Nature Genetics
- 38, 1166 - 1172 (2006)
Published online: 24 September 2006; | doi:10.1038/ng1885
A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHCPaul I W de Bakker1, 2, 16, Gil McVean3, 16, Pardis C Sabeti1, 16, Marcos M Miretti4, 16, Todd Green1, Jonathan Marchini3, Xiayi Ke5, Alienke J Monsuur6, Pamela Whittaker4, Marcos Delgado4, Jonathan Morrison4, Angela Richardson1, Emily C Walsh1, Xiaojiang Gao7, Luana Galver8, John Hart9, David A Hafler1, 10, Margaret Pericak-Vance9, John A Todd11, Mark J Daly1, 2, John Trowsdale12, Cisca Wijmenga6, Tim J Vyse13, Stephan Beck4, Sarah Shaw Murray8, Mary Carrington7, Simon Gregory9, Panos Deloukas4 & John D Rioux1, 14, 151
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA. 2
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114-2790, USA. 3
Department of Statistics, University of Oxford, Oxford, UK. 4
Wellcome Trust Sanger Institute, Hinxton, UK. 5
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. 6
Complex Genetics Section, Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands. 7
Laboratory of Genomic Diversity, SAIC-Frederick, Inc. and National Cancer Institute–Frederick, Frederick, Maryland, USA. 8
Illumina, Inc., San Diego, California, USA. 9
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA. 10
Center for Neurologic Diseases Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 11
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. 12
Cambridge Institute for Medical Research, Addensbrookes Hospital, Hills Road, Cambridge, UK. 13
Imperial College of London, London, UK. 14
Université de Montréal, Department of Medicine, Montréal, Québec, Canada. 15
Montréal Heart Institute, Montréal, Québec, Canada. 16
These authors contributed equally to this work.
Correspondence should be addressed to John D Rioux rioux@broad.mit.edu The 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 diseases1. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC2,
3. 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.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
