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191.
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
192.
Kalay E Yigit G Aslan Y Brown KE Pohl E Bicknell LS Kayserili H Li Y Tüysüz B Nürnberg G Kiess W Koegl M Baessmann I Buruk K Toraman B Kayipmaz S Kul S Ikbal M Turner DJ Taylor MS Aerts J Scott C Milstein K Dollfus H Wieczorek D Brunner HG Hurles M Jackson AP Rauch A Nürnberg P Karagüzel A Wollnik B 《Nature genetics》2011,43(1):23-26
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. 相似文献
193.
Wright FA Strug LJ Doshi VK Commander CW Blackman SM Sun L Berthiaume Y Cutler D Cojocaru A Collaco JM Corey M Dorfman R Goddard K Green D Kent JW Lange EM Lee S Li W Luo J Mayhew GM Naughton KM Pace RG Paré P Rommens JM Sandford A Stonebraker JR Sun W Taylor C Vanscoy LL Zou F Blangero J Zielenski J O'Neal WK Drumm ML Durie PR Knowles MR Cutting GR 《Nature genetics》2011,43(6):539-546
A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder. 相似文献
194.
Sulem P Gudbjartsson DF Walters GB Helgadottir HT Helgason A Gudjonsson SA Zanon C Besenbacher S Bjornsdottir G Magnusson OT Magnusson G Hjartarson E Saemundsdottir J Gylfason A Jonasdottir A Holm H Karason A Rafnar T Stefansson H Andreassen OA Pedersen JH Pack AI de Visser MC Kiemeney LA Geirsson AJ Eyjolfsson GI Olafsson I Kong A Masson G Jonsson H Thorsteinsdottir U Jonsdottir I Stefansson K 《Nature genetics》2011,43(11):1127-1130
We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits. 相似文献
195.
Macgregor S Montgomery GW Liu JZ Zhao ZZ Henders AK Stark M Schmid H Holland EA Duffy DL Zhang M Painter JN Nyholt DR Maskiell JA Jetann J Ferguson M Cust AE Jenkins MA Whiteman DC Olsson H Puig S Bianchi-Scarrà G Hansson J Demenais F Landi MT Dębniak T Mackie R Azizi E Bressac-de Paillerets B Goldstein AM Kanetsky PA Gruis NA Elder DE Newton-Bishop JA Bishop DT Iles MM Helsing P Amos CI Wei Q Wang LE Lee JE Qureshi AA Kefford RF Giles GG Armstrong BK Aitken JF Han J Hopper JL Trent JM Brown KM 《Nature genetics》2011,43(11):1114-1118
We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density. 相似文献
196.
Gui Y Guo G Huang Y Hu X Tang A Gao S Wu R Chen C Li X Zhou L He M Li Z Sun X Jia W Chen J Yang S Zhou F Zhao X Wan S Ye R Liang C Liu Z Huang P Liu C Jiang H Wang Y Zheng H Sun L Liu X Jiang Z Feng D Chen J Wu S Zou J Zhang Z Yang R Zhao J Xu C Yin W Guan Z Ye J Zhang H Li J Kristiansen K Nickerson ML Theodorescu D Li Y Zhang X Li S Wang J Yang H Wang J Cai Z 《Nature genetics》2011,43(9):875-878
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer. 相似文献
197.
Matmati M Jacques P Maelfait J Verheugen E Kool M Sze M Geboes L Louagie E Mc Guire C Vereecke L Chu Y Boon L Staelens S Matthys P Lambrecht BN Schmidt-Supprian M Pasparakis M Elewaut D Beyaert R van Loo G 《Nature genetics》2011,43(9):908-912
A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies. 相似文献
198.
A rare penetrant mutation in CFH confers high risk of age-related macular degeneration 总被引:1,自引:0,他引:1
199.
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters 总被引:5,自引:0,他引:5
200.
Dobbins SE Broderick P Melin B Feychting M Johansen C Andersson U Brännström T Schramm J Olver B Lloyd A Ma YP Hosking FJ Lönn S Ahlbom A Henriksson R Schoemaker MJ Hepworth SJ Hoffmann P Mühleisen TW Nöthen MM Moebus S Eisele L Kosteljanetz M Muir K Swerdlow A Simon M Houlston RS 《Nature genetics》2011,43(9):825-827
To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development. 相似文献