Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC.
Detailed knowledge of linkage disequilibrium (LD) is regarded as a prerequisite for population-based disease gene mapping. Variable patterns across the human genome are now recognized, both between regions and populations. Here, we demonstrate that LD may also vary within a genomic region in a haplotype-specific manner. In 864 Caucasian unrelated individuals, we describe haplotype-specific LD patterns across the human MHC by the construction of gene-specific allelic haplotypes at 25 loci between HLA-A and Tapasin. Strong and extensive LD is found across both common and rare haplotypes, suggesting that haplotype structure is influenced by factors other than genetic drift, including both selection and differential haplotype recombination. Knowledge of haplotype-specific LD in the HLA may explain the apparent discrepant data from previous studies of global LD, help delineate key areas in mapping HLA-associated diseases and, together with recombination data, provide valuable information about a population's demographic history and the selective pressures operating on it.
Ahmad
Tariq
T
Gastroenterology Unit, University of Oxford, Gibson Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE, UK. tariq.ahmad@ndm.ox.ac.uk
Neville
Matt
M
Marshall
Sara E
SE
Armuzzi
Alessandro
A
Mulcahy-Hawes
Kim
K
Crawshaw
Jonathan
J
Sato
Hiroe
H
Ling
Khoon-Lin
KL
Barnardo
Martin
M
Goldthorpe
Sue
S
Walton
Robert
R
Bunce
Mike
M
Jewell
Derek P
DP
Welsh
Ken I
KI
D000483:Alleles; D017920:Antiporters / Q000235:genetics; D002874:Chromosome Mapping; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D026901:Membrane Transport Proteins; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
D017920:Antiporters; D015234:HLA-A Antigens; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C107762:tapasin