Ghosh S, Watanabe R M, Valle T T, Hauser E R, Magnuson V L, Langefeld C D, Ally D S, Mohlke K L, Silander K, Kohtamäki K, Chines P, Balow J, Birznieks G, Chang J, Eldridge W, Erdos M R, Karanjawala Z E, Knapp J I, Kudelko K, Martin C, Morales-Mena A, Musick A, Musick T, Pfahl C, Porter R, Rayman J B
Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Am J Hum Genet. 2000 Nov;67(5):1174-85. Epub 2000 Oct 13.
We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.
我们对719对患有2型糖尿病的芬兰同胞对进行了平均分辨率为8厘摩（cM）的全基因组扫描。我们最显著的结果出现在20号染色体上，在距短臂末端（pter）69.5厘摩的图谱位置观察到加权最大对数优势分数（MLS）为2.15，在56.5厘摩处有次强加权LOD分数峰值2.04，在17.5厘摩处为1.99。我们第二大的MLS出现在11号染色体上（在84.0厘摩处MLS = 1.75），其次是2号染色体（在5.5厘摩处MLS = 0.87）、10号染色体（在75.0厘摩处MLS = 0.77）和6号染色体（在112.5厘摩处MLS = 0.61），所有这些均基于加性模型。当我们以8.5厘摩处的2号染色体为条件时，20号染色体在69.0厘摩处的MLS增加到5.50（P = 0.0014）。基于糖尿病相关数量性状高或低的家庭进行的有序子集分析产生的结果支持6号和10号染色体上可能存在疾病易感基因。使用微卫星标记数据进行的全基因组连锁不平衡分析揭示了D22S423存在强关联证据（P = 0.00007）。正在进行进一步分析以确认并细化这些推定的糖尿病易感基因的位置。
