Abstract:
:We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Bottini N,Musumeci L,Alonso A,Rahmouni S,Nika K,Rostamkhani M,MacMurray J,Meloni GF,Lucarelli P,Pellecchia M,Eisenbarth GS,Comings D,Mustelin Tdoi
10.1038/ng1323keywords:
subject
Has Abstractpub_date
2004-04-01 00:00:00pages
337-8issue
4eissn
1061-4036issn
1546-1718pii
ng1323journal_volume
36pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.190
更新日期:2008-08-01 00:00:00
abstract::Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS an...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng2099
更新日期:2007-08-01 00:00:00
abstract::Variation of flowering time is found in the natural populations of many plant species. The underlying genetic variation, mostly of a quantitative nature, is presumed to reflect adaptations to different environments contributing to reproductive success. Analysis of natural variation for flowering time in Arabidopsis th...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng767
更新日期:2001-12-01 00:00:00
abstract::We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expressio...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.129
更新日期:2008-05-01 00:00:00
abstract::We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.254
更新日期:2008-12-01 00:00:00
abstract::Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wid...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.922
更新日期:2011-09-11 00:00:00
abstract::We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involve...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0223-8
更新日期:2018-11-01 00:00:00
abstract::Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encodi...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0694-136
更新日期:1994-06-01 00:00:00
abstract::Although nearly half of human melanomas harbor oncogenic BRAF(V600E) mutations, the genetic events that cooperate with these mutations to drive melanogenesis are still largely unknown. Here we show that Sleeping Beauty (SB) transposon-mediated mutagenesis drives melanoma progression in Braf(V600E) mutant mice and iden...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3275
更新日期:2015-05-01 00:00:00
abstract::Using transgenic mice expressing human cystatin C (encoded by CST3), we show that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein (APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substan...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2007.29
更新日期:2007-12-01 00:00:00
abstract::Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the mig...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2259
更新日期:2012-05-13 00:00:00
abstract::R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, th...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1907
更新日期:2006-11-01 00:00:00
abstract::Genomic and proteomic approaches can provide hypotheses concerning function for the large number of genes predicted from genome sequences. Because of the artificial nature of the assays, however, the information from these high-throughput approaches should be considered with caution. Although it is possible that more ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng776
更新日期:2001-12-01 00:00:00
abstract::We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin binds and carries O(2...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.574
更新日期:2010-06-01 00:00:00
abstract::Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampli...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1237
更新日期:2003-10-01 00:00:00
abstract::Genome-wide association studies with SNP markers are expected to allow identification of genes that underlie complex disorders. Hundreds of thousands of SNP markers will be required for comprehensive genome-wide association studies. The development of microarray-based methods for SNP genotyping on this scale remains a...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1558
更新日期:2005-06-01 00:00:00
abstract::Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea, produce heat-stable and/or heat-labile enterotoxins and at least 25 different colonization factors that target the intestinal mucosa. The genes encoding the enterotoxins and most of the colonization factors are located on plasmids found acr...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3145
更新日期:2014-12-01 00:00:00
abstract::Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected f...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0897-345
更新日期:1997-08-01 00:00:00
abstract::Here we ask the question "How much information do epigenomic datasets provide about human genomic function?" We consider nine epigenomic features across 115 cell types and measure information about function as a reduction in entropy under a probabilistic evolutionary model fitted to human and nonhuman primate genomes....
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0300-z
更新日期:2019-02-01 00:00:00
abstract::Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2252
更新日期:2012-05-01 00:00:00
abstract::The GM2 gangliosidoses, Tay-Sachs and Sandhoff diseases, are caused by mutations in the HEXA (alpha-subunit) and HEXB (beta-subunit) genes, respectively. Each gene encodes a subunit for the heterodimeric lysosomal enzyme, beta-hexosaminidase A (alpha beta), as well as for the homodimers beta-hexosaminidase B (beta bet...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1196-348
更新日期:1996-11-01 00:00:00
abstract::With access to whole genome sequences for various organisms and imminent completion of the Human Genome Project, the entire process of discovery in molecular and cellular biology is poised to change. Massively parallel measurement strategies promise to revolutionize how we study and ultimately understand the complex b...
journal_title:Nature genetics
pub_type: 杂志文章,评审
doi:10.1038/13783
更新日期:1999-10-01 00:00:00
abstract::A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability. ...
journal_title:Nature genetics
pub_type: 评论,新闻
doi:10.1038/ng0610-478
更新日期:2010-06-01 00:00:00
abstract::Using next-generation sequencing of primary acute myeloid leukemia (AML) specimens, we identified to our knowledge the first unifying genetic network common to the two subgroups of KMT2A (MLL)-rearranged leukemia, namely having MLL fusions or partial tandem duplications. Within this network, we experimentally confirme...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3371
更新日期:2015-09-01 00:00:00
abstract::MicroRNAs (miRNAs) are key regulators of gene expression in animals and plants. Studies in a variety of model organisms show that miRNAs modulate developmental processes. To our knowledge, the only hereditary condition known to be caused by a miRNA is a form of adult-onset non-syndromic deafness, and no miRNA mutation...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.915
更新日期:2011-09-04 00:00:00
abstract::PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1415
更新日期:2004-10-01 00:00:00
abstract::Congenital disorders of glycosylation (CDG) comprise a rapidly growing group of inherited disorders in which glycosylation of glycoproteins is defective due to mutations in genes required for the assembly of lipid-linked oligosaccharides, their transfer to nascent glycoproteins (CDG-I) or the processing of protein-bou...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0501-73
更新日期:2001-05-01 00:00:00
abstract::The approach to annotating a genome critically affects the number and accuracy of genes identified in the genome sequence. Genome annotation based on stringent gene identification is prone to underestimate the complement of genes encoded in a genome. In contrast, over-prediction of putative genes followed by exhaustiv...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/85922
更新日期:2001-03-01 00:00:00
abstract::The fundamental aim of genetics is to understand how an organism's phenotype is determined by its genotype, and implicit in this is predicting how changes in DNA sequence alter phenotypes. A single network covering all the genes of an organism might guide such predictions down to the level of individual cells and tiss...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2007.70
更新日期:2008-02-01 00:00:00
abstract::We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptoti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.103
更新日期:2008-04-01 00:00:00