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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Elia J Glessner JT Wang K Takahashi N Shtir CJ Hadley D Sleiman PM Zhang H Kim CE Robison R Lyon GJ Flory JH Bradfield JP Imielinski M Hou C Frackelton EC Chiavacci RM Sakurai T Rabin C Middleton FA Thomas KA Garris M Mentch F Freitag CM Steinhausen HC Todorov AA Reif A Rothenberger A Franke B Mick EO Roeyers H Buitelaar J Lesch KP Banaschewski T Ebstein RP Mulas F Oades RD Sergeant J Sonuga-Barke E Renner TJ Romanos M Romanos J Warnke A Walitza S Meyer J Pálmason H Seitz C Loo SK Smalley SL 《Nature genetics》2012,44(1):78-84
Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts. 相似文献
992.
993.
A new study reports comparative genomic analysis of 52 geographically diverse strains of Chlamydia trachomatis. The authors reconstruct a genome-wide phylogeny of the species and report extensive genome-wide recombination across multiple lineages of this intracellular bacterial pathogen. 相似文献
994.
995.
Anderson BH Kasher PR Mayer J Szynkiewicz M Jenkinson EM Bhaskar SS Urquhart JE Daly SB Dickerson JE O'Sullivan J Leibundgut EO Muter J Abdel-Salem GM Babul-Hirji R Baxter P Berger A Bonafé L Brunstom-Hernandez JE Buckard JA Chitayat D Chong WK Cordelli DM Ferreira P Fluss J Forrest EH Franzoni E Garone C Hammans SR Houge G Hughes I Jacquemont S Jeannet PY Jefferson RJ Kumar R Kutschke G Lundberg S Lourenço CM Mehta R Naidu S Nischal KK Nunes L Ounap K Philippart M Prabhakar P Risen SR 《Nature genetics》2012,44(3):338-342
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity. 相似文献
996.
Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs 总被引:1,自引:0,他引:1
Lee SH DeCandia TR Ripke S Yang J;Schizophrenia Psychiatric Genome-Wide Association Study Consortium 《Nature genetics》2012,44(3):247-250
Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases. 相似文献
997.
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
998.
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
999.
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
1000.
Golubchik T Brueggemann AB Street T Gertz RE Spencer CC Ho T Giannoulatou E Link-Gelles R Harding RM Beall B Peto TE Moore MR Donnelly P Crook DW Bowden R 《Nature genetics》2012,44(3):352-355
Streptococcus pneumoniae ('pneumococcus') causes an estimated 14.5 million cases of serious disease and 826,000 deaths annually in children under 5 years of age(1). The highly effective introduction of the PCV7 pneumococcal vaccine in 2000 in the United States(2,3) provided an unprecedented opportunity to investigate the response of an important pathogen to widespread, vaccine-induced selective pressure. Here, we use array-based sequencing of 62 isolates from a US national monitoring program to study five independent instances of vaccine escape recombination(4), showing the simultaneous transfer of multiple and often large (up to at least 44 kb) DNA fragments. We show that one such new strain quickly became established, spreading from east to west across the United States. These observations clarify the roles of recombination and selection in the population genomics of pneumococcus and provide proof of principle of the considerable value of combining genomic and epidemiological information in the surveillance and enhanced understanding of infectious diseases. 相似文献