Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family

被引:52
作者
Verge, CF
Vardi, P
Babu, S
Bao, F
Erlich, HA
Bugawan, T
Tiosano, D
Yu, LP
Eisenbarth, GS
Fain, PR
机构
[1] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA
[2] Natl Ctr Childhood Diabet, Petah Tikvah, Israel
[3] Roche Mol Syst, Alameda, CA 94501 USA
关键词
genetics; autoimmunity; chromosome; 10; HLA; genetic linkage;
D O I
10.1172/JCI3379
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Based on a genomic search for linkage, a locus contributing to type I diabetes in a large Bedouin Arab family (19 affected relatives) maps to the long arm of chromosome 10 (10q25; nonparametric linkage = 4.99; P = 0.00004). All affected relatives carry one or two high-risk HLA-DR3 haplotypes that are rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 affected offspring compared to 10 of 23 unaffected siblings. Recombination events occurring on this haplotype place the susceptibility locus in an 8-cM interval between markers D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. A 273-bp allele at D10S592 was transmitted to 8 of 10 affected offspring compared to 3 of 14 unaffected siblings, and a 151-bp allele at D10S554 was transmitted to 15 of 15 affected offspring compared with 10 of 24 unaffected siblings. D10S554 and D10S592 and the closest flanking markers are contained in a 1,240-kb yeast artificial chromosome, a region small enough to proceed with positional cloning.
引用
收藏
页码:1569 / 1575
页数:7
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