J Korean Med Sci.  2007 Jun;22(3):425-430. 10.3346/jkms.2007.22.3.425.

Distinct Linkage Disequilibrium (LD) Runs of Single Nucleotide Polymorphisms and Microsatellite Markers; Implications for Use of Mixed Marker Haplotypes in LD-based Mapping

• Lee KA
• Sohn KM
• Cho SH
• Hwang H
• Kim SW
• Won HH
• Kim HJ
• Kim MJ
• Cho SS
• Park JH
• Kim JW

• KMID: 1778348
• DOI: http://doi.org/10.3346/jkms.2007.22.3.425

Abstract

It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers.

Keyword

Single Nucleotide Polymorphisms; Microsatellite Markers; Linkage Disequilibrium

MeSH Terms

Algorithms
Chromosome Mapping
Chromosomes, Human, Pair 22
Genetics, Population
Genotype
Great Britain
*Haplotypes
Heterozygote
Humans
Iceland
Korea
*Linkage Disequilibrium
Microsatellite Repeats/*genetics
Mutation
*Polymorphism, Single Nucleotide

Figure

• 

  Fig. 1 Comparison of the linkage disequilibrium (LD) patterns among single nucleotide polymorphisms (SNPs) in the Korean and UK populations. (A) Average D' and γ2 coefficients (top and bottom groups, respectively) plotted in sliding windows containing all common polymorphisms separated by 50 and 500 kb in successive 1.7-Mb segments. (B) D' confidence limits calculated by the bootstrap method. The upper (U) and lower (L) bounds represents the 5% tails of the overall probability distribution. Two enhanced views provide the D' confidence limits from 24-32 Mb and 33-41 Mb, respectively. Korean, green; U.K., red.

• 

  Fig. 2 Comparison of the linkage disequilibrium (LD) patterns among microsatellite markers in the Korean and Icelandic populations. (A) D' coefficients estimated by the EM algorithm in the Icelandic founders and calculated by bootstrap and permutation with haplotype data constructed from the Icelandic family genotype data. (B) D' coefficients (heterozygosity 0.657 and 0.668 in the Korean and Icelandic populations, respectively). (C) D' confidence limits calculated by bootstrap method. The upper (U) and lower (L) bounds represent the 5% tails of the overall probability distribution. Korean, green; Icelander, red.

• 

  Fig. 3 Comparison of the LD patterns detected using SNP and microsatellite markers in the Korean population. (A) Average D' plotted in sliding window containing all common SNPs and D' coefficients of microsatellite markers. (B) D' confidence limits. Microsatellite markers, green; SNPs, red.

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