Genomewide search for type 2 diabetes-susceptibility genes in French whites:: Evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24

被引：569

作者：

Vionnet, N ^{[1
]}

Hani, E ^{[1
]}

Dupont, S ^{[1
]}

Gallina, S ^{[1
]}

Francke, S ^{[1
]}

Dotte, S ^{[1
]}

De Matos, F ^{[1
]}

Durand, E ^{[1
]}

Leprêtre, F ^{[1
]}

Lecoeur, C ^{[1
]}

Gallina, P ^{[1
]}

Zekiri, L ^{[1
]}

Dina, C ^{[1
]}

Froguel, P ^{[1
]}

机构：

[1] CNRS, Inst Biol, Inst Pasteur, F-59000 Lille, France

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2000年 / 67卷 / 06期

关键词：

D O I：

10.1086/316887

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Despite recent advances in the molecular genetics of type 2 diabetes, the majority of susceptibility genes in humans remain to be identified. We therefore conducted a 10-cM genomewide search (401 microsatellite markers) for type 2 diabetes-related traits in 637 members of 143 French pedigrees ascertained through multiple diabetic siblings, to map such genes in the white population. Nonparametric two-point and multipoint linkage analyzes-using the MAPMAXER-SIBS (MLS) and MAXIMUM-BINOMIAL-LIKELIHOOD (MLB) programs for autosomal markers and the ASPEX program for chromosome X markers-were performed with six diabetic phenotypes: diabetes and diabetes or glucose intolerance (GI), as well as with each of the two phenotypes associated with normal body weight (body-mass index<27 kg/m(2)) or early age at diagnosis (<45 years). In a second step, high-resolution genetic mapping (similar to2 cM) was performed in regions on chromosomes 1 and 3 loci showing the strongest linkage to diabetic traits. We found evidence for linkage with diabetes or GI diagnosed at age <45 years in 92 affected sib pairs from 55 families at the D3S1580 locus on chromosome 3q27-qter using MAPMAKER-SIBS (MLS = 4.67, P = .000004), supported by the MLB statistic (MLB-LOD = 3.43, P = .00003). We also found suggestive linkage between the lean diabetic status and markers APOA2-D1S484 (MLS = 3.04, P = .00018; MLB-LOD = 2.99, P = .00010) on chromosome 1q21-q24. Several other chromosomal regions showed indication of linkage with diabetic traits, including markers on chromosome 2p21-p16, 10q26, 20p, and 20q. These results (a) showed evidence for a novel susceptibility locus for type 2 diabetes in French whites on chromosome 3q27-qter and (b) confirmed the previously reported diabetes-susceptibility locus on chromosome 1q21-q24. Saturation on both chromosomes narrowed the regions of interest down to an interval of <7 cM.

引用

页码：1470 / 1480

页数：11

共 55 条

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