共查询到20条相似文献,搜索用时 390 毫秒
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Genome-wide association study of quantitative resistance to southern leaf blight in the maize nested association mapping population 总被引:6,自引:0,他引:6
Kump KL Bradbury PJ Wisser RJ Buckler ES Belcher AR Oropeza-Rosas MA Zwonitzer JC Kresovich S McMullen MD Ware D Balint-Kurti PJ Holland JB 《Nature genetics》2011,43(2):163-168
Nested association mapping (NAM) offers power to resolve complex, quantitative traits to their causal loci. The maize NAM population, consisting of 5,000 recombinant inbred lines (RILs) from 25 families representing the global diversity of maize, was evaluated for resistance to southern leaf blight (SLB) disease. Joint-linkage analysis identified 32 quantitative trait loci (QTLs) with predominantly small, additive effects on SLB resistance. Genome-wide association tests of maize HapMap SNPs were conducted by imputing founder SNP genotypes onto the NAM RILs. SNPs both within and outside of QTL intervals were associated with variation for SLB resistance. Many of these SNPs were within or near sequences homologous to genes previously shown to be involved in plant disease resistance. Limited linkage disequilibrium was observed around some SNPs associated with SLB resistance, indicating that the maize NAM population enables high-resolution mapping of some genome regions. 相似文献
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Genome-wide association studies of 14 agronomic traits in rice landraces 总被引:20,自引:0,他引:20
Huang X Wei X Sang T Zhao Q Feng Q Zhao Y Li C Zhu C Lu T Zhang Z Li M Fan D Guo Y Wang A Wang L Deng L Li W Lu Y Weng Q Liu K Huang T Zhou T Jing Y Li W Lin Z Buckler ES Qian Q Zhang QF Li J Han B 《Nature genetics》2010,42(11):961-967
Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ~ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ~ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice. 相似文献
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Kerkel K Spadola A Yuan E Kosek J Jiang L Hod E Li K Murty VV Schupf N Vilain E Morris M Haghighi F Tycko B 《Nature genetics》2008,40(7):904-908
Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when genomic DNAs were predigested with the methylation-sensitive restriction enzyme HpaII. Using independent assays, we confirmed ASM at 16 SNP-tagged loci distributed across various chromosomes. At 12 of these loci (75%), the ASM tracked strongly with the sequence of adjacent SNPs. Further analysis showed allele-specific mRNA expression at two loci from this methylation-based screen--the vanin and CYP2A6-CYP2A7 gene clusters--both implicated in traits of medical importance. This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes. 相似文献
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Many sequence variants affecting diversity of adult human height 总被引:1,自引:0,他引:1
Gudbjartsson DF Walters GB Thorleifsson G Stefansson H Halldorsson BV Zusmanovich P Sulem P Thorlacius S Gylfason A Steinberg S Helgadottir A Ingason A Steinthorsdottir V Olafsdottir EJ Olafsdottir GH Jonsson T Borch-Johnsen K Hansen T Andersen G Jorgensen T Pedersen O Aben KK Witjes JA Swinkels DW den Heijer M Franke B Verbeek AL Becker DM Yanek LR Becker LC Tryggvadottir L Rafnar T Gulcher J Kiemeney LA Kong A Thorsteinsdottir U Stefansson K 《Nature genetics》2008,40(5):609-615
Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene. 相似文献
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Humans show great variation in phenotypic traits such as height, eye color and susceptibility to disease. Genomic DNA sequence differences among individuals are responsible for the inherited components of these complex traits. Reports suggest that intermediate and large-scale DNA copy number and structural variations are prevalent enough to be an important source of genetic variation between individuals. Because association studies to identify genomic loci associated with particular phenotypic traits have focused primarily on genotyping SNPs, it is important to determine whether common structural polymorphisms are in linkage disequilibrium with common SNPs, and thus can be assessed indirectly in SNP-based studies. Here we examine 100 deletion polymorphisms ranging from 70 bp to 7 kb. We show that common deletions and SNPs ascertained with similar criteria have essentially the same distribution of linkage disequilibrium with surrounding SNPs, indicating that these polymorphisms may share evolutionary history and that most deletion polymorphisms are effectively assayed by proxy in SNP-based association studies. 相似文献
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Mehrabian M Allayee H Stockton J Lum PY Drake TA Castellani LW Suh M Armour C Edwards S Lamb J Lusis AJ Schadt EE 《Nature genetics》2005,37(11):1224-1233
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Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse 总被引:24,自引:0,他引:24
Lindblad-Toh K Winchester E Daly MJ Wang DG Hirschhorn JN Laviolette JP Ardlie K Reich DE Robinson E Sklar P Shah N Thomas D Fan JB Gingeras T Warrington J Patil N Hudson TJ Lander ES 《Nature genetics》2000,24(4):381-386
Single-nucleotide polymorphisms (SNPs) have been the focus of much attention in human genetics because they are extremely abundant and well-suited for automated large-scale genotyping. Human SNPs, however, are less informative than other types of genetic markers (such as simple-sequence length polymorphisms or microsatellites) and thus more loci are required for mapping traits. SNPs offer similar advantages for experimental genetic organisms such as the mouse, but they entail no loss of informativeness because bi-allelic markers are fully informative in analysing crosses between inbred strains. Here we report a large-scale analysis of SNPs in the mouse genome. We characterized the rate of nucleotide polymorphism in eight mouse strains and identified a collection of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the mouse genome, providing a first-generation SNP map of the mouse. We have also developed a multiplex genotyping procedure by which a genome scan can be performed with only six genotyping reactions per animal. 相似文献
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The developmental dynamics of the maize leaf transcriptome 总被引:5,自引:0,他引:5
Li P Ponnala L Gandotra N Wang L Si Y Tausta SL Kebrom TH Provart N Patel R Myers CR Reidel EJ Turgeon R Liu P Sun Q Nelson T Brutnell TP 《Nature genetics》2010,42(12):1060-1067
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Wen W Cho YS Zheng W Dorajoo R Kato N Qi L Chen CH Delahanty RJ Okada Y Tabara Y Gu D Zhu D Haiman CA Mo Z Gao YT Saw SM Go MJ Takeuchi F Chang LC Kokubo Y Liang J Hao M Le Marchand L Zhang Y Hu Y Wong TY Long J Han BG Kubo M Yamamoto K Su MH Miki T Henderson BE Song H Tan A He J Ng DP Cai Q Tsunoda T Tsai FJ Iwai N Chen GK Shi J Xu J Sim X Xiang YB Maeda S Ong RT Li C Nakamura Y Aung T Kamatani N Liu JJ Lu W Yokota M Seielstad M 《Nature genetics》2012,44(3):307-311
Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10(-8)), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10(-7). Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. 相似文献
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Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease 总被引:22,自引:0,他引:22
Hubner N Wallace CA Zimdahl H Petretto E Schulz H Maciver F Mueller M Hummel O Monti J Zidek V Musilova A Kren V Causton H Game L Born G Schmidt S Müller A Cook SA Kurtz TW Whittaker J Pravenec M Aitman TJ 《Nature genetics》2005,37(3):243-253
Integration of genome-wide expression profiling with linkage analysis is a new approach to identifying genes underlying complex traits. We applied this approach to the regulation of gene expression in the BXH/HXB panel of rat recombinant inbred strains, one of the largest available rodent recombinant inbred panels and a leading resource for genetic analysis of the highly prevalent metabolic syndrome. In two tissues important to the pathogenesis of the metabolic syndrome, we mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome. Many of the most highly linked expression quantitative trait loci are regulated in cis, are inherited essentially as monogenic traits and are good candidate genes for previously mapped physiological quantitative trait loci in the rat. By comparative mapping we generated a data set of 73 candidate genes for hypertension that merit testing in human populations. Mining of this publicly available data set is expected to lead to new insights into the genes and regulatory pathways underlying the extensive range of metabolic and cardiovascular disease phenotypes that segregate in these recombinant inbred strains. 相似文献
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Small KS Hedman AK Grundberg E Nica AC Thorleifsson G Kong A Thorsteindottir U Shin SY Richards HB;GIANT Consortium;MAGIC Investigators;DIAGRAM Consortium Soranzo N Ahmadi KR Lindgren CM Stefansson K Dermitzakis ET Deloukas P Spector TD McCarthy MI;MuTHER Consortium 《Nature genetics》2011,43(6):561-564
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Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. 总被引:43,自引:0,他引:43
M K Halushka J B Fan K Bentley L Hsie N Shen A Weder R Cooper R Lipshutz A Chakravarti 《Nature genetics》1999,22(3):239-247
Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences. 相似文献
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We performed a whole-genome association analysis of lung tumor susceptibility using dense SNP maps ( approximately 1 SNP per 20 kb) in inbred mice. We reproduced the pulmonary adenoma susceptibility 1 (Pas1) locus identified in previous linkage studies and further narrowed this quantitative trait locus (QTL) to a region of less than 0.5 Mb in which at least two genes, Kras2 (Kirsten rat sarcoma oncogene 2) and Casc1 (cancer susceptibility candidate 1; also known as Las1), are strong candidates. Casc1 knockout mouse tumor bioassays showed that Casc1-deficient mice were susceptible to chemical induction of lung tumors. We also found three more genetic loci for lung adenoma development. Analysis of one of these candidate loci identified a previously uncharacterized gene Lasc1, bearing a nonsynonymous substitution (D102E). We found that the Lasc1 Glu102 allele preferentially promotes lung tumor cell growth. Our findings demonstrate the prospects for using dense SNP maps in laboratory mice to refine previous QTL regions and identify genetic determinants of complex traits. 相似文献
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Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration 总被引:12,自引:0,他引:12
Maller J George S Purcell S Fagerness J Altshuler D Daly MJ Seddon JM 《Nature genetics》2006,38(9):1055-1059
Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed purely additive accumulation of risk from alleles at these genes. We found no differences in association of these loci with major phenotypic categories of advanced AMD. Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population. 相似文献
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Galarneau G Palmer CD Sankaran VG Orkin SH Hirschhorn JN Lettre G 《Nature genetics》2010,42(12):1049-1051
We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production. 相似文献
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Riedelsheimer C Czedik-Eysenberg A Grieder C Lisec J Technow F Sulpice R Altmann T Stitt M Willmitzer L Melchinger AE 《Nature genetics》2012,44(2):217-220
Maize is both an exciting model organism in plant genetics and also the most important crop worldwide for food, animal feed and bioenergy production. Recent genome-wide association and metabolic profiling studies aimed to resolve quantitative traits to their causal genetic loci and key metabolic regulators. Here we present a complementary approach that exploits large-scale genomic and metabolic information to predict complex, highly polygenic traits in hybrid testcrosses. We crossed 285 diverse Dent inbred lines from worldwide sources with two testers and predicted their combining abilities for seven biomass- and bioenergy-related traits using 56,110 SNPs and 130 metabolites. Whole-genome and metabolic prediction models were built by fitting effects for all SNPs or metabolites. Prediction accuracies ranged from 0.72 to 0.81 for SNPs and from 0.60 to 0.80 for metabolites, allowing a reliable screening of large collections of diverse inbred lines for their potential to create superior hybrids. 相似文献