Scientific Publications

A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.

Publication TypeJournal Article
Authorsde Bakker, PI, McVean G., Sabeti PC, Miretti MM, Green T., Marchini J., Ke X., Monsuur AJ, Whittaker P., Delgado M., Morrison J., Richardson A., Walsh EC, Gao X., Galver L., Hart J., Hafler DA, Pericak-Vance M., Todd JA, Daly M. J., Trowsdale J., Wijmenga C., Vyse TJ, Beck S., Murray SS, Carrington M., Gregory S., Deloukas P., and Rioux JD
AbstractThe proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
Year of Publication2006
JournalNature genetics
Volume38
Issue10
Pages1166-72
Date Published (YYYY/MM/DD)2006/10/01
ISSN Number1061-4036
DOI10.1038/ng1885
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/16998491?dopt=Abstract