Linkage disequilibrium between microsatellite markers extends beyond 1 cM on chromosome 20 in Finns.
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.
Mohlke
K L
KL
Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Lange
E M
EM
Valle
T T
TT
Ghosh
S
S
Magnuson
V L
VL
Silander
K
K
Watanabe
R M
RM
Chines
P S
PS
Bergman
R N
RN
Tuomilehto
J
J
Collins
F S
FS
Boehnke
M
M
D000483:Alleles; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*