Abstract:
:The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Shackleton S,Lloyd DJ,Jackson SN,Evans R,Niermeijer MF,Singh BM,Schmidt H,Brabant G,Kumar S,Durrington PN,Gregory S,O'Rahilly S,Trembath RCdoi
10.1038/72807keywords:
subject
Has Abstractpub_date
2000-02-01 00:00:00pages
153-6issue
2eissn
1061-4036issn
1546-1718journal_volume
24pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Genetic integrity is crucial to normal cell function, and mutations in genes required for DNA replication and repair underlie various forms of genetic instability and disease, including cancer. One structural feature of intact genomes is runs of homopolymeric dC/dG. Here we describe an unusual mutator phenotype in Cae...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng928
更新日期:2002-08-01 00:00:00
abstract::Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1357
更新日期:2004-06-01 00:00:00
abstract::Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal p...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng2082
更新日期:2007-09-01 00:00:00
abstract::Densely methylated DNA associates with transcriptionally repressive chromatin characterized by the presence of underacetylated histones. Recently, these two epigenetic processes have been dynamically linked. The methyl-CpG-binding protein MeCP2 appears to reside in a complex with histone deacetylase activity. MeCP2 ca...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/5047
更新日期:1999-01-01 00:00:00
abstract::Intestinal microbiota is known to be important in health and disease. Its composition is influenced by both environmental and host factors. Few large-scale studies have evaluated the association between host genetic variation and the composition of microbiota. We recruited a cohort of 1,561 healthy individuals, of who...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3693
更新日期:2016-11-01 00:00:00
abstract::The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AG...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.517
更新日期:2010-02-01 00:00:00
abstract::Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive disorder characterized by slowly progressing contractures, wasting of skeletal muscle and cardiomyopathy. Heart block is a frequent cause of death. The disease gene has been mapped to distal Xq28. Among many genes in this region, we selected eight trans...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1294-323
更新日期:1994-12-01 00:00:00
abstract::Jackson-Weiss syndrome is an autosomal dominant condition characterized by craniosynostosis, foot anomalies and great phenotypic variability. Recently mutations in fibroblast growth factor receptor 2 (FGFR2) have been found in patients with another craniosynostotic syndrome, Crouzon syndrome. FGFR2 is a member of the ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1194-275
更新日期:1994-11-01 00:00:00
abstract::Domestication of cereal crops, such as maize, wheat and rice, had a profound influence on agriculture and the establishment of human civilizations. One major improvement was an increase in seed number per inflorescence, which enhanced yield and simplified harvesting and storage. The ancestor of maize, teosinte, makes ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2534
更新日期:2013-03-01 00:00:00
abstract::A CRISPR screen conducted in a CD4+ T cell leukemia line has identified host factors required for HIV infection but dispensable for cellular survival. The results highlight sulfation on the HIV co-receptor CCR5 and cellular aggregation as potential targets for therapeutic intervention. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3777
更新日期:2017-01-31 00:00:00
abstract::Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protei...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.271
更新日期:2009-01-01 00:00:00
abstract::The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1022
更新日期:2002-12-01 00:00:00
abstract::It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by sear...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1294-380
更新日期:1994-12-01 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::Plasma iron circulates bound to transferrin (Trf), which solubilizes the ferric ion and attenuates its reactivity. Diferric Trf interacts with cell-surface Trf receptor (Trfr) to undergo receptor-mediated endocytosis into specialized endosomes. Endosomal acidification leads to iron release, and iron is transported out...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/7727
更新日期:1999-04-01 00:00:00
abstract::To shed light on the peopling of South Asia and the origins of the morphological adaptations found there, we analyzed whole-genome sequences from 10 Andamanese individuals and compared them with sequences for 60 individuals from mainland Indian populations with different ethnic histories and with publicly available da...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3621
更新日期:2016-09-01 00:00:00
abstract::Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] famil...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1985
更新日期:2007-03-01 00:00:00
abstract::Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis, but the molecular hallmarks of tumor hypoxia remain poorly defined. To fill this gap, we quantified hypoxia in 8,006 tumors across 19 tumor types. In ten tumo...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0318-2
更新日期:2019-02-01 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::Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation into clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator gene CFTR have empirical evidence that they cause cystic fibrosis. To address this ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2745
更新日期:2013-10-01 00:00:00
abstract::Loci discovered by genome-wide association studies predominantly map outside protein-coding genes. The interpretation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0322-6
更新日期:2019-02-01 00:00:00
abstract::Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum In...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1201-365
更新日期:2001-12-01 00:00:00
abstract::The shift from outcrossing to selfing is common in flowering plants, but the genomic consequences and the speed at which they emerge remain poorly understood. An excellent model for understanding the evolution of self fertilization is provided by Capsella rubella, which became self compatible <200,000 years ago. We re...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2669
更新日期:2013-07-01 00:00:00
abstract::How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprisi...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3348
更新日期:2015-07-01 00:00:00
abstract::Copy number variations (CNVs) often include noncoding sequences and putative enhancers, but how these rearrangements induce disease is poorly understood. Here we investigate CNVs involving the regulatory landscape of IHH (encoding Indian hedgehog), which cause multiple, highly localized phenotypes including craniosyno...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3939
更新日期:2017-10-01 00:00:00
abstract::Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as v...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng925
更新日期:2002-08-01 00:00:00
abstract::Altering cytosine methylation by genetic means leads to a variety of developmental defects in mice, plants and fungi. Deregulation of cytosine methylation also has a role in human carcinogenesis. In some cases, these defects have been tied to the inheritance of epigenetic alterations (such as chromatin imprints and DN...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/8803
更新日期:1999-05-01 00:00:00
abstract::A genome-wide association scan of approximately 6.6 million genotyped or imputed variants in 882 Sardinian individuals with multiple sclerosis (cases) and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (rs9657904, overall P = 1.60 x 10(-10),...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.584
更新日期:2010-06-01 00:00:00
abstract::Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertrigl...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2007.24
更新日期:2007-12-01 00:00:00
abstract::CHARGE syndrome is a common cause of congenital anomalies affecting several tissues in a nonrandom fashion. We report a 2.3-Mb de novo overlapping microdeletion on chromosome 8q12 identified by array comparative genomic hybridization in two individuals with CHARGE syndrome. Sequence analysis of genes located in this r...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1407
更新日期:2004-09-01 00:00:00