Statistical estimation and pedigree analysis of CCR2-CCR5 haplotypes.

Area of Science:

• Genetics
• Population Genetics
• Bioinformatics

Background:

• Haplotype analysis, using linked markers, is increasingly preferred over individual polymorphisms for association studies.
• Estimating haplotypes without family data or phase-determining lab methods is crucial for population-based case-control studies.

Purpose of the Study:

• To evaluate the accuracy of the Expectation-Maximization (EM) algorithm for estimating haplotype states and frequencies in the CCR2-CCR5 gene region.
• To compare EM algorithm results with those obtained from pedigree analysis.
• To determine CCR2-CCR5 allele and haplotype frequencies in diverse populations for genetic epidemiology.

Main Methods:

• Characterized haplotypes at seven biallelic loci within a 20 kb span of the CCR2-CCR5 gene region.
• Utilized three-generation CEPH families (n=40, 489 individuals) genotyped via 5'nuclease assay (TaqMan).
• Compared EM algorithm estimations with pedigree analysis in 103 randomly mated grandparents.

Main Results:

• Both pedigree analysis and the EM algorithm identified a small number of haplotypes with near-maximal linkage disequilibrium.
• Haplotype frequencies estimated by both methods were nearly identical.
• The EM algorithm proved effective for analyzing haplotype states, frequencies, and linkage disequilibrium in the CCR2-CCR5 region.

Conclusions:

• The EM algorithm is a reliable and effective strategy for haplotype estimation in the CCR2-CCR5 gene region, particularly for genetic epidemiology.
• The study provides essential CCR2-CCR5 allele and haplotype frequency data for African-American, Hispanic, and European-American populations.