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 searching for chromosome segments shared by only three distantly related patients. The screening results were confirmed by identifying an extended haplotype conserved between the patients. Probability calculations indicate that such segment sharing is unlikely to arise by chance. Searching the genome for segments shared by patients is a powerful empirical method for mapping disease genes. Computer simulations suggest that, in appropriate populations, the approach may be used to localize genes for common diseases.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Houwen RH,Baharloo S,Blankenship K,Raeymaekers P,Juyn J,Sandkuijl LA,Freimer NBdoi
10.1038/ng1294-380subject
Has Abstractpub_date
1994-12-01 00:00:00pages
380-6issue
4eissn
1061-4036issn
1546-1718journal_volume
8pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Targeting of cancer stem cells is believed to be essential for curative therapy of cancers, but supporting evidence is limited. Few selective target genes in cancer stem cells have been identified. Here we identify the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSC...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.389
更新日期:2009-07-01 00:00:00
abstract::Pituitary adenoma is one of the most common intracranial neoplasms, and its genetic basis remains largely unknown. To identify genetic susceptibility loci for sporadic pituitary adenoma, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. We first analyzed genome-wide SNP dat...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3322
更新日期:2015-07-01 00:00:00
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::The ratio of X-linked to autosomal diversity was estimated from an analysis of six human genome sequences and found to deviate from the expected value of 0.75. However, the direction of this deviation depends on whether a particular sequence is close to or far from the nearest gene. This pattern may be explained by st...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.651
更新日期:2010-10-01 00:00:00
abstract::Epilepsy affects at least 2% of the population at some time in their lives. The epilepsies are a heterogeneous group of disorders, many with an inherited component. Although specific genes have been identified in a few rare diseases causing seizures as part of a more diffuse brain disorder, the molecular pathology of ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1095-201
更新日期:1995-10-01 00:00:00
abstract::Polymicrogyria is a relatively common but poorly understood defect of cortical development characterized by numerous small gyri and a thick disorganized cortical plate lacking normal lamination. Here we report de novo mutations in a beta-tubulin gene, TUBB2B, in four individuals and a 27-gestational-week fetus with bi...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.380
更新日期:2009-06-01 00:00:00
abstract::A study of genetic variation in yeast has identified key quantitative trait loci (QTLs) that suppress the effects of variation at multiple other loci. These loci prove essential to accurately modeling yeast growth in response to different environments. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3829
更新日期:2017-03-30 00:00:00
abstract::To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = ...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.567
更新日期:2010-05-01 00:00:00
abstract::Mutation of the gene PARK2, which encodes an E3 ubiquitin ligase, is the most common cause of early-onset Parkinson's disease. In a search for multisite tumor suppressors, we identified PARK2 as a frequently targeted gene on chromosome 6q25.2-q27 in cancer. Here we describe inactivating somatic mutations and frequent ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.491
更新日期:2010-01-01 00:00:00
abstract::We conducted a meta-analysis of genome-wide association data to detect genes influencing age at menarche in 17,510 women. The strongest signal was at 9q31.2 (P = 1.7 × 10(-9)), where the nearest genes include TMEM38B, FKTN, FSD1L, TAL2 and ZNF462. The next best signal was near the LIN28B gene (rs7759938; P = 7.0 × 10(...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.386
更新日期:2009-06-01 00:00:00
abstract::The pathogenesis of Bacillus anthracis, the bacterium that causes anthrax, depends on secretion of three factors that combine to form two bipartite toxins. Edema toxin, consisting of protective antigen (PA) and edema factor (EF), causes the edema associated with cutaneous anthrax infections, whereas lethal toxin (LeTx...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1724
更新日期:2006-02-01 00:00:00
abstract::Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for repli...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.2249
更新日期:2012-04-15 00:00:00
abstract::Polycomb Group (PcG) proteins silence critical developmental genes and modulate cell proliferation. Using the Drosophila melanogaster eye as a model system, we show that cells with mutations in the gene locus (ph) that encodes the PcG protein Polyhomeotic (PH) overproliferate and lose both the ability to differentiate...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.414
更新日期:2009-10-01 00:00:00
abstract::Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expre...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng731
更新日期:2001-10-01 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::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::Upon detection of pathogen-associated molecular patterns, innate immune receptors initiate inflammatory responses. These receptors include cytoplasmic NOD-like receptors (NLRs) whose stimulation recruits and proteolytically activates caspase-1 within the inflammasome, a multiprotein complex. Caspase-1 mediates the pro...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3066
更新日期:2014-10-01 00:00:00
abstract::Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70-80% of kidney stones, and small changes in urinary oxalate concentration affect the risk of stone formation. SLC26A6 is an anion exchanger expressed on the apical membrane in many ep...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1762
更新日期:2006-04-01 00:00:00
abstract::The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1943
更新日期:2007-02-01 00:00:00
abstract::Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precanc...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2796
更新日期:2013-12-01 00:00:00
abstract::The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitina...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2323
更新日期:2012-06-10 00:00:00
abstract::Errors in meiotic chromosome segregation are the leading cause of spontaneous abortions and birth defects. In humans, chromosomes that fail to experience crossovers (or exchanges) are error-prone, more likely than exchange chromosomes to mis-segregate in meiosis. We used a yeast model to investigate the mechanisms tha...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1588
更新日期:2005-07-01 00:00:00
abstract::Genetic recombination is a major force driving the evolution of many viruses. Recombination between two copackaged retroviral genomes may occur at rates as high as 40% per replication cycle. This enables genetic information to be shuffled rapidly, leading to recombinants with new patterns of mutations and phenotypes. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/78132
更新日期:2000-08-01 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::The Drosophila melanogaster gene Dscam is essential for axon guidance and has 38,016 possible alternative splice forms. This diversity can potentially be used to distinguish cells. We analyzed the Dscam mRNA isoforms expressed by different cell types and individual cells. The choice of splice variants expressed is reg...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1299
更新日期:2004-03-01 00:00:00
abstract::Wilson disease (WD) is an autosomal recessive disorder of copper transport which map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1293-338
更新日期:1993-12-01 00:00:00
abstract::The Ras signal transduction pathway is often deregulated in human myeloid leukaemia. For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase acti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0296-137
更新日期:1996-02-01 00:00:00
abstract::Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular path...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.892
更新日期:2011-07-31 00:00:00
abstract::Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment and therefore represent a classic example of convergent evolution. To investigate convergent evolution at the genomic level, we sequenced and performed de novo assembly of the genomes of three species of m...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3198
更新日期:2015-03-01 00:00:00
abstract::We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associate...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.784
更新日期:2011-03-06 00:00:00