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排序方式: 共有621条查询结果,搜索用时 687 毫秒
141.
Allen M Heinzmann A Noguchi E Abecasis G Broxholme J Ponting CP Bhattacharyya S Tinsley J Zhang Y Holt R Jones EY Lench N Carey A Jones H Dickens NJ Dimon C Nicholls R Baker C Xue L Townsend E Kabesch M Weiland SK Carr D von Mutius E Adcock IM Barnes PJ Lathrop GM Edwards M Moffatt MF Cookson WO 《Nature genetics》2003,35(3):258-263
Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy. 相似文献
142.
Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss 总被引:20,自引:0,他引:20
Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23(753A) allele causes in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors is a primary determinant of AHL in mice. 相似文献
143.
Aebischer NJ Baker SE Johnson PJ Macdonald DW Reynolds JC 《Nature》2003,423(6938):400; discussion 400
144.
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146.
Karlsson EK Baranowska I Wade CM Salmon Hillbertz NH Zody MC Anderson N Biagi TM Patterson N Pielberg GR Kulbokas EJ Comstock KE Keller ET Mesirov JP von Euler H Kämpe O Hedhammar A Lander ES Andersson G Andersson L Lindblad-Toh K 《Nature genetics》2007,39(11):1321-1328
With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with approximately 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only approximately 20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of approximately 100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health. 相似文献
147.
Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians. 相似文献
148.
He XC Yin T Grindley JC Tian Q Sato T Tao WA Dirisina R Porter-Westpfahl KS Hembree M Johnson T Wiedemann LM Barrett TA Hood L Wu H Li L 《Nature genetics》2007,39(2):189-198
Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTEN-deficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin. Akt phosphorylates beta-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin. 相似文献
149.
Manning AK Hivert MF Scott RA Grimsby JL Bouatia-Naji N Chen H Rybin D Liu CT Bielak LF Prokopenko I Amin N Barnes D Cadby G Hottenga JJ Ingelsson E Jackson AU Johnson T Kanoni S Ladenvall C Lagou V Lahti J Lecoeur C Liu Y Martinez-Larrad MT Montasser ME Navarro P Perry JR Rasmussen-Torvik LJ Salo P Sattar N Shungin D Strawbridge RJ Tanaka T van Duijn CM An P de Andrade M Andrews JS Aspelund T Atalay M Aulchenko Y Balkau B Bandinelli S Beckmann JS Beilby JP Bellis C Bergman RN Blangero J 《Nature genetics》2012,44(6):659-669
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. 相似文献
150.
Kopp JB Smith MW Nelson GW Johnson RC Freedman BI Bowden DW Oleksyk T McKenzie LM Kajiyama H Ahuja TS Berns JS Briggs W Cho ME Dart RA Kimmel PL Korbet SM Michel DM Mokrzycki MH Schelling JR Simon E Trachtman H Vlahov D Winkler CA 《Nature genetics》2008,40(10):1175-1184
The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans. 相似文献