Abstract:
:Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Dumitrescu AM,Liao XH,Abdullah MS,Lado-Abeal J,Majed FA,Moeller LC,Boran G,Schomburg L,Weiss RE,Refetoff Sdoi
10.1038/ng1654keywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
1247-52issue
11eissn
1061-4036issn
1546-1718pii
ng1654journal_volume
37pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::UV-sensitive syndrome (UV(S)S) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma. Despite mild clinical features, cells from individuals with UV(S)S, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER), ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2229
更新日期:2012-05-01 00:00:00
abstract::We are beginning to elucidate transcriptional regulatory networks on a large scale and to understand some of the structural principles of these networks, but the evolutionary mechanisms that form these networks are still mostly unknown. Here we investigate the role of gene duplication in network evolution. Gene duplic...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1340
更新日期:2004-05-01 00:00:00
abstract::N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that abundant 6mA is associated with transcriptionally active genes in ea...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3859
更新日期:2017-06-01 00:00:00
abstract::Comparisons of chromosome X and the autosomes can illuminate differences in the histories of males and females as well as shed light on the forces of natural selection. We compared the patterns of variation in these parts of the genome using two datasets that we assembled for this study that are both genomic in scale....
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.303
更新日期:2009-01-01 00:00:00
abstract::Methylation of DNA at the dinucleotide CpG is essential for mammalian development and is correlated with stable transcriptional silencing. This transcriptional silencing has recently been linked at a molecular level to histone deacetylation through the demonstration of a physical association between histone deacetylas...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/12664
更新日期:1999-09-01 00:00:00
abstract::We report that mutation in the gene for plectin, a cytoskeleton-membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, s...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0896-450
更新日期:1996-08-01 00:00:00
abstract::Animal development is an extremely robust process resulting in stereotyped outcomes. Canalization is a design principle wherein developmental pathways are stabilized to increase phenotypic reproducibility. Recent revelations into microRNA (miRNA) function suggest that miRNAs act as key players in canalizing genetic pr...
journal_title:Nature genetics
pub_type: 杂志文章,评审
doi:10.1038/ng1803
更新日期:2006-06-01 00:00:00
abstract::The maintenance of chromosome termini, or telomeres, requires the action of the enzyme telomerase, as conventional DNA polymerases cannot fully replicate the ends of linear molecules. Telomerase is expressed and telomere length is maintained in human germ cells and the great majority of primary human tumours. However,...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1297-498
更新日期:1997-12-01 00:00:00
abstract::Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is confe...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0297-201
更新日期:1997-02-01 00:00:00
abstract::We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale w...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/s41588-018-0154-4
更新日期:2018-07-01 00:00:00
abstract::The homeodomain protein IPF1 (also known as IDX1, STF1 and PDX1; see Methods) is critical for development of the pancreas in mice and is a key factor for the regulation of the insulin gene in the beta-cells of the endocrine pancreas. Targeted disruption of the Ipf1 gene encoding IPF1 in transgenic mice results in a fa...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0197-106
更新日期:1997-01-01 00:00:00
abstract::Micro RNAs are a large family of noncoding RNAs of 21-22 nucleotides whose functions are generally unknown. Here a large subset of Drosophila micro RNAs is shown to be perfectly complementary to several classes of sequence motif previously demonstrated to mediate negative post-transcriptional regulation. These finding...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng865
更新日期:2002-04-01 00:00:00
abstract::Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963...
journal_title:Nature genetics
pub_type: 信件
doi:10.1038/ng.2882
更新日期:2014-03-01 00:00:00
abstract::In the version of this article initially published, '+' and '-' labels were missing from the graph keys at the bottom of Fig. 8d. The error has been corrected in the HTML and PDF versions of the article. ...
journal_title:Nature genetics
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41588-018-0341-3
更新日期:2019-02-01 00:00:00
abstract::To investigate the role of type X collagen in skeletal development, we have generated type X collagen-null mice. Surprisingly, mice without type X collagen were viable and fertile and had no gross abnormalities in long bone growth or development. No differences were detected between the type X collagen-null mice and c...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1094-129
更新日期:1994-10-01 00:00:00
abstract::Crosstalk between signaling pathways is crucial for the generation of complex and varied transcriptional networks. Antagonism between the EGF-receptor (EGFR) and Notch pathways in particular is well documented, although the underlying mechanism is poorly understood. The global corepressor Groucho (Gro) and its transdu...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1486
更新日期:2005-01-01 00:00:00
abstract::Recent research has uncovered an important role for de novo variation in neurodevelopmental disorders. Using aggregated data from 9,246 families with autism spectrum disorder, intellectual disability, or developmental delay, we found that ∼1/3 of de novo variants are independently present as standing variation in the ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3789
更新日期:2017-04-01 00:00:00
abstract::We have carried out automated extraction of explicit and implicit biomedical knowledge from publicly available gene and text databases to create a gene-to-gene co-citation network for 13,712 named human genes by automated analysis of titles and abstracts in over 10 million MEDLINE records. The associations between gen...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0501-21
更新日期:2001-05-01 00:00:00
abstract::The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor supp...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3817
更新日期:2017-05-01 00:00:00
abstract::Uterine leiomyomata (fibroids) are common and clinically important tumors, but little is known about their etiology and pathogenesis. We previously mapped a gene that predisposes to multiple fibroids, cutaneous leiomyomata and renal cell carcinoma to chromosome 1q42.3-q43 (refs 4-6). Here we show, through a combinatio...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng849
更新日期:2002-04-01 00:00:00
abstract::The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1104-1133
更新日期:2004-11-01 00:00:00
abstract::Thomsen's disease (autosomal dominant myotonia congenita) has recently been linked to chromosome 7q35 in the region of the human skeletal muscle chloride channel gene (HUMCLC). Single strand conformation polymorphism analysis (SSCP) was used to screen DNA from members of four unrelated pedigrees with this disorder for...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0493-305
更新日期:1993-04-01 00:00:00
abstract::Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 ad...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.686
更新日期:2010-11-01 00:00:00
abstract::We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.807
更新日期:2011-05-01 00:00:00
abstract::Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in a copper-effluxing ATPase, designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a fe...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0696-219
更新日期:1996-06-01 00:00:00
abstract::Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increas...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/76088
更新日期:2000-06-01 00:00:00
abstract::Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma. The extent of skeletal inv...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng844
更新日期:2002-03-01 00:00:00
abstract::The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo in a p5...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng714
更新日期:2001-09-01 00:00:00
abstract::Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1152
更新日期:2003-05-01 00:00:00
abstract::Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,10...
journal_title:Nature genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/s41588-020-0636-z
更新日期:2020-06-01 00:00:00