Ghosh S, Hauser E R, Magnuson V L, Valle T, Ally D S, Karanjawala Z E, Rayman J B, Knapp J I, Musick A, Tannenbaum J, Te C, Eldridge W, Shapiro S, Musick T, Martin C, So A, Witt A, Harvan J B, Watanabe R M, Hagopian W, Eriksson J, Nylund S J, Kohtamaki K, Tuomilehto-Wolf E, Boehnke M
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1998 Aug 15;102(4):704-9. doi: 10.1172/JCI2512.
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 lambdas (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 </= -2) for lambdas >/= 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.
在首次报道的非胰岛素依赖型糖尿病(NIDDM)基因组扫描阳性结果中,哈尼什等人发现了2号染色体q37区域存在NIDDM连锁的重要证据,并将这个假定的疾病位点命名为NIDDM1(哈尼什等人,1996年。《自然遗传学》13:161 - 166)。他们的总样本包括来自246个同胞对的440个墨西哥裔美国患病同胞对。连锁的最强证据出现在标记D2S125处,使用该标记对λ值(先证者同胞的患病风险/人群患病率)的最佳估计在加性模型下为1.37,在乘性模型下为1.36。我们在一个由来自472个同胞对的709个患病同胞对组成的芬兰样本中,使用连锁分析研究了这个染色体区域。对于λ值≥1.37的情况,我们在样本中排除了这个区域(多点对数优势比分≤ -2)。我们讨论了未发现与2q37连锁的可能原因,并得出结论,在芬兰白种人群中,该区域不太可能在NIDDM易感性中起主要作用。