A large sample of Finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter

被引:19
作者
Ghosh, S
Hauser, ER
Magnuson, VL
Valle, T
Ally, DS
Karanjawala, ZE
Rayman, JB
Knapp, JI
Musick, A
Tannenbaum, J
Te, C
Eldridge, W
Shapiro, S
Musick, T
Martin, C
So, A
Witt, A
Harvan, JB
Watanabe, RW
Hagopian, W
Eriksson, J
Nylund, SJ
Kohtamaki, K
Tuomilehto-Wolf, E
Toivanen, L
Vidgren, G
Ehnholm, C
Bergman, RN
Tuomilehto, J
Collins, FS
Boehnke, M
机构
[1] NIH, Genet & Mol Biol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA
[2] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA
[3] Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, FIN-00300 Helsinki, Finland
[4] Univ Washington, Dept Med, Seattle, WA 98195 USA
[5] Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA
关键词
gene mapping; affected sib-pairs; non-insulin-dependent diabetes mellitus fluorescent genotyping; linkage analysis;
D O I
10.1172/JCI2512
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
In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambda(s) (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score less than or equal to -2) for lambda(s) greater than or equal to 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.
引用
收藏
页码:704 / 709
页数:6
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