Abstract:
:Autosomal dominant optic atrophy (ADOA) is the most prevalent hereditary optic neuropathy resulting in progressive loss of visual acuity, centrocoecal scotoma and bilateral temporal atrophy of the optic nerve with an onset within the first two decades of life. The predominant locus for this disorder (OPA1; MIM 165500) has been mapped to a 1.4-cM interval on chromosome 3q28-q29 flanked by markers D3S3669 and D3S3562 (ref. 3). We established a PAC contig covering the entire OPA1 candidate region of approximately 1 Mb and a sequence skimming approach allowed us to identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases. The gene comprises 28 coding exons and spans more than 40 kb of genomic sequence. Upon sequence analysis, we identified mutations in seven independent families with ADOA. The mutations include missense and nonsense alterations, deletions and insertions, which all segregate with the disease in these families. Because most mutations probably represent null alleles, dominant inheritance of the disease may result from haploinsufficiency of OPA1. OPA1 is widely expressed and is most abundant in the retina. The presence of consensus signal peptide sequences suggests that the product of the gene OPA1 is targeted to mitochondria and may exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Alexander C,Votruba M,Pesch UE,Thiselton DL,Mayer S,Moore A,Rodriguez M,Kellner U,Leo-Kottler B,Auburger G,Bhattacharya SS,Wissinger Bdoi
10.1038/79944keywords:
subject
Has Abstractpub_date
2000-10-01 00:00:00pages
211-5issue
2eissn
1061-4036issn
1546-1718journal_volume
26pub_type
杂志文章相关文献
NATURE GENETICS文献大全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::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::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::Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks. So far, six loci associated with TGCT have been reported. From genome-wide association study (GWAS) analysis of 307,291 SNPs in 986 TGCT cases and 4,946 controls, we selected for follow-up 694 SNPs, whi...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.2635
更新日期:2013-06-01 00:00:00
abstract::The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approa...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/78062
更新日期:2000-08-01 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::To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the abse...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/8751
更新日期:1999-05-01 00:00:00
abstract::Pheromones elicit specific behavioural responses and physiological alterations in recipients of the same species. In mammals, these chemical signals are recognized within the nasal cavity by sensory neurons that express pheromone receptors. In rodents, these receptors are thought to be represented by two large multige...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/79124
更新日期:2000-09-01 00:00:00
abstract::Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predictors of active enha...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-020-0686-2
更新日期:2020-10-01 00:00:00
abstract::The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Han...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0398-266
更新日期:1998-03-01 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::Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal mani...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1805
更新日期:2006-06-01 00:00:00
abstract::Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons wi...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2757
更新日期:2013-10-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3538
更新日期:2016-05-01 00:00:00
abstract::The syndrome of hyperactivity describes behavioural disorders existing mainly in children and characterized by increased levels of motor activity, inattention and impulsivity. Overall the aetiology is poorly understood due to the heterogeneity of the pathology although psychological, biological and social factors acti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1296-471
更新日期:1996-12-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes substantial morbidity. As is typical for many other multifactorial disorders, much of the heritability of SLE remains unknown. We identified a rare autosomal recessive form of SLE, in which autozygome analysis revealed a null mutation in th...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.975
更新日期:2011-10-23 00:00:00
abstract::Structural rearrangements have long been recognized as an important source of genetic variation, with implications in phenotypic diversity and disease, yet their detailed evolutionary dynamics remain elusive. Here we use long-read sequencing to generate end-to-end genome assemblies for 12 strains representing major su...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3847
更新日期:2017-06-01 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 plant circadian clock is a complex network of genes crucial for plant survival. A new study finds that domestication gradually slowed down the circadian clock of tomato via selection on two major genes-one that delayed phasing of the clock with daylight, whereas the other induced a longer period. ...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.3476
更新日期:2016-01-01 00:00:00
abstract::Loss of heterozygosity (LOH) of markers on human chromosome 7q31 is frequently encountered in a variety of human neoplasias, indicating the presence of a tumor-suppressor gene (TSG). By a combination of microcell-fusion and deletion-mapping studies, we previously established that this TSG resides within a critical reg...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/86891
更新日期:2001-04-01 00:00:00
abstract::Transcription is a slow and expensive process: in eukaryotes, approximately 20 nucleotides can be transcribed per second at the expense of at least two ATP molecules per nucleotide. Thus, at least for highly expressed genes, transcription of long introns, which are particularly common in mammals, is costly. Using data...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng940
更新日期:2002-08-01 00:00:00
abstract::Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis ...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.3892
更新日期:2017-07-01 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::Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-fu...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2950
更新日期:2014-05-01 00:00:00
abstract::We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 regio...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.2609
更新日期:2013-06-01 00:00:00
abstract::Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal su...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1168
更新日期:2003-06-01 00:00:00
abstract::Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosom...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng813
更新日期:2002-02-01 00:00:00
abstract::Genome-wide association studies have previously identified variants in SLC30A8, encoding the zinc transporter ZnT8, associated with diabetes risk. A rare variant association study has now established the direction of effect, surprisingly showing that loss-of-function mutations in SLC30A8 are protective against diabete...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.2934
更新日期:2014-04-01 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::Long noncoding RNAs (lncRNAs) are prevalent genes with frequently precise regulation but mostly unknown functions. Here we demonstrate that lncRNAs guide the organismal DNA damage response. DNA damage activated transcription of the DINO (Damage Induced Noncoding) lncRNA via p53. DINO was required for p53-dependent gen...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3673
更新日期:2016-11-01 00:00:00