Mohlke K L, Lange E M, Valle T T, Ghosh S, Magnuson V L, Silander K, Watanabe R M, Chines P S, Bergman R N, Tuomilehto J, Collins F S, Boehnke M
Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Genome Res. 2001 Jul;11(7):1221-6. doi: 10.1101/gr.173201.
Linkage disequilibrium (LD) is a proven tool for evaluating population structure and localizing genes for monogenic disorders. LD-based methods may also help localize genes for complex traits. We evaluated marker-marker LD using 43 microsatellite markers spanning chromosome 20 with an average density of 2.3 cM. We studied 837 individuals affected with type 2 diabetes and 386 mostly unaffected spouse controls. A test of homogeneity between the affected individuals and their spouses showed no difference, allowing the 1223 individuals to be analyzed together. Significant (P < 0.01) LD was observed using a likelihood ratio test in all (11/11) marker pairs within 1 cM, 78% (25/32) of pairs 1-3 cM apart, and 39% (7/18) of pairs 3-4 cM apart, but for only 12 of 842 pairs more than 4 cM apart. We used the human genome project working draft sequence to estimate kilobase (kb) intermarker distances, and observed highly significant LD (P < 10(-10)) for all six marker pairs up to 350 kb apart, although the correlation of LD with cM is slightly better than the correlation with megabases. These data suggest that microsatellites present at 1-cM density are sufficient to observe marker-marker LD in the Finnish population.
连锁不平衡（LD）是评估群体结构和定位单基因疾病基因的一种成熟工具。基于LD的方法也可能有助于定位复杂性状的基因。我们使用跨越20号染色体的43个微卫星标记评估标记-标记LD，平均密度为2.3厘摩（cM）。我们研究了837名2型糖尿病患者和386名大多未患病的配偶对照。对患病个体及其配偶之间的同质性检验显示无差异，从而可以将这1223名个体一起进行分析。使用似然比检验观察到，在距离1厘摩以内的所有（11/11）标记对中、距离1 - 3厘摩的标记对中有78%（25/32）以及距离3 - 4厘摩的标记对中有39%（7/18）存在显著（P < 0.01）的LD，但在距离超过4厘摩的842个标记对中只有12个存在显著LD。我们使用人类基因组计划工作草图序列来估计标记间的千碱基（kb）距离，并观察到距离达350 kb的所有六对标记均存在高度显著的LD（P < 10⁻¹⁰），尽管LD与厘摩的相关性略优于与兆碱基（Mb）的相关性。这些数据表明，以1厘摩密度存在的微卫星足以在芬兰人群中观察到标记-标记LD。
