Implications of inter-population linkage disequilibrium patterns on the approach to a disease association study in the human MHC class III.
There is presently much interest in utilizing patterns of linkage disequilibrium (LD) to further genetic association studies. This is particularly pertinent in the class III region of the human major histocompatibility complex (MHC), which has been extensively studied as a disease susceptibility locus in a number of ethnic groups. To date, however, few studies of LD in the MHC have considered non-Caucasian populations. With the advent of large-scale haplotyping of the human genome, the question of utilizing LD patterns across populations has come to the fore. We have previously used LD mapping to direct an MHC class III association study in a UK Caucasian population. As an extension of this, we sought to determine to what extent the pattern of LD observed in that study could be used to conduct a similar study in a West African Gambian population. We found that broad patterns of LD were similar in the two populations, resulting in similar candidate region delineations, but at a higher resolution, marker-specific patterns of LD and population-dependent allele frequencies confounded the choice of regional tagging SNPs. Our results have implications for the applicability of large-scale haplotype maps such as the HapMap to complex regions like the MHC.
Hanchard
Neil
N
Wellcome Trust Centre for Human Genetics, Oxford, UK. neil.hanchard@green-oxford.com
Diakite
Mahamadou
M
Koch
Oliver
O
Keating
Brendan
B
Pinder
Margaret
M
Jallow
Muminatou
M
Sisay-Joof
Fatou
F
Nijnik
Anastasia
A
Wilson
Jonathan
J
Udalova
Irina
I
Kwiatkowski
Dominic
D
Rockett
Kirk
K
D002874:Chromosome Mapping; D005006:Ethnicity / Q000235:genetics*; D005714:Gambia / Q000208:ethnology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011153:Population / Q000235:genetics