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排序方式: 共有10000条查询结果,搜索用时 234 毫秒
371.
Hüffmeier U Uebe S Ekici AB Bowes J Giardina E Korendowych E Juneblad K Apel M McManus R Ho P Bruce IN Ryan AW Behrens F Lascorz J Böhm B Traupe H Lohmann J Gieger C Wichmann HE Herold C Steffens M Klareskog L Wienker TF Fitzgerald O Alenius GM McHugh NJ Novelli G Burkhardt H Barton A Reis A 《Nature genetics》2010,42(11):996-999
Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. 相似文献
372.
Xue B Mizianty MJ Kurgan L Uversky VN 《Cellular and molecular life sciences : CMLS》2012,69(8):1211-1259
Many proteins and protein regions are disordered in their native, biologically active states. These proteins/regions are abundant
in different organisms and carry out important biological functions that complement the functional repertoire of ordered proteins.
Viruses, with their highly compact genomes, small proteomes, and high adaptability for fast change in their biological and
physical environment utilize many of the advantages of intrinsic disorder. In fact, viral proteins are generally rich in intrinsic
disorder, and intrinsically disordered regions are commonly used by viruses to invade the host organisms, to hijack various
host systems, and to help viruses in accommodation to their hostile habitats and to manage their economic usage of genetic
material. In this review, we focus on the structural peculiarities of HIV-1 proteins, on the abundance of intrinsic disorder
in viral proteins, and on the role of intrinsic disorder in their functions. 相似文献
373.
374.
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376.
Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas 总被引:1,自引:0,他引:1
Wu G Broniscer A McEachron TA Lu C Paugh BS Becksfort J Qu C Ding L Huether R Parker M Zhang J Gajjar A Dyer MA Mullighan CG Gilbertson RJ Mardis ER Wilson RK Downing JR Ellison DW Zhang J Baker SJ;St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project 《Nature genetics》2012,44(3):251-253
To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration. 相似文献
377.
Yang J Ferreira T Morris AP Medland SE;Genetic Investigation of ANthropometric Traits 《Nature genetics》2012,44(4):369-75, S1-3
We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium. 相似文献
378.
Santen GW Aten E Sun Y Almomani R Gilissen C Nielsen M Kant SG Snoeck IN Peeters EA Hilhorst-Hofstee Y Wessels MW den Hollander NS Ruivenkamp CA van Ommen GJ Breuning MH den Dunnen JT van Haeringen A Kriek M 《Nature genetics》2012,44(4):379-380
We identified de novo truncating mutations in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Array-based copy-number variation (CNV) analysis in 2,000 individuals with intellectual disability revealed deletions encompassing ARID1B in 3 subjects with phenotypes partially overlapping that of CSS. Taken together with published data, these results indicate that haploinsufficiency of the ARID1B gene, which encodes an epigenetic modifier of chromatin structure, is an important cause of CSS and is potentially a common cause of intellectual disability and speech impairment. 相似文献
379.
Postel-Vinay S Véron AS Tirode F Pierron G Reynaud S Kovar H Oberlin O Lapouble E Ballet S Lucchesi C Kontny U González-Neira A Picci P Alonso J Patino-Garcia A de Paillerets BB Laud K Dina C Froguel P Clavel-Chapelon F Doz F Michon J Chanock SJ Thomas G Cox DG Delattre O 《Nature genetics》2012,44(3):323-327
Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2. 相似文献
380.
Harakalova M van Harssel JJ Terhal PA van Lieshout S Duran K Renkens I Amor DJ Wilson LC Kirk EP Turner CL Shears D Garcia-Minaur S Lees MM Ross A Venselaar H Vriend G Takanari H Rook MB van der Heyden MA Asselbergs FW Breur HM Swinkels ME Scurr IJ Smithson SF Knoers NV van der Smagt JJ Nijman IJ Kloosterman WP van Haelst MM van Haaften G Cuppen E 《Nature genetics》2012,44(7):793-796
Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome. 相似文献