Abstract:
:Lower plasma levels of high-density lipoprotein cholesterol (HDL-C) are associated with the metabolic syndrome (insulin resistance, obesity, hypertension) and higher cardiovascular risk. Recent association studies have suggested rare alleles responsible for very low HDL-C levels. However, for individual cardiovascular risk factors, the majority of population-attributable deaths are associated with average rather than extreme levels. Therefore, genetic factors that determine the population variation of HDL-C are particularly relevant. We undertook genome-wide and fine mapping to identify linkage to HDL-C in healthy adult nuclear families from the Victorian Family Heart Study. In 274 adult sibling pairs (average age 24 years, average plasma HDL-C 1.4 mmol/l), genome-wide mapping revealed suggestive evidence for linkage on chromosome 4 (Z score = 3.5, 170 cM) and nominal evidence for linkage on chromosomes 1 (Z = 2.1, 176 cM) and 6 (Z = 2.6, 29 cM). Using genotypes and phenotypes from 932 subjects (233 of the sibling pairs and their parents), finer mapping of the locus on chromosome 4 strengthened our findings with a peak probability (Z score = 3.9) at 169 cM. Our linkage data suggest that chromosome 4q32.3 is linked with normal population variation in HDL-C. This region coincides with previous reports of linkage to apolipoprotein AII (a major component of HDL) and encompasses the gene encoding the carboxypeptidase E, relevant to the metabolic syndrome and HDL-C. These findings are relevant for further understanding of the genetic determinants of cardiovascular risk at a population level.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Harrap SB,Wong ZY,Scurrah KJ,Lamantia Adoi
10.1007/s00439-006-0167-4keywords:
subject
Has Abstractpub_date
2006-06-01 00:00:00pages
541-6issue
5eissn
0340-6717issn
1432-1203journal_volume
119pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::A cystinuria disease gene (rBAT) has recently been identified, but evidence strongly suggests that only Type-I cystinuria is due to mutations in this gene. Sixteen point mutations and a large deletion causing the disease have so far been described in the rBAT gene sequence. To identify new mutated alleles, genomic DNA...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050237
更新日期:1996-10-01 00:00:00
abstract::The gene frequency of beta-thalassemia among Filipinos is estimated to be 0.02, although little is known about the mutations involved. Recently, an extensive beta-thalassemia deletion was reported in several unrelated individuals of Filipino descent. The deletion begins approximately 4 kb upstream of the beta-globin g...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00211021
更新日期:1994-11-01 00:00:00
abstract::Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However, the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify additional novel breast cancer susceptibility variants and to rep...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-0973-1
更新日期:2011-10-01 00:00:00
abstract::A case of partial trisomy 9 is described in a mentally retarded and dysmorphic child, confirming that this chromosome unbalance results in a characteristic clinical entity. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in the patient's mother, who is a balanced heterozygote...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00447289
更新日期:1976-07-07 00:00:00
abstract::A new G6PD variant has been detected in a Cuban male and there is no evidence of associated hematological abnormalities. The main characteristics of this variant, moderate deficiency, slow electrophoretic mobility, increased utilization of the substrate analogues, and a different chromatographic behavior, indicate tha...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00329141
更新日期:1980-01-01 00:00:00
abstract::A girl with 46, XX, del (11) (q23), inv (9) (p13, q13) is described. The patient shows many dysplastic signs mainly of the face and skull. The pericentric inversion of chromosome 9 has been inherited from the mother (46, XX, inv (9) (p13, q13)). ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00390443
更新日期:1977-04-07 00:00:00
abstract::A polymorphism was identified in 3' untranslated region of the phenylalanine hydroxylase gene using the newly described mutation detection method, enzyme mismatch cleavage. This polymorphism, 1546 G-->A, was linked to three mutations on several haplotype backgrounds. A group of haplotypes was identified as evolving fr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00210312
更新日期:1995-12-01 00:00:00
abstract::Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease characterized by fibro-fatty replacement of right ventricular free wall myocardium and life-threatening ventricular arrhythmias. A missense mutation, c.1073C>T (p.S358L) in the transmembrane protein 43 (TMEM43) gene, has been genetically id...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-013-1323-2
更新日期:2013-11-01 00:00:00
abstract::Development of protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG to Fc gamma (γ) receptors. Variations in human FcγRIIA-H/R-131 and FcγRIIIB-NA1/NA2 affect differential binding of IgG sub-classes. Since variability in FcγR may play an important role in seve...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-1076-8
更新日期:2012-02-01 00:00:00
abstract::We have described a novel human globin gene mutation that produced in a Japanese family the beta-thalassemia phenotype through a post-translational mechanism. Substitution of proline for leucine at position 110 in the G-helix of the beta-globin chain greatly reduced the molecular stability of the beta-globin subunit, ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00451448
更新日期:1988-09-01 00:00:00
abstract::The human gene locus c-MEL was identified following transfection of genomic DNA from the human melanoma cell line NK14; it has previously been assigned to chromosome 19 (p13.2-q13.2) by analysis of somatic cell hybrids. We have further refined the position of this gene to the proximal region of 19p (cen-p13.2), using ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00283697
更新日期:1989-03-01 00:00:00
abstract::Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, oppo...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1455-z
更新日期:2014-09-01 00:00:00
abstract::The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS)...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284570
更新日期:1985-01-01 00:00:00
abstract::To help unravel some of the early Eurasian steppe migration movements, we determined the Y-chromosomal and mitochondrial haplotypes and haplogroups of 26 ancient human specimens from the Krasnoyarsk area dated from between the middle of the second millennium BC. to the fourth century AD. In order to go further in the ...
journal_title:Human genetics
pub_type: 历史文章,杂志文章
doi:10.1007/s00439-009-0683-0
更新日期:2009-09-01 00:00:00
abstract::Qualitative and quantitative defects in human germ cell production that result in infertility are common and determined at least in part by genetic factors [Matzuk and Lamb, Nat Cell Biol 4(Suppl):s41-s49, 2002]. Yet, very few genes that are associated with germ cell defects in humans have been identified. In this stu...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-0098-5
更新日期:2006-02-01 00:00:00
abstract::DNA sequence analysis and electrophoresis in denaturing gel revealed that a 60 base pair insertion which had been previously postulated on the basis of native polyacrylamide gel electrophoresis of mitochondrial DNA from Japanese (Horai and Matsunaga 1986) did not exist at all. Unusual behavior of certain restriction f...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00273844
更新日期:1987-01-01 00:00:00
abstract::Amplification of the beta-globin gene by the polymerase chain reaction (PCR) and direct sequencing were used for a fast and reliable identification of the beta-globin variant Hb D Los Angeles and revealed the predicted G----C substitution in codon 121. The same method showed the molecular defect in Hb Presbyterian to ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00196236
更新日期:1990-03-01 00:00:00
abstract::Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormal...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00292373
更新日期:1983-01-01 00:00:00
abstract::Chorionic villi were obtained by an aspiration technique which proved to be the best of four alternative procedures. We report in detail the series of experiments which led to (1) successful, rapidly growing cell cultures practically free of maternal cell contamination (the use of hormone-supplemented Chang medium gre...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00274761
更新日期:1983-01-01 00:00:00
abstract::The hyperinsulinism-hyperammonemia syndrome (HHS) has been shown to result from 'gain-of-function' mutations of the glutamate dehydrogenase (GlDH) gene, GLUD1. In the original report, all mutations were found in a narrow range of 27 base pairs within exons 11 and 12 which predicted an effect on the presumed allosteric...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000432
更新日期:2001-01-01 00:00:00
abstract::While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more e...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0219-9
更新日期:2006-11-01 00:00:00
abstract::Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag SNPs in these genes with insulin sensitivity was examined in a c...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-008-0595-4
更新日期:2009-02-01 00:00:00
abstract::Southern African Bantu-speaking negroid and San populations were examined with regard to the glucose-6-phosphate dehydrogenase (G6PD) PvuII restriction fragment length polymorphism (RFLP) showing alleles of 4 kb and 1.6 kb, called Type 1 and Type 2, respectively. The standardized disequilibrium coefficient for the ele...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00207056
更新日期:1992-04-01 00:00:00
abstract::A new mutant alpha-1-antichymotrypsin (variant ACT) was found by polymerase chain reaction single strand conformation polymorphism and direct sequencing. In this variant ACT, two bases (AA) were deleted from codon 391. This resulted in a different amino acid sequence downstream of the deletion point, elongating the pe...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00220480
更新日期:1992-12-01 00:00:00
abstract::To initiate the complete characterization of mutations in the CFTR gene in Greek cystic fibrosis (CF) patients, we screened 184 patients for six relatively common mutations (delta F 508, G542X, G551D, 621 + 1 G-->T, N1303K, W1282X) using allele-specific hybridization and, in addition, analyzed exons 4, 5, 7, 8, 10, 11...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00210426
更新日期:1995-09-01 00:00:00
abstract::We describe a comparative study of the behavior of nucleolar structures and their relationship with nucleolar chromosomes and synaptonemal complexes at first meiotic prophase of human oocytes in an attempt to elucidate the nature of this cellular organization and to learn more about maternal nondisjunction. The number...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284048
更新日期:1989-05-01 00:00:00
abstract::We tested DNA probes directly labeled by fluorescently labeled nucleotides (Cy3-dCTP, Cy5-dCTP, FluorX-dCTP) for high resolution uni- and multicolor detection of human chromosomes and analysis of centromeric DNA organization by in situ hybridization. Alpha-satellite DNA probes specific to chromosomes 1, 2, 3, 4 + 9, 5...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02185780
更新日期:1996-03-01 00:00:00
abstract::The phenotype AK 3.3 in the isoenzyme system of human adenylate kinase has been found in two members of the Wayampi population of French Guiana. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278843
更新日期:1978-09-19 00:00:00
abstract::Premature ovarian failure (POF) is an unexplained amenorrhoea (>6 months) with raised levels of gonadotropins (FSH>40 U/L) occurring before the age of 40 years. Recent studies have elucidated the role of oocyte derived growth factors (BMP15 and GDF9) in maintenance of folliculogenesis, granulosa cell (GC) proliferatio...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0150-0
更新日期:2006-05-01 00:00:00
abstract::A young female was diagnosed as having X-linked muscular dystrophy of the Duchenne type. Chromosome studies, including trypsin-Giemsa banding, Quinacrine fluorescence, and nucleolus organizer region (NOR) silver staining revealed an X-autosome reciprocal translocation t(X;21) (p21;p12). Utilizing both [3H] thymidine a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00270570
更新日期:1984-01-01 00:00:00