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排序方式: 共有139条查询结果,搜索用时 31 毫秒
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Maller JB Fagerness JA Reynolds RC Neale BM Daly MJ Seddon JM 《Nature genetics》2007,39(10):1200-1201
The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample. 相似文献
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Anderson BH Kasher PR Mayer J Szynkiewicz M Jenkinson EM Bhaskar SS Urquhart JE Daly SB Dickerson JE O'Sullivan J Leibundgut EO Muter J Abdel-Salem GM Babul-Hirji R Baxter P Berger A Bonafé L Brunstom-Hernandez JE Buckard JA Chitayat D Chong WK Cordelli DM Ferreira P Fluss J Forrest EH Franzoni E Garone C Hammans SR Houge G Hughes I Jacquemont S Jeannet PY Jefferson RJ Kumar R Kutschke G Lundberg S Lourenço CM Mehta R Naidu S Nischal KK Nunes L Ounap K Philippart M Prabhakar P Risen SR 《Nature genetics》2012,44(3):338-342
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity. 相似文献
4.
Extremely low-coverage sequencing and imputation increases power for genome-wide association studies 总被引:1,自引:0,他引:1
Pasaniuc B Rohland N McLaren PJ Garimella K Zaitlen N Li H Gupta N Neale BM Daly MJ Sklar P Sullivan PF Bergen S Moran JL Hultman CM Lichtenstein P Magnusson P Purcell SM Haas DW Liang L Sunyaev S Patterson N de Bakker PI Reich D Price AL 《Nature genetics》2012,44(6):631-635
Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power. 相似文献
5.
Purdue MP Johansson M Zelenika D Toro JR Scelo G Moore LE Prokhortchouk E Wu X Kiemeney LA Gaborieau V Jacobs KB Chow WH Zaridze D Matveev V Lubinski J Trubicka J Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Foretova L Janout V Boffetta P Colt JS Davis FG Schwartz KL Banks RE Selby PJ Harnden P Berg CD Hsing AW Grubb RL Boeing H Vineis P Clavel-Chapelon F Palli D Tumino R Krogh V Panico S Duell EJ Quirós JR Sanchez MJ Navarro C Ardanaz E Dorronsoro M Khaw KT Allen NE 《Nature genetics》2011,43(1):60-65
6.
A rare penetrant mutation in CFH confers high risk of age-related macular degeneration 总被引:1,自引:0,他引:1
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes 总被引:1,自引:0,他引:1
Zeggini E Scott LJ Saxena R Voight BF Marchini JL Hu T de Bakker PI Abecasis GR Almgren P Andersen G Ardlie K Boström KB Bergman RN Bonnycastle LL Borch-Johnsen K Burtt NP Chen H Chines PS Daly MJ Deodhar P Ding CJ Doney AS Duren WL Elliott KS Erdos MR Frayling TM Freathy RM Gianniny L Grallert H Grarup N Groves CJ Guiducci C Hansen T Herder C Hitman GA Hughes TE Isomaa B Jackson AU Jørgensen T Kong A Kubalanza K Kuruvilla FG Kuusisto J Langenberg C Lango H Lauritzen T Li Y Lindgren CM 《Nature genetics》2008,40(5):638-645
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. 相似文献
9.
Vitart V Rudan I Hayward C Gray NK Floyd J Palmer CN Knott SA Kolcic I Polasek O Graessler J Wilson JF Marinaki A Riches PL Shu X Janicijevic B Smolej-Narancic N Gorgoni B Morgan J Campbell S Biloglav Z Barac-Lauc L Pericic M Klaric IM Zgaga L Skaric-Juric T Wild SH Richardson WA Hohenstein P Kimber CH Tenesa A Donnelly LA Fairbanks LD Aringer M McKeigue PM Ralston SH Morris AD Rudan P Hastie ND Campbell H Wright AF 《Nature genetics》2008,40(4):437-442
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes. 相似文献
10.
McCarroll SA Hadnott TN Perry GH Sabeti PC Zody MC Barrett JC Dallaire S Gabriel SB Lee C Daly MJ Altshuler DM;International HapMap Consortium 《Nature genetics》2006,38(1):86-92
The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies. 相似文献