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 Caenorhabditis elegans characterized by deletions that start around the 3' end of polyguanine tracts and terminate at variable positions 5' from such tracts. We observed deletions throughout genomic DNA in about half of polyguanine tracts examined, especially those containing 22 or more consecutive guanine nucleotides. The mutator phenotype results from disruption of the predicted gene F33H2.1, which encodes a protein with characteristics of a DEAH helicase and which we have named dog-1 (for deletions of guanine-rich DNA). Nematodes mutated in dog-1 showed germline as well as somatic deletions in genes containing polyguanine tracts, such as vab-1. We propose that DOG-1 is required to resolve the secondary structures of guanine-rich DNA that occasionally form during lagging-strand DNA synthesis.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Cheung I,Schertzer M,Rose A,Lansdorp PMdoi
10.1038/ng928keywords:
subject
Has Abstractpub_date
2002-08-01 00:00:00pages
405-9issue
4eissn
1061-4036issn
1546-1718pii
ng928journal_volume
31pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::The tissue-specific organization of collagen molecules into tridimensional macroaggregates determines the physiomechanical properties of most connective tissues, but the factors and mechanisms controlling this process are unknown. It has been postulated that quantitatively minor types V and XI collagen regulate the gr...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0195-31
更新日期:1995-01-01 00:00:00
abstract::Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0598-98
更新日期:1998-05-01 00:00:00
abstract::We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide cha...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0395-279
更新日期:1995-03-01 00:00:00
abstract::Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes us...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2273
更新日期:2012-05-06 00:00:00
abstract::G-quadruplex (G4) structural motifs have been linked to transcription, replication and genome instability and are implicated in cancer and other diseases. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context. Herein we address this through the developmen...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3662
更新日期:2016-10-01 00:00:00
abstract::The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occu...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.710
更新日期:2010-12-01 00:00:00
abstract::We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and a...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1636
更新日期:2005-10-01 00:00:00
abstract::Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashio...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng942
更新日期:2002-09-01 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::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::Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mut...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2935
更新日期:2014-05-01 00:00:00
abstract::We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng798
更新日期:2002-01-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (ca...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.670
更新日期:2010-11-01 00:00:00
abstract::A new study shows that HOXB13 is preferentially recruited to the risk allele of a prostate cancer-associated SNP, enhancing the expression of RFX6, a driver of prostate cancer cell migration and predictor of disease progression. The work illustrates how a single risk locus contributes both to prostate cancer incidence...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.2881
更新日期:2014-02-01 00:00:00
abstract::Human telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends. One component of human telomeres is the TTAGGG repeat binding factor 1 (TRF1), a ubiquitously expressed protein, related to the protooncogene Myb, that is pres...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1097-231
更新日期:1997-10-01 00:00:00
abstract::Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of spo...
journal_title:Nature genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/ng.2636
更新日期:2013-07-01 00:00:00
abstract::Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2252
更新日期:2012-05-01 00:00:00
abstract::Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.2397
更新日期:2012-10-01 00:00:00
abstract::Acquired mutations in the hematopoietic transcription factor GATA binding protein-1 (GATA1) are found in megakaryoblasts from nearly all individuals with Down syndrome with transient myeloproliferative disorder (TMD, also called transient leukemia) and the related acute megakaryoblastic leukemia (DS-AMKL, also called ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1566
更新日期:2005-06-01 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::Epileptic encephalopathies are severe brain disorders with the epileptic component contributing to the worsening of cognitive and behavioral manifestations. Acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and continuous spike and waves during slow-wave sleep syndrome (CSWSS) represent rare and closely relat...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2726
更新日期:2013-09-01 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::White sponge nevus (WSN) is a benign autosomal dominant disorder which affects non-cornifying stratified squamous epithelia (MIM 193900) (ref. 1). Phenotypically it presents as white 'spongy' plaques (oral leukokeratoses), most commonly in the mouth but also reported in the esophagus and anogenital mucosa. Histologica...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1295-450
更新日期:1995-12-01 00:00:00
abstract::Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/90050
更新日期:2001-07-01 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::We identified the gene carrying the juvenile spermatogonial depletion mutation (jsd), a recessive spermatogenic defect mapped to mouse chromosome 1 (refs. 1,2). We localized jsd to a 272-kb region and resequenced this area to identify the underlying mutation: a frameshift that severely truncates the predicted protein ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1390
更新日期:2004-08-01 00:00:00
abstract::In the version of the article published, the author list is not accurate. Igor Cima and Min-Han Tan should have been authors, appearing after Mark Wong in the author list, while Paul Jongjoon Choi should not have been listed as an author. Igor Cima and Min-Han Tan both have the affiliation Institute of Bioengineering ...
journal_title:Nature genetics
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41588-018-0299-1
更新日期:2018-12-01 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::Stem cell regulation is critical to the development of all multicellular organisms; in plants, stem cell niches reside in meristems. Two newly identified plant genes establish a novel signaling feedback from the incipient leaf primordia back to the meristem that is required to regulate stem cell proliferation. ...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.3601
更新日期:2016-06-28 00:00:00
abstract::Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two d...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2917
更新日期:2014-04-01 00:00:00