Jiaxue; Wu, Mingming; Wang, Guangkai; Liu, Ruizao; Liu, Zhen; Zhang, Shuzhen; Liu, Chousheng; Du, Lixin

    2016-01-01

    Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3′ untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation. PMID:27230812

  19. SUSCEPTIBILITY LOCI FOR UMBILICAL HERNIA IN SWINE DETECTED BY GENOME-WIDE ASSOCIATION.

    PubMed

    Liao, X J; Lia, L; Zhang, Z Y; Long, Y; Yang, B; Ruan, G R; Su, Y; Ai, H S; Zhang, W C; Deng, W Y; Xiao, S J; Ren, J; Ding, N S; Huang, L S

    2015-10-01

    Umbilical hernia (UH) is a complex disorder caused by both genetic and environmental factors. UH brings animal welfare problems and severe economic loss to the pig industry. Until now, the genetic basis of UH is poorly understood. The high-density 60K porcine SNP array enables the rapid application of genome-wide association study (GWAS) to identify genetic loci for phenotypic traits at genome wide scale in pigs. The objective of this research was to identify susceptibility loci for swine umbilical hernia using the GWAS approach. We genotyped 478 piglets from 142 families representing three Western commercial breeds with the Illumina PorcineSNP60 BeadChip. Then significant SNPs were detected by GWAS using ROADTRIPS (Robust Association-Detection Test for Related Individuals with Population Substructure) software base on a Bonferroni corrected threshold (P = 1.67E-06) or suggestive threshold (P = 3.34E-05) and false discovery rate (FDR = 0.05). After quality control, 29,924 qualified SNPs and 472 piglets were used for GWAS. Two suggestive loci predisposing to pig UH were identified at 44.25MB on SSC2 (rs81358018, P = 3.34E-06, FDR = 0.049933) and at 45.90MB on SSC17 (rs81479278, P = 3.30E-06, FDR = 0.049933) in Duroc population, respectively. And no SNP was detected to be associated with pig UH at significant level in neither Landrace nor Large White population. Furthermore, we carried out a meta-analysis in the combined pure-breed population containing all the 472 piglets. rs81479278 (P = 1.16E-06, FDR = 0.022475) was identified to associate with pig UH at genome-wide significant level. SRC was characterized as plausible candidate gene for susceptibility to pig UH according to its genomic position and biological functions. To our knowledge, this study gives the first description of GWAS identifying susceptibility loci for umbilical hernia in pigs. Our findings provide deeper insights to the genetic architecture of umbilical hernia in pigs. PMID:27169231

  20. The identification of 14 new genes for meat quality traits in chicken using a genome-wide association study

    PubMed Central

    2013-01-01

    Background Meat quality is an important economic trait in chickens. To identify loci and genes associated with meat quality traits, we conducted a genome-wide association study (GWAS) of F2 populations derived from a local Chinese breed (Beijing-You chickens) and a commercial fast-growing broiler line (Cobb-Vantress). Results In the present study, 33 association signals were detected from the compressed mixed linear model (MLM) for 10 meat quality traits: dry matter in breast muscle (DMBr), dry matter in thigh muscle (DMTh), intramuscular fat content in breast muscle (IMFBr), meat color lightness (L*) and yellowness (b*) values, skin color L*, a* (redness) and b* values, abdominal fat weight (AbFW) and AbFW as a percentage of eviscerated weight (AbFP). Relative expressions of candidate genes identified near significant signals were compared using samples of chickens with High and Low phenotypic values. A total of 14 genes associated with IMFBr, meat color L*, AbFW, and AbFP, were differentially expressed between the High and Low phenotypic groups. These genes are, therefore, prospective candidate genes for meat quality traits: protein tyrosine kinase (TYRO3) and microsomal glutathione S-transferase 1 (MGST1) for IMFBr; collagen, type I, alpha 2 (COL1A2) for meat color L*; and RET proto-oncogene (RET), natriuretic peptide B (NPPB) and sterol regulatory element binding transcription factor 1 (SREBF1) for the abdominal fat (AbF) traits. Conclusions Based on the association signals and differential expression of nearby genes, 14 candidate loci and genes for IMFBr, meat L* and b* values, and AbF are identified. The results provide new insight into the molecular mechanisms underlying meat quality traits in chickens. PMID:23834466

  1. A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

    PubMed Central

    Loukola, Anu; Buchwald, Jadwiga; Gupta, Richa; Palviainen, Teemu; Hällfors, Jenni; Tikkanen, Emmi; Korhonen, Tellervo; Ollikainen, Miina; Sarin, Antti-Pekka; Ripatti, Samuli; Lehtimäki, Terho; Raitakari, Olli; Salomaa, Veikko; Rose, Richard J.; Tyndale, Rachel F.; Kaprio, Jaakko

    2015-01-01

    Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70–0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FINRISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence

  2. First WNK4-Hypokalemia Animal Model Identified by Genome-Wide Association in Burmese Cats

    PubMed Central

    Gandolfi, Barbara; Gruffydd-Jones, Timothy J.; Malik, Richard; Cortes, Alejandro; Jones, Boyd R.; Helps, Chris R.; Prinzenberg, Eva M.; Erhardt, George; Lyons, Leslie A.

    2012-01-01

    Burmese is an old and popular cat breed, however, several health concerns, such as hypokalemia and a craniofacial defect, are prevalent, endangering the general health of the breed. Hypokalemia, a subnormal serum potassium ion concentration ([K+]), most often occurs as a secondary problem but can occur as a primary problem, such as hypokalaemic periodic paralysis in humans, and as feline hypokalaemic periodic polymyopathy primarily in Burmese. The most characteristic clinical sign of hypokalemia in Burmese is a skeletal muscle weakness that is frequently episodic in nature, either generalized, or sometimes localized to the cervical and thoracic limb girdle muscles. Burmese hypokalemia is suspected to be a single locus autosomal recessive trait. A genome wide case-control study using the illumina Infinium Feline 63K iSelect DNA array was performed using 35 cases and 25 controls from the Burmese breed that identified a locus on chromosome E1 associated with hypokalemia. Within approximately 1.2 Mb of the highest associated SNP, two candidate genes were identified, KCNH4 and WNK4. Direct sequencing of the genes revealed a nonsense mutation, producing a premature stop codon within WNK4 (c.2899C>T), leading to a truncated protein that lacks the C-terminal coiled-coil domain and the highly conserved Akt1/SGK phosphorylation site. All cases were homozygous for the mutation. Although the exact mechanism causing hypokalemia has not been determined, extrapolation from the homologous human and mouse genes suggests the mechanism may involve a potassium-losing nephropathy. A genetic test to screen for the genetic defect within the active breeding population has been developed, which should lead to eradication of the mutation and improved general health within the breed. Moreover, the identified mutation may help clarify the role of the protein in K+ regulation and the cat represents the first animal model for WNK4-associated hypokalemia. PMID:23285264

  3. Genome-Wide Scan for Methylation Profiles in Keloids

    PubMed Central

    Jones, Lamont R.; Young, William; Divine, George; Datta, Indrani; Chen, Kang Mei; Ozog, David; Worsham, Maria J.

    2015-01-01

    Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation. PMID:26074660

  4. Genome-wide association interaction analysis for Alzheimer's disease

    PubMed Central

    Gusareva, Elena S.; Carrasquillo, Minerva M.; Bellenguez, Céline; Cuyvers, Elise; Colon, Samuel; Graff-Radford, Neill R.; Petersen, Ronald C.; Dickson, Dennis W.; Mahachie Johna, Jestinah M.; Bessonov, Kyrylo; Van Broeckhoven, Christine; Williams, Julie; Amouyel, Philippe; Sleegers, Kristel; Ertekin-Taner, Nilüfer; Lambert, Jean-Charles; Van Steen, Kristel

    2015-01-01

    We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = −0.19, p = 0.0006) and cerebellum (β = −0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. PMID:24958192

  5. A Genome-Wide Association Study of Aging

    PubMed Central

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W.; Garcia, Melissa E.; Kaplan, Robert C.; Kumari, Meena; Lunetta, Kathryn L.; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J.; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J.; Biffar, Reiner; Buchman, Aron S.; Boerwinkle, Eric; Couper, David; De Jager, Philip L.; Evans, Denis A.; Harris, Tamara B.; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P.; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J.; Lohman, Kurt K.; Lutsey, Pamela L.; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M.; Reiman, Eric M.; Rotter, Jerome I.; Seshadri, Sudha; Shardell, Michelle D.; Smith, Albert V.; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M. Carola; Bandinelli, Stefania; Baumeister, Sebastian E.; Bennett, David A.; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M.; Newman, Anne B.; Tiemeier, Henning; Franceschini, Nora

    2011-01-01

    Human longevity and healthy aging show moderate heritability (20–50%). We conducted a meta-analysis of genome-wide association studies from nine studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for two outcomes: a) all-cause mortality and b) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found fourteen independent SNPs that predicted risk of death, and eight SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer’s disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity. PMID:21782286

  6. Consistency of genome-wide associations across major ancestral groups.

    PubMed

    Ntzani, Evangelia E; Liberopoulos, George; Manolio, Teri A; Ioannidis, John P A

    2012-07-01

    It is not well known whether genetic markers identified through genome-wide association studies (GWAS) confer similar or different risks across people of different ancestry. We screened a regularly updated catalog of all published GWAS curated at the NHGRI website for GWAS-identified associations that had reached genome-wide significance (p ≤ 5 × 10(-8)) in at least one major ancestry group (European, Asian, African) and for which replication data were available for comparison in at least two different major ancestry groups. These groups were compared for the correlation between and differences in risk allele frequencies and genetic effects' estimates. Data on 108 eligible GWAS-identified associations with a total of 900 datasets (European, n = 624; Asian, n = 217; African, n = 60) were analyzed. Risk-allele frequencies were modestly correlated between ancestry groups, with >10% absolute differences in 75-89% of the three pairwise comparisons of ancestry groups. Genetic effect (odds ratio) point estimates between ancestry groups correlated modestly (pairwise comparisons' correlation coefficients: 0.20-0.33) and point estimates of risks were opposite in direction or differed more than twofold in 57%, 79%, and 89% of the European versus Asian, European versus African, and Asian versus African comparisons, respectively. The modest correlations, differing risk estimates, and considerable between-association heterogeneity suggest that differential ancestral effects can be anticipated and genomic risk markers may need separate further evaluation in different ancestry groups. PMID:22183176

  7. Phenome-wide analysis of genome-wide polygenic scores.

    PubMed

    Krapohl, E; Euesden, J; Zabaneh, D; Pingault, J-B; Rimfeld, K; von Stumm, S; Dale, P S; Breen, G; O'Reilly, P F; Plomin, R

    2016-09-01

    Genome-wide polygenic scores (GPS), which aggregate the effects of thousands of DNA variants from genome-wide association studies (GWAS), have the potential to make genetic predictions for individuals. We conducted a systematic investigation of associations between GPS and many behavioral traits, the behavioral phenome. For 3152 unrelated 16-year-old individuals representative of the United Kingdom, we created 13 GPS from the largest GWAS for psychiatric disorders (for example, schizophrenia, depression and dementia) and cognitive traits (for example, intelligence, educational attainment and intracranial volume). The behavioral phenome included 50 traits from the domains of psychopathology, personality, cognitive abilities and educational achievement. We examined phenome-wide profiles of associations for the entire distribution of each GPS and for the extremes of the GPS distributions. The cognitive GPS yielded stronger predictive power than the psychiatric GPS in our UK-representative sample of adolescents. For example, education GPS explained variation in adolescents' behavior problems (~0.6%) and in educational achievement (~2%) but psychiatric GPS were associated with neither. Despite the modest effect sizes of current GPS, quantile analyses illustrate the ability to stratify individuals by GPS and opportunities for research. For example, the highest and lowest septiles for the education GPS yielded a 0.5 s.d. difference in mean math grade and a 0.25 s.d. difference in mean behavior problems. We discuss the usefulness and limitations of GPS based on adult GWAS to predict genetic propensities earlier in development. PMID:26303664

  8. Genome-wide identification of hypoxia-induced enhancer regions

    PubMed Central

    Preston, Jessica L.; Randel, Melissa A.; Johnson, Eric A.

    2015-01-01

    Here we present a genome-wide method for de novo identification of enhancer regions. This approach enables massively parallel empirical investigation of DNA sequences that mediate transcriptional activation and provides a platform for discovery of regulatory modules capable of driving context-specific gene expression. The method links fragmented genomic DNA to the transcription of randomer molecule identifiers and measures the functional enhancer activity of the library by massively parallel sequencing. We transfected a Drosophila melanogaster library into S2 cells in normoxia and hypoxia, and assayed 4,599,881 genomic DNA fragments in parallel. The locations of the enhancer regions strongly correlate with genes up-regulated after hypoxia and previously described enhancers. Novel enhancer regions were identified and integrated with RNAseq data and transcription factor motifs to describe the hypoxic response on a genome-wide basis as a complex regulatory network involving multiple stress-response pathways. This work provides a novel method for high-throughput assay of enhancer activity and the genome-scale identification of 31 hypoxia-activated enhancers in Drosophila. PMID:26713262

  9. Genome-wide analysis of DNA methylation in hepatoblastoma tissues

    PubMed Central

    Cui, Ximao; Liu, Baihui; Zheng, Shan; Dong, Kuiran; Dong, Rui

    2016-01-01

    DNA methylation has a crucial role in cancer biology. In the present study, a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues was performed to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, AFP methylation levels were also detected using pyrosequencing. Normal and HB liver tissue samples (frozen tissue) were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation450 BeadChip, and the results were confirmed with reverse transcription-quantitative polymerase chain reaction. The Infinium HumanMethylation450 BeadChip demonstrated distinctively less methylation in HB tissues than in non-tumor tissues. In addition, methylation enrichment was observed in positions near the transcription start site of AFP, which exhibited lower methylation levels in HB tissues than in non-tumor liver tissues. Lastly, a significant negative correlation was observed between AFP messenger RNA expression and DNA methylation percentage, using linear Pearson's R correlation coefficients. The present results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of AFP in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology. PMID:27446465

  10. Genome-wide association study of Tourette's syndrome.

    PubMed

    Scharf, J M; Yu, D; Mathews, C A; Neale, B M; Stewart, S E; Fagerness, J A; Evans, P; Gamazon, E; Edlund, C K; Service, S K; Tikhomirov, A; Osiecki, L; Illmann, C; Pluzhnikov, A; Konkashbaev, A; Davis, L K; Han, B; Crane, J; Moorjani, P; Crenshaw, A T; Parkin, M A; Reus, V I; Lowe, T L; Rangel-Lugo, M; Chouinard, S; Dion, Y; Girard, S; Cath, D C; Smit, J H; King, R A; Fernandez, T V; Leckman, J F; Kidd, K K; Kidd, J R; Pakstis, A J; State, M W; Herrera, L D; Romero, R; Fournier, E; Sandor, P; Barr, C L; Phan, N; Gross-Tsur, V; Benarroch, F; Pollak, Y; Budman, C L; Bruun, R D; Erenberg, G; Naarden, A L; Lee, P C; Weiss, N; Kremeyer, B; Berrío, G B; Campbell, D D; Cardona Silgado, J C; Ochoa, W C; Mesa Restrepo, S C; Muller, H; Valencia Duarte, A V; Lyon, G J; Leppert, M; Morgan, J; Weiss, R; Grados, M A; Anderson, K; Davarya, S; Singer, H; Walkup, J; Jankovic, J; Tischfield, J A; Heiman, G A; Gilbert, D L; Hoekstra, P J; Robertson, M M; Kurlan, R; Liu, C; Gibbs, J R; Singleton, A; Hardy, J; Strengman, E; Ophoff, R A; Wagner, M; Moessner, R; Mirel, D B; Posthuma, D; Sabatti, C; Eskin, E; Conti, D V; Knowles, J A; Ruiz-Linares, A; Rouleau, G A; Purcell, S; Heutink, P; Oostra, B A; McMahon, W M; Freimer, N B; Cox, N J; Pauls, D L

    2013-06-01

    Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  11. Genome-Wide Patterns of Nucleotide Polymorphism in Domesticated Rice

    PubMed Central

    Hernandez, Ryan D; Boyko, Adam; Fledel-Alon, Adi; York, Thomas L; Polato, Nicholas R; Olsen, Kenneth M; Nielsen, Rasmus; McCouch, Susan R; Bustamante, Carlos D; Purugganan, Michael D

    2007-01-01

    Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models to explain contemporary patterns of polymorphisms in rice, including a (i) selectively neutral population bottleneck model, (ii) bottleneck plus migration model, (iii) multiple selective sweeps model, and (iv) bottleneck plus selective sweeps model. We find that a simple bottleneck model, which has been the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible explanations for patterns of variation in domesticated rice varieties. If selective sweeps are indeed the explanation for the observed nucleotide data of domesticated rice, it suggests that strong selection can leave its imprint on genome-wide polymorphism patterns, contrary to expectations that selection results only in a local signature of variation. PMID:17907810

  12. Genome-wide signals of positive selection in human evolution

    PubMed Central

    Enard, David; Messer, Philipp W.; Petrov, Dmitri A.

    2014-01-01

    The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes. PMID:24619126

  13. Genome-wide association study of Tourette Syndrome

    PubMed Central

    Scharf, Jeremiah M.; Yu, Dongmei; Mathews, Carol A.; Neale, Benjamin M.; Stewart, S. Evelyn; Fagerness, Jesen A; Evans, Patrick; Gamazon, Eric; Edlund, Christopher K.; Service, Susan; Tikhomirov, Anna; Osiecki, Lisa; Illmann, Cornelia; Pluzhnikov, Anna; Konkashbaev, Anuar; Davis, Lea K; Han, Buhm; Crane, Jacquelyn; Moorjani, Priya; Crenshaw, Andrew T.; Parkin, Melissa A.; Reus, Victor I.; Lowe, Thomas L.; Rangel-Lugo, Martha; Chouinard, Sylvain; Dion, Yves; Girard, Simon; Cath, Danielle C; Smit, Jan H; King, Robert A.; Fernandez, Thomas; Leckman, James F.; Kidd, Kenneth K.; Kidd, Judith R.; Pakstis, Andrew J.; State, Matthew; Herrera, Luis Diego; Romero, Roxana; Fournier, Eduardo; Sandor, Paul; Barr, Cathy L; Phan, Nam; Gross-Tsur, Varda; Benarroch, Fortu; Pollak, Yehuda; Budman, Cathy L.; Bruun, Ruth D.; Erenberg, Gerald; Naarden, Allan L; Lee, Paul C; Weiss, Nicholas; Kremeyer, Barbara; Berrío, Gabriel Bedoya; Campbell, Desmond; Silgado, Julio C. Cardona; Ochoa, William Cornejo; Restrepo, Sandra C. Mesa; Muller, Heike; Duarte, Ana V. Valencia; Lyon, Gholson J; Leppert, Mark; Morgan, Jubel; Weiss, Robert; Grados, Marco A.; Anderson, Kelley; Davarya, Sarah; Singer, Harvey; Walkup, John; Jankovic, Joseph; Tischfield, Jay A.; Heiman, Gary A.; Gilbert, Donald L.; Hoekstra, Pieter J.; Robertson, Mary M.; Kurlan, Roger; Liu, Chunyu; Gibbs, J. Raphael; Singleton, Andrew; Hardy, John; Strengman, Eric; Ophoff, Roel; Wagner, Michael; Moessner, Rainald; Mirel, Daniel B.; Posthuma, Danielle; Sabatti, Chiara; Eskin, Eleazar; Conti, David V.; Knowles, James A.; Ruiz-Linares, Andres; Rouleau, Guy A.; Purcell, Shaun; Heutink, Peter; Oostra, Ben A.; McMahon, William; Freimer, Nelson; Cox, Nancy J.; Pauls, David L.

    2012-01-01

    Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  14. Genome-wide association analysis identifies three psoriasis susceptibility loci

    PubMed Central

    Stuart, Philip E.; Nair, Rajan P.; Ellinghaus, Eva; Ding, Jun; Tejasvi, Trilokraj; Gudjonsson, Johann E.; Li, Yun; Weidinger, Stephan; Eberlein, Bernadette; Gieger, Christian; Wichmann, H. Erich; Kunz, Manfred; Ike, Robert; Krueger, Gerald G.; Bowcock, Anne M.; Mroweitz, Ulrich; Lim, Henry W.; Voorhees, John J.; Abecasis, Goncalo R.; Weichenthal, Michael; Franke, Andre; Rahman, Proton; Gladman, Dafna D.; Elder, James T.

    2010-01-01

    To identify novel psoriasis susceptibility loci, we carried out a meta-analysis of two recent genome-wide association studies 1,2, yielding a discovery sample of 1,831 cases and 2,546 controls. 102 of the most promising loci in the discovery analysis were followed up in a three-stage replication study using 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland, and Germany. Association at a genome-wide level of significance for the combined discovery and replication samples was found for three genomic regions. One contains NOS2 (rs4795067, p = 4 × 10−11), another contains FBXL19 (rs10782001, p = 9 × 10−10), and a third contains PSMA6 and NFKBIA (rs12586317, p = 2 × 10−8). All three loci were also strongly associated with the subphenotypes of psoriatic arthritis and purely cutaneous psoriasis. Finally, we confirmed a recently identified3 association signal near RNF114. PMID:20953189

  15. Establishing an analytic pipeline for genome-wide DNA methylation.

    PubMed

    Wright, Michelle L; Dozmorov, Mikhail G; Wolen, Aaron R; Jackson-Cook, Colleen; Starkweather, Angela R; Lyon, Debra E; York, Timothy P

    2016-01-01

    The need for research investigating DNA methylation (DNAm) in clinical studies has increased, leading to the evolution of new analytic methods to improve accuracy and reproducibility of the interpretation of results from these studies. The purpose of this article is to provide clinical researchers with a summary of the major data processing steps routinely applied in clinical studies investigating genome-wide DNAm using the Illumina HumanMethylation 450K BeadChip. In most studies, the primary goal of employing DNAm analysis is to identify differential methylation at CpG sites among phenotypic groups. Experimental design considerations are crucial at the onset to minimize bias from factors related to sample processing and avoid confounding experimental variables with non-biological batch effects. Although there are currently no de facto standard methods for analyzing these data, we review the major steps in processing DNAm data recommended by several research studies. We describe several variations available for clinical researchers to process, analyze, and interpret DNAm data. These insights are applicable to most types of genome-wide DNAm array platforms and will be applicable for the next generation of DNAm array technologies (e.g., the 850K array). Selection of the DNAm analytic pipeline followed by investigators should be guided by the research question and supported by recently published methods. PMID:27127542

  16. Advances in genome-wide DNA methylation analysis

    PubMed Central

    Gupta, Romi; Nagarajan, Arvindhan; Wajapeyee, Narendra

    2013-01-01

    The covalent DNA modification of cytosine at position 5 (5-methylcytosine; 5mC) has emerged as an important epigenetic mark most commonly present in the context of CpG dinucleotides in mammalian cells. In pluripotent stem cells and plants, it is also found in non-CpG and CpNpG contexts, respectively. 5mC has important implications in a diverse set of biological processes, including transcriptional regulation. Aberrant DNA methylation has been shown to be associated with a wide variety of human ailments and thus is the focus of active investigation. Methods used for detecting DNA methylation have revolutionized our understanding of this epigenetic mark and provided new insights into its role in diverse biological functions. Here we describe recent technological advances in genome-wide DNA methylation analysis and discuss their relative utility and drawbacks, providing specific examples from studies that have used these technologies for genome-wide DNA methylation analysis to address important biological questions. Finally, we discuss a newly identified covalent DNA modification, 5-hydroxymethylcytosine (5hmC), and speculate on its possible biological function, as well as describe a new methodology that can distinguish 5hmC from 5mC. PMID:20964631

  17. Measuring genome-wide nucleosome turnover using CATCH-IT.

    PubMed

    Teves, Sheila S; Deal, Roger B; Henikoff, Steven

    2012-01-01

    The dynamic interplay between DNA-binding proteins and nucleosomes underlies essential nuclear processes such as transcription, replication, and DNA repair. Manifestations of this interplay include the assembly, eviction, and replacement of nucleosomes. Hence, measurements of nucleosome turnover kinetics can lead to insights into the regulation of dynamic chromatin processes. In this chapter, we describe a genome-wide method for measuring nucleosome turnover that uses metabolic labeling followed by capture of newly synthesized histones, which we have termed Covalent Attachment of Tagged Histones to Capture and Identify Turnover (CATCH-IT). Although CATCH-IT can be used with any genome-wide mapping procedure, high-resolution profiling is attainable using paired-end sequencing of native chromatin. Our protocol also includes an efficient Solexa DNA sequencing library preparation protocol that can be used for single base-pair resolution mapping of both nucleosome and subnucleosomal particles. We not only describe the use of these protocols in the context of a Drosophila cell line but also provide the necessary changes for adaptation to other model systems. PMID:22929769

  18. Genome-Wide Mapping of DNA Strand Breaks

    PubMed Central

    Leduc, Frédéric; Faucher, David; Bikond Nkoma, Geneviève; Grégoire, Marie-Chantal; Arguin, Mélina; Wellinger, Raymund J.; Boissonneault, Guylain

    2011-01-01

    Determination of cellular DNA damage has so far been limited to global assessment of genome integrity whereas nucleotide-level mapping has been restricted to specific loci by the use of specific primers. Therefore, only limited DNA sequences can be studied and novel regions of genomic instability can hardly be discovered. Using a well-characterized yeast model, we describe a straightforward strategy to map genome-wide DNA strand breaks without compromising nucleotide-level resolution. This technique, termed “damaged DNA immunoprecipitation” (dDIP), uses immunoprecipitation and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling (TUNEL) to capture DNA at break sites. When used in combination with microarray or next-generation sequencing technologies, dDIP will allow researchers to map genome-wide DNA strand breaks as well as other types of DNA damage and to establish a clear profiling of altered genes and/or intergenic sequences in various experimental conditions. This mapping technique could find several applications for instance in the study of aging, genotoxic drug screening, cancer, meiosis, radiation and oxidative DNA damage. PMID:21364894

  19. Genome-wide association studies and prediction of 17 traits related to phenology, biomass and cell wall composition in the energy grass Miscanthus sinensis

    PubMed Central

    Slavov, Gancho T; Nipper, Rick; Robson, Paul; Farrar, Kerrie; Allison, Gordon G; Bosch, Maurice; Clifton-Brown, John C; Donnison, Iain S; Jensen, Elaine

    2014-01-01

    Increasing demands for food and energy require a step change in the effectiveness, speed and flexibility of crop breeding. Therefore, the aim of this study was to assess the potential of genome-wide association studies (GWASs) and genomic selection (i.e. phenotype prediction from a genome-wide set of markers) to guide fundamental plant science and to accelerate breeding in the energy grass Miscanthus. We generated over 100 000 single-nucleotide variants (SNVs) by sequencing restriction site-associated DNA (RAD) tags in 138 Micanthus sinensis genotypes, and related SNVs to phenotypic data for 17 traits measured in a field trial. Confounding by population structure and relatedness was severe in naïve GWAS analyses, but mixed-linear models robustly controlled for these effects and allowed us to detect multiple associations that reached genome-wide significance. Genome-wide prediction accuracies tended to be moderate to high (average of 0.57), but varied dramatically across traits. As expected, predictive abilities increased linearly with the size of the mapping population, but reached a plateau when the number of markers used for prediction exceeded 10 000–20 000, and tended to decline, but remain significant, when cross-validations were performed across subpopulations. Our results suggest that the immediate implementation of genomic selection in Miscanthus breeding programs may be feasible. PMID:24308815

  20. Economic values of body weight, reproduction and parasite resistance traits for a Creole goat breeding goal.

    PubMed

    Gunia, M; Mandonnet, N; Arquet, R; Alexandre, G; Gourdine, J-L; Naves, M; Angeon, V; Phocas, F

    2013-01-01

    A specific breeding goal definition was developed for Creole goats in Guadeloupe. This local breed is used for meat production. To ensure a balanced selection outcome, the breeding objective included two production traits, live weight (BW11) and dressing percentage (DP) at 11 months (the mating or selling age), one reproduction trait, fertility (FER), and two traits to assess animal response to parasite infection: packed cell volume (PCV), a resilience trait, and faecal worm eggs count (FEC), a resistance trait. A deterministic bio-economic model was developed to calculate the economic values based on the description of the profit of a Guadeloupean goat farm. The farm income came from the sale of animals for meat or as reproducers. The main costs were feeding and treatments against gastro-intestinal parasites. The economic values were 7.69€ per kg for BW11, 1.38€ per % for FER, 3.53€ per % for DP and 3 × 10(-4)€ per % for PCV. The economic value for FEC was derived by comparing the expected profit and average FEC in a normal situation and in an extreme situation where parasites had developed resistance to anthelmintics. This method yielded a maximum weighting for FEC, which was -18.85€ per log(eggs per gram). Alternative scenarios were tested to assess the robustness of the economic values to variations in the economic and environmental context. The economic values of PCV and DP were the most stable. Issues involved in paving the way for selective breeding on resistance or resilience to parasites are discussed. PMID:23031546

  1. Genome-wide association study of antisocial personality disorder.

    PubMed

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  2. A Genome-Wide Association Study of Optic Disc Parameters

    PubMed Central

    Jansonius, Nomdo M.; de Jong, Paulus T. V. M.; Bergen, Arthur A. B.; Isaacs, Aaron; Amin, Najaf; Aulchenko, Yurii S.; Wolfs, Roger C. W.; Hofman, Albert; Rivadeneira, Fernando; Oostra, Ben A.; Uitterlinden, Andre G.; Hysi, Pirro; Hammond, Christopher J.; Lemij, Hans G.; Vingerling, Johannes R.

    2010-01-01

    The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72×10−19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67×10−33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15×10−11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93×10−10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin. PMID:20548946

  3. Genome-wide assessment of Parkinson's disease in a Southern Spanish population.

    PubMed

    Bandrés-Ciga, Sara; Price, Timothy Ryan; Barrero, Francisco Javier; Escamilla-Sevilla, Francisco; Pelegrina, Javier; Arepalli, Sampath; Hernández, Dena; Gutiérrez, Blanca; Cervilla, Jorge; Rivera, Margarita; Rivera, Alberto; Ding, Jing-Hui; Vives, Francisco; Nalls, Michael; Singleton, Andrew; Durán, Raquel

    2016-09-01

    Here, we set out to study the genetic architecture of Parkinson's disease (PD) through a Genome-Wide Association Study in a Southern Spanish population. About 240 PD cases and 192 controls were genotyped on the NeuroX array. We estimated genetic variation associated with PD risk and age at onset (AAO). Risk profile analyses for PD and AAO were performed using a weighted genetic risk score. Total heritability was estimated by genome-wide complex trait analysis. Rare variants were screened with single-variant and burden tests. We also screened for variation in known PD genes. Finally, we explored runs of homozygosity and structural genomic variations. We replicate PD association (uncorrected p-value < 0.05) at the following loci: ACMSD/TMEM163, MAPT, STK39, MIR4697, and SREBF/RAI1. Subjects in the highest genetic risk score quintile showed significantly increased risk of PD versus the lowest quintile (odds ratio = 3.6, p-value < 4e(-7)), but no significant difference in AAO. We found evidence of runs of homozygosity in 2 PD-associated regions: one intersecting the HLA-DQB1 gene in 6 patients and 1 control; and another intersecting the GBA-SYT11 gene in PD case. The GBA N370S and the LRRK2 G2019S variants were found in 8 and 7 cases, respectively, replicating previous work. A structural variant was found in 1 case in the PARK2 gene locus. This current work represents a comprehensive assessment at a genome-wide level characterizing a novel population in PD genetics. PMID:27393345

  4. Prediction of breeding values for dairy cattle using artificial neural networks and neuro-fuzzy systems.

    PubMed

    Shahinfar, Saleh; Mehrabani-Yeganeh, Hassan; Lucas, Caro; Kalhor, Ahmad; Kazemian, Majid; Weigel, Kent A

    2012-01-01

    Developing machine learning and soft computing techniques has provided many opportunities for researchers to establish new analytical methods in different areas of science. The objective of this study is to investigate the potential of two types of intelligent learning methods, artificial neural networks and neuro-fuzzy systems, in order to estimate breeding values (EBV) of Iranian dairy cattle. Initially, the breeding values of lactating Holstein cows for milk and fat yield were estimated using conventional best linear unbiased prediction (BLUP) with an animal model. Once that was established, a multilayer perceptron was used to build ANN to predict breeding values from the performance data of selection candidates. Subsequently, fuzzy logic was used to form an NFS, a hybrid intelligent system that was implemented via a local linear model tree algorithm. For milk yield the correlations between EBV and EBV predicted by the ANN and NFS were 0.92 and 0.93, respectively. Corresponding correlations for fat yield were 0.93 and 0.93, respectively. Correlations between multitrait predictions of EBVs for milk and fat yield when predicted simultaneously by ANN were 0.93 and 0.93, respectively, whereas corresponding correlations with reference EBV for multitrait NFS were 0.94 and 0.95, respectively, for milk and fat production. PMID:22991575

  5. Genome-Wide Patterns of Genetic Variation in Two Domestic Chickens

    PubMed Central

    Fan, Wen-Lang; Ng, Chen Siang; Chen, Chih-Feng; Lu, Mei-Yeh Jade; Chen, Yu-Hsiang; Liu, Chia-Jung; Wu, Siao-Man; Chen, Chih-Kuan; Chen, Jiun-Jie; Mao, Chi-Tang; Lai, Yu-Ting; Lo, Wen-Sui; Chang, Wei-Hua; Li, Wen-Hsiung

    2013-01-01

    Domestic chickens are excellent models for investigating the genetic basis of phenotypic diversity, as numerous phenotypic changes in physiology, morphology, and behavior in chickens have been artificially selected. Genomic study is required to study genome-wide patterns of DNA variation for dissecting the genetic basis of phenotypic traits. We sequenced the genomes of the Silkie and the Taiwanese native chicken L2 at ∼23- and 25-fold average coverage depth, respectively, using Illumina sequencing. The reads were mapped onto the chicken reference genome (including 5.1% Ns) to 92.32% genome coverage for the two breeds. Using a stringent filter, we identified ∼7.6 million single-nucleotide polymorphisms (SNPs) and 8,839 copy number variations (CNVs) in the mapped regions; 42% of the SNPs have not found in other chickens before. Among the 68,906 SNPs annotated in the chicken sequence assembly, 27,852 were nonsynonymous SNPs located in 13,537 genes. We also identified hundreds of shared and divergent structural and copy number variants in intronic and intergenic regions and in coding regions in the two breeds. Functional enrichments of identified genetic variants were discussed. Radical nsSNP-containing immunity genes were enriched in the QTL regions associated with some economic traits for both breeds. Moreover, genetic changes involved in selective sweeps were detected. From the selective sweeps identified in our two breeds, several genes associated with growth, appetite, and metabolic regulation were identified. Our study provides a framework for genetic and genomic research of domestic chickens and facilitates the domestic chicken as an avian model for genomic, biomedical, and evolutionary studies. PMID:23814129

  6. Quantitative prediction of genome-wide resource allocation in bacteria.

    PubMed

    Goelzer, Anne; Muntel, Jan; Chubukov, Victor; Jules, Matthieu; Prestel, Eric; Nölker, Rolf; Mariadassou, Mahendra; Aymerich, Stéphane; Hecker, Michael; Noirot, Philippe; Becher, Dörte; Fromion, Vincent

    2015-11-01

    Predicting resource allocation between cell processes is the primary step towards decoding the evolutionary constraints governing bacterial growth under various conditions. Quantitative prediction at genome-scale remains a computational challenge as current methods are limited by the tractability of the problem or by simplifying hypotheses. Here, we show that the constraint-based modeling method Resource Balance Analysis (RBA), calibrated using genome-wide absolute protein quantification data, accurately predicts resource allocation in the model bacterium Bacillus subtilis for a wide range of growth conditions. The regulation of most cellular processes is consistent with the objective of growth rate maximization except for a few suboptimal processes which likely integrate more complex objectives such as coping with stressful conditions and survival. As a proof of principle by using simulations, we illustrated how calibrated RBA could aid rational design of strains for maximizing protein production, offering new opportunities to investigate design principles in prokaryotes and to exploit them for biotechnological applications. PMID:26498510

  7. Metabolite-based genome-wide association studies in plants.

    PubMed

    Luo, Jie

    2015-04-01

    The plant metabolome is the readout of plant physiological status and is regarded as the bridge between the genome and the phenome of plants. Unraveling the natural variation and the underlying genetic basis of plant metabolism has received increasing interest from plant biologists. Enabled by the recent advances in high-throughput profiling and genotyping technologies, metabolite-based genome-wide association study (mGWAS) has emerged as a powerful alternative forward genetics strategy to dissect the genetic and biochemical bases of metabolism in model and crop plants. In this review, recent progress and applications of mGWAS in understanding the genetic control of plant metabolism and in interactive functional genomics and metabolomics are presented. Further directions and perspectives of mGWAS in plants are also discussed. PMID:25637954

  8. Genome-wide association studies in pediatric chronic kidney disease.

    PubMed

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression. PMID:26490952

  9. Ultrafast laser nanosurgery in microfluidics for genome-wide screenings

    PubMed Central

    Ben-Yakar, Adela; Bourgeois, Frederic

    2009-01-01

    Summary The use of ultrafast laser pulses in surgery has allowed for unprecedented precision with minimal collateral damage to surrounding tissues. For these reasons, ultrafast laser nanosurgery, as an injury model, has gained tremendous momentum in experimental biology ranging from in-vitro manipulations of subcellular structures to in-vivo studies in whole living organisms. For example, femtosecond laser nanosurgery on such model organism as the nematode Caenorhabditis elegans (C. elegans) has opened new opportunities for in-vivo nerve regeneration studies. Meanwhile, the development of novel microfluidic devices has brought the control in experimental environment to the level required for precise nanosurgery in various animal models. Merging microfluidics and laser nanosurgery has recently improved the specificities and increased the speed of laser surgeries enabling fast genome-wide screenings that can more readily decode the genetic map of various biological processes. PMID:19278850

  10. Genome-wide nucleosome positioning during embryonic stem cell development.

    PubMed

    Teif, Vladimir B; Vainshtein, Yevhen; Caudron-Herger, Maïwen; Mallm, Jan-Philipp; Marth, Caroline; Höfer, Thomas; Rippe, Karsten

    2012-11-01

    We determined genome-wide nucleosome occupancies in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell-type- and protein-specific binding preferences of transcription factors to sites with either low (Myc, Klf4 and Zfx) or high (Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome-depleted regions around transcription start and transcription termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to CpG content or histone methylation marks. Throughout the genome, nucleosome occupancy was correlated with certain histone methylation or acetylation modifications. In addition, the average nucleosome repeat length increased during differentiation by 5-7 base pairs, with local variations for specific regions. Our results reveal regulatory mechanisms of cell differentiation that involve nucleosome repositioning. PMID:23085715