An integrated haplotype map of the human major histocompatibility complex.
Numerous studies have clearly indicated a role for the major histocompatibility complex (MHC) in susceptibility to autoimmune diseases. Such studies have focused on the genetic variation of a small number of classical human-leukocyte-antigen (HLA) genes in the region. Although these genes represent good candidates, given their immunological roles, linkage disequilibrium (LD) surrounding these genes has made it difficult to rule out neighboring genes, many with immune function, as influencing disease susceptibility. It is likely that a comprehensive analysis of the patterns of LD and variation, by using a high-density map of single-nucleotide polymorphisms (SNPs), would enable a greater understanding of the nature of the observed associations, as well as lead to the identification of causal variation. We present herein an initial analysis of this region, using 201 SNPs, nine classical HLA loci, two TAP genes, and 18 microsatellites. This analysis suggests that LD and variation in the MHC, aside from the classical HLA loci, are essentially no different from those in the rest of the genome. Furthermore, these data show that multi-SNP haplotypes will likely be a valuable means for refining association signals in this region.
Walsh
Emily C
EC
Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Mather
Kristie A
KA
Schaffner
Stephen F
SF
Farwell
Lisa
L
Daly
Mark J
MJ
Patterson
Nick
N
Cullen
Michael
M
Carrington
Mary
M
Bugawan
Teodorica L
TL
Erlich
Henry
H
Campbell
Jay
J
Barrett
Jeffrey
J
Miller
Katie
K
Thomson
Glenys
G
Lander
Eric S
ES
Rioux
John D
JD
D002874:Chromosome Mapping; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008285:Major Histocompatibility Complex; D018895:Microsatellite Repeats
D006680:HLA Antigens