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 demanding task, despite many recent advances in technology for the production of high-density microarrays. A key technical obstacle is the PCR amplification step, which is required to reduce the complexity of and gain sufficient sensitivity for genotyping SNPs in large, diploid genomes. The multiplexing level that can be achieved in PCR does not match that of current microarray-based methods, making PCR the limiting step in the assays. Highly multiplexed microarray systems for SNP genotyping have recently been developed by combining well-known reaction principles for DNA amplification and SNP genotyping in clever ways. These new methods offer the potential of genome-wide SNP mapping of genes involved in complex diseases in the foreseeable future, provided that issues related to selection of the optimal SNP markers, sample throughput and the cost of the assays can be addressed.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Syvänen ACdoi
10.1038/ng1558keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
S5-10eissn
1061-4036issn
1546-1718pii
ng1558journal_volume
37 Supplpub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::The three-dimensional organization of the genome has an important role in orchestrating gene expression, but its regulation is poorly understood. Now, a new study uncovers a major role for Polycomb components of the PRC1 complex in organizing physical networks of genes that are co-repressed to maintain pluripotency. ...
journal_title:Nature genetics
pub_type: 评论,新闻
doi:10.1038/ng.3411
更新日期:2015-10-01 00:00:00
abstract::Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppr...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3728
更新日期:2017-01-01 00:00:00
abstract::Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng893
更新日期:2002-08-01 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::To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CH...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3943
更新日期:2017-10-01 00:00:00
abstract::Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two-step cycling process that ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0693-135
更新日期:1993-06-01 00:00:00
abstract::Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have ge...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng914
更新日期:2002-08-01 00:00:00
abstract::We developed a likelihood-based approach for analyzing summary-level statistics and external linkage disequilibrium information to estimate effect-size distributions of common variants, characterized by the proportion of underlying susceptibility SNPs and a flexible normal-mixture model for their effects. Analysis of ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0193-x
更新日期:2018-09-01 00:00:00
abstract::We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1122
更新日期:2003-04-01 00:00:00
abstract::Interindividual variability in drug response, ranging from no therapeutic benefit to life-threatening adverse reactions, is influenced by variation in genes that control the absorption, distribution, metabolism and excretion of drugs. We genotyped 904 single-nucleotide polymorphisms (SNPs) from 55 such genes in two po...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1488
更新日期:2005-01-01 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::Atopic or immunoglobulin E (IgE)-mediated diseases include the common disorders of asthma, atopic dermatitis and allergic rhinitis. Chromosome 13q14 shows consistent linkage to atopy and the total serum IgE concentration. We previously identified association between total serum IgE levels and a novel 13q14 microsatell...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1166
更新日期:2003-06-01 00:00:00
abstract::After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10(-9))....
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.1080
更新日期:2012-02-05 00:00:00
abstract::Three new studies have identified new genes and sequence variants implicated in blood lipids, inflammatory markers, hemoglobin levels and adult height variation in Sardinia. These reports highlight the usefulness of large-scale genotype imputation based on whole-genome sequencing, particularly in isolated populations,...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3426
更新日期:2015-11-01 00:00:00
abstract::Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associat...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3268
更新日期:2015-06-01 00:00:00
abstract::Kallmann syndrome is a genetic disorder characterized by a defect in olfactory system development, which appears to be due to an abnormality in the migration of olfactory axons and gonadotropin releasing hormone (Gn-RH) producing neurons. The X-linked Kallmann syndrome gene shares significant similarities with molecul...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0593-19
更新日期:1993-05-01 00:00:00
abstract::The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the hu...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2007.34
更新日期:2008-01-01 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::Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. Electromyographic investigations reveal repetitive m...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/82638
更新日期:2000-12-01 00:00:00
abstract::Aggregate results from genome-wide association studies (GWAS), such as genotype frequencies for cases and controls, were until recently often made available on public websites because they were thought to disclose negligible information concerning an individual's participation in a study. Homer et al. recently suggest...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.455
更新日期:2009-11-01 00:00:00
abstract::We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions sur...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0081-4
更新日期:2018-04-01 00:00:00
abstract::We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis s...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2213
更新日期:2012-03-18 00:00:00
abstract::Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These find...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3040
更新日期:2014-08-01 00:00:00
abstract::The degree to which genetic factors influence human intelligence remains a matter of some controversy. However, there is little doubt that single gene mutations can significantly alter brain development and function. For example, mutations affecting the FMR1 gene cause the fragile X syndrome, the most prevalent known ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1195-331
更新日期:1995-11-01 00:00:00
abstract::Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in severa...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng994
更新日期:2002-10-01 00:00:00
abstract::The combination of inhibition of RNA degradation and comparative genomic scanning is a powerful new method for detecting gene disruptions. The utility of the method is well-illustrated by a series of observations linking the ephrin receptor EPHB2 to prostate cancer. ...
journal_title:Nature genetics
pub_type: 评论,新闻
doi:10.1038/ng0904-937
更新日期:2004-09-01 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::Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in riboso...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3661
更新日期:2016-10-01 00:00:00
abstract::Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The pla...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2604
更新日期:2013-05-01 00:00:00
abstract::The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attem...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng2068
更新日期:2007-07-01 00:00:00