排序方式: 共有33条查询结果,搜索用时 140 毫秒
1.
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
2.
3.
4.
Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus 总被引:62,自引:0,他引:62
Horikawa Y Oda N Cox NJ Li X Orho-Melander M Hara M Hinokio Y Lindner TH Mashima H Schwarz PE del Bosque-Plata L Horikawa Y Oda Y Yoshiuchi I Colilla S Polonsky KS Wei S Concannon P Iwasaki N Schulze J Baier LJ Bogardus C Groop L Boerwinkle E Hanis CL Bell GI 《Nature genetics》2000,26(2):163-175
Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes. 相似文献
5.
Saliba KJ Martin RE Bröer A Henry RI McCarthy CS Downie MJ Allen RJ Mullin KA McFadden GI Bröer S Kirk K 《Nature》2006,443(7111):582-585
As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte it induces an increase in the permeability of the erythrocyte membrane to a range of low-molecular-mass solutes, including Na+ and K+ (ref. 1). This results in a progressive increase in the concentration of Na+ in the erythrocyte cytosol. The parasite cytosol has a relatively low Na+ concentration and there is therefore a large inward Na+ gradient across the parasite plasma membrane. Here we show that the parasite exploits the Na+ electrochemical gradient to energize the uptake of inorganic phosphate (P(i)), an essential nutrient. P(i) was taken up into the intracellular parasite by a Na+-dependent transporter, with a stoichiometry of 2Na+:1P(i) and with an apparent preference for the monovalent over the divalent form of P(i). A P(i) transporter (PfPiT) belonging to the PiT family was cloned from the parasite and localized to the parasite surface. Expression of PfPiT in Xenopus oocytes resulted in Na+-dependent P(i) uptake with characteristics similar to those observed for P(i) uptake in the parasite. This study provides new insight into the significance of the malaria-parasite-induced alteration of the ionic composition of its host cell. 相似文献
6.
7.
8.
Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver 总被引:57,自引:0,他引:57
Abel ED Peroni O Kim JK Kim YB Boss O Hadro E Minnemann T Shulman GI Kahn BB 《Nature》2001,409(6821):729-733
The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes. 相似文献
9.
10.