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排序方式: 共有279条查询结果,搜索用时 31 毫秒
221.
Wegmann D Kessner DE Veeramah KR Mathias RA Nicolae DL Yanek LR Sun YV Torgerson DG Rafaels N Mosley T Becker LC Ruczinski I Beaty TH Kardia SL Meyers DA Barnes KC Becker DM Freimer NB Novembre J 《Nature genetics》2011,43(9):847-853
Studies of recombination and how it varies depend crucially on accurate recombination maps. We propose a new approach for constructing high-resolution maps of relative recombination rates based on the observation of ancestry switch points among admixed individuals. We show the utility of this approach using simulations and by applying it to SNP genotype data from a sample of 2,565 African Americans and 299 African Caribbeans and detecting several hundred thousand recombination events. Comparison of the inferred map with high-resolution maps from non-admixed populations provides evidence of fine-scale differentiation in recombination rates between populations. Overall, the admixed map is well predicted by the average proportion of admixture and the recombination rate estimates from the source populations. The exceptions to this are in areas surrounding known large chromosomal structural variants, specifically inversions. These results suggest that outside of structurally variable regions, admixture does not substantially disrupt the factors controlling recombination rates in humans. 相似文献
222.
O'Donovan MC Craddock N Norton N Williams H Peirce T Moskvina V Nikolov I Hamshere M Carroll L Georgieva L Dwyer S Holmans P Marchini JL Spencer CC Howie B Leung HT Hartmann AM Möller HJ Morris DW Shi Y Feng G Hoffmann P Propping P Vasilescu C Maier W Rietschel M Zammit S Schumacher J Quinn EM Schulze TG Williams NM Giegling I Iwata N Ikeda M Darvasi A Shifman S He L Duan J Sanders AR Levinson DF Gejman PV Cichon S Nöthen MM Gill M Corvin A Rujescu D Kirov G Owen MJ Buccola NG Mowry BJ 《Nature genetics》2008,40(9):1053-1055
We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)). 相似文献
223.
Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
224.
Leitch CC Zaghloul NA Davis EE Stoetzel C Diaz-Font A Rix S Alfadhel M Al-Fadhel M Lewis RA Eyaid W Banin E Dollfus H Beales PL Badano JL Katsanis N 《Nature genetics》2008,40(4):443-448
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous, neonatally lethal malformation and the most common form of syndromic neural tube defect (NTD). To date, several MKS-associated genes have been identified whose protein products affect ciliary function. Here we show that mutations in MKS1, MKS3 and CEP290 (also known as NPHP6) either can cause Bardet-Biedl syndrome (BBS) or may have a potential epistatic effect on mutations in known BBS-associated loci. Five of six families with both MKS1 and BBS mutations manifested seizures, a feature that is not a typical component of either syndrome. Functional studies in zebrafish showed that mks1 is necessary for gastrulation movements and that it interacts genetically with known bbs genes. Similarly, we found two families with missense or splice mutations in MKS3, in one of which the affected individual also bears a homozygous nonsense mutation in CEP290 that is likely to truncate the C terminus of the protein. These data extend the genetic stratification of ciliopathies and suggest that BBS and MKS, although distinct clinically, are allelic forms of the same molecular spectrum. 相似文献
225.
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis 总被引:1,自引:0,他引:1
Khor CC Chapman SJ Vannberg FO Dunne A Murphy C Ling EY Frodsham AJ Walley AJ Kyrieleis O Khan A Aucan C Segal S Moore CE Knox K Campbell SJ Lienhardt C Scott A Aaby P Sow OY Grignani RT Sillah J Sirugo G Peshu N Williams TN Maitland K Davies RJ Kwiatkowski DP Day NP Yala D Crook DW Marsh K Berkley JA O'Neill LA Hill AV 《Nature genetics》2007,39(4):523-528
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction. 相似文献
226.
Common variants in WFS1 confer risk of type 2 diabetes 总被引:10,自引:0,他引:10
Sandhu MS Weedon MN Fawcett KA Wasson J Debenham SL Daly A Lango H Frayling TM Neumann RJ Sherva R Blech I Pharoah PD Palmer CN Kimber C Tavendale R Morris AD McCarthy MI Walker M Hitman G Glaser B Permutt MA Hattersley AT Wareham NJ Barroso I 《Nature genetics》2007,39(8):951-953
We studied genes involved in pancreatic beta cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with diabetes risk. Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes. 相似文献
227.
Stoetzel C Laurier V Davis EE Muller J Rix S Badano JL Leitch CC Salem N Chouery E Corbani S Jalk N Vicaire S Sarda P Hamel C Lacombe D Holder M Odent S Holder S Brooks AS Elcioglu NH Silva ED Da Silva E Rossillion B Sigaudy S de Ravel TJ Lewis RA Leheup B Verloes A Amati-Bonneau P Mégarbané A Poch O Bonneau D Beales PL Mandel JL Katsanis N Dollfus H 《Nature genetics》2006,38(5):521-524
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants. 相似文献
228.
This comparative study explores the use of the Cohort Component Method (CCM) to produce national level population estimates. This method is used annually to calculate mid-year population estimates for England and Wales by the Office for National Statistics (ONS). Initially the article considers recent population change in England and Wales, with particular emphasis on the growing importance and challenges faced by migration estimation. Comparisons are then made between how population estimates are produced in England and Wales and other countries, with a particular focus on differences in the way the CCM is applied. Recent changes in methods used to estimate population are then reviewed along with a discussion of alternative approaches such as those described in academic literature. 相似文献
229.
Yali Si Fei Xu Jie Wei Lin Zhang Nicholas Murray Rui Yang Keping Ma Peng Gong 《科学通报(英文版)》2021,(10):955-957
The East Asian-Australasian Flyway (EAAF) is the most threatened flyway worldwide, encompassing the greatest number of threatened migratory bird species of all ... 相似文献
230.