Abstract:
:The electrocardiogram has several advantages in detecting cardiac arrhythmia-it is readily available, noninvasive and cost-efficient. Recent genome-wide association studies have identified single-nucleotide polymorphisms that are associated with electrocardiogram measures. We performed a genome-wide association study using Korea Association Resource data for the discovery phase (Phase 1, n = 6805) and two consecutive replication studies in Japanese populations (Phase 2, n = 2285; Phase 3, n = 5010) for QRS duration and PR interval. Three novel loci were identified: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration, and rs17026156 (SLC8A1 locus) correlated with PR interval. PRDM16 was recently identified as a causative gene of left ventricular non-compaction and dilated cardiomyopathy in 1p36 deletion syndrome, which is characterized by heart failure, arrhythmia and sudden cardiac death. Thus, our finding that a PRDM16 SNP is linked to QRS duration strongly implicates PRDM16 in cardiac function. In addition, C allele of rs17026156 increases PR interval (beta ± SE, 2.39 ± 0.40 ms) and exists far more frequently in East Asians (0.46) than in Europeans and Africans (0.05 and 0.08, respectively).
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Hong KW,Lim JE,Kim JW,Tabara Y,Ueshima H,Miki T,Matsuda F,Cho YS,Kim Y,Oh Bdoi
10.1093/hmg/ddu374subject
Has Abstractpub_date
2014-12-15 00:00:00pages
6659-67issue
24eissn
0964-6906issn
1460-2083pii
ddu374journal_volume
23pub_type
杂志文章abstract::Huntington's disease (HD) is one of a class of inherited progressive neurodegenerative disorders that are caused by a CAG/polyglutamine repeat expansion. We have previously generated mice that are transgenic for exon 1 of the HD gene carrying highly expanded CAG repeats which develop a progressive movement disorder an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.5.813
更新日期:1999-05-01 00:00:00
abstract::Dysfunction of mitochondrial translation is an increasingly important molecular cause of human disease, but structural defects of mitochondrial ribosomal subunits are rare. We used next-generation sequencing to identify a homozygous variant in the mitochondrial small ribosomal protein 14 (MRPS14, uS14m) in a patient m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy374
更新日期:2019-02-15 00:00:00
abstract::Myotonic dystrophy (DM) is the most common form of inherited neuromuscular disease in adults and is characterized by progressive muscle wasting and myotonia. The mutation responsible for DM has been identified as the amplification of a polymorphic (CTG)n repeat in the 3' untranslated region of a gene encoding a serine...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.6.1063
更新日期:1995-06-01 00:00:00
abstract::We studied the association between common haplotypes in six relevant lipid metabolism genes with plasma lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic triglyceride lipase (HL), low-density lipoprotein cholesterol rece...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.12.1477
更新日期:2002-06-01 00:00:00
abstract::The defective gene responsible for the recessively inherited immunodeficiency X-linked agammaglobulinemia (XLA) has been shown to encode a cytoplasmic protein tyrosine kinase of the Src family designated Btk (Bruton's tyrosine kinase). To facilitate the search for germline mutations of the Btk gene, we have characteri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1743
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abstract::A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw094
更新日期:2016-06-01 00:00:00
abstract::Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis o...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddu546
更新日期:2015-03-01 00:00:00
abstract::Blepharophimosis syndrome (BPES, blepharophimosis eyelid syndrome) is a distinctive congenital eyelid malformation which can occur sporadically or be inherited in an autosomal dominant fashion. Previous reports have described associated cytogenetic abnormalities on chromosome 3q. We have ascertained and sampled two BP...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.3.443
更新日期:1995-03-01 00:00:00
abstract::Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi482
更新日期:2006-03-01 00:00:00
abstract::Genome-wide association studies and, more recently, next-generation sequencing studies have accelerated the investigation of complex human traits by providing a wealth of association data linking genetic variants to diseases and other phenotypic traits. These data promise to transform our understanding of the molecula...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:2012-10-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.13.1379
更新日期:2001-06-15 00:00:00
abstract::Spinocerebellar ataxia type 2 is an inherited neurodegenerative disorder that is caused by an expanded trinucleotide repeat in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2. Although evidence has been provided that ataxin-2 is involved in RNA metabolism, the physiological function of ata...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi321
更新日期:2005-10-01 00:00:00
abstract::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt364
更新日期:2013-10-15 00:00:00
abstract::The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx155
更新日期:2017-07-15 00:00:00
abstract::Mutations of mitochondrial DNA are linked to many human diseases. Despite the identification of a large number of variants in the mitochondrially encoded rRNA (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best, circumstantial. Establishing the pathogenicity of these variations is of major diagnos...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt490
更新日期:2014-02-15 00:00:00
abstract::Huntington's disease shares a common molecular basis with eight other neurodegenerative diseases, expansion of an existing polyglutamine tract. In each case, this repeat tract occurs within otherwise unrelated proteins. These proteins show widespread and overlapping patterns of expression in the brain and yet the dise...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp455
更新日期:2009-12-15 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disorder caused by mutations in the DMD gene that leads to the absence or severe reduction of dystrophin protein in muscle. The mdx mouse, also dystrophin deficient, is the model most widely used to study the pathology and test potential therapies, but the p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz266
更新日期:2020-02-01 00:00:00
abstract::Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks of amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form of ALS and frontotemporal lobar degeneration (FTLD). Our goal was to pinpoint alterati...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt008
更新日期:2013-04-15 00:00:00
abstract::Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl222
更新日期:2006-09-15 00:00:00
abstract::The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds233
更新日期:2012-09-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2015-12-15 00:00:00
abstract::Four naturally occurring sequence variations have been found in the coding region of the DYT1 gene encoding torsinA. One of these, a 3 bp (DeltaGAG) deletion, underlies dominantly inherited cases of early-onset torsion dystonia. Others, including a single nucleotide polymorphism that replaces aspartic acid (D) at resi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl055
更新日期:2006-04-15 00:00:00
abstract::Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl451
更新日期:2007-01-15 00:00:00
abstract::Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddr270
更新日期:2011-09-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.12.1813
更新日期:2000-07-22 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx375
更新日期:2018-01-01 00:00:00
abstract::Cytoglobin (CYGB) is frequently downregulated in many types of human malignancies, and its exogenous overexpression reduces proliferation of cancer cells. Despite its implied tumour suppressor (TSG) functions, its exact role in carcinogenesis remains unclear as CYGB upregulation is also associated with tumour hypoxia ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt174
更新日期:2013-08-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq506
更新日期:2011-02-01 00:00:00
abstract::Glycogen storage disease type II (GSDII) or Pompe disease is an autosomal recessive disorder caused by defects in the acid alpha-glucosidase gene, which leads to lysosomal glycogen accumulation and enlargement of the lysosomes mainly in cardiac and muscle tissues, resulting in fatal hypertrophic cardiomyopathy and res...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2008-12-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.529
更新日期:1995-04-01 00:00:00