Linkage disequilibrium between microsatellite markers extends beyond 1 cM on chromosome 20 in Finns

被引:55
作者
Mohlke, KL
Lange, EM
Valle, TT
Ghosh, S
Magnuson, VL
Silander, K
Watanabe, RM
Chines, PS
Bergman, RN
Tuomilehto, A
Collins, FS
Boehnke, M [1 ]
机构
[1] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA
[2] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA
[3] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland
[4] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA
[5] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland
关键词
D O I
10.1101/gr.173201
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, acid 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.
引用
收藏
页码:1221 / 1226
页数:6
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