Comprehensive Genetic Variant Mapping in MHC

SNPs and DIPs were identified from the MHC Haplotype Project, dbSNP, and dbMHC databases and selected based on their genomic position. SNPs were typed on the Illumina GoldenGate platform at the Broad Institute of MIT and Harvard, at Illumina, and at the Wellcome Trust Sanger Institute or by using using TaqMan Allelic Discrimination Assay at Duke University. Insertion/deletion polymorphisms were typed by TaqMan technology at Duke University. All of the SNP, DIP and HLA typing was completed by June 2005 and preceded the release of Phase II data from the International HapMap Project. The entire list of 7,543 non-redundant variants and their respective genotyping assays are available online (see below). The variants were located in the 7.5 Mb region delimited by rs498548 (position chr6:26000508) and rs2772390 (position chr6:33483033). All coordinates are given relative to NCBI build 34 of the human genome assembly. Raw genotype data collected at the various genotyping centers were collated based on map position. A total of 6,338 variants yielded reliable genotyping assays. Assays considered to be reliable yielded at least 90% total genotypes, fewer than two Mendel errors, and were in Hardy-Weinberg equilibrium (P > 0.001). Details of how haplotypes were estimated from genotype data can be found in Supplementary Note online.

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de Bakker P.I., Mcvean G., Sabeti P.C., Miretti M.M., Green T., Marchini J., Ke X., Monsuur A.J., Whittaker P., Delgado M., Morrison J., Richardson A., Walsh E.C., Gao X., Galver L., Hart J., Hafler D.A., Pericak-Vance M., Todd J.A., Daly M.J., Trowsdale J., Wijmenga C., Vyse T.J., Beck S., Murray S.S., Carrington M., Gregory S., Deloukas P, & Rioux J.D. (2006). A high resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nature genetics, 38(10), 1166-1172.

Publication 2006

A 338 Allelic Assays Dips Discrimination Genomic Genotype Haplotypes Human genome Insertion deletion Polymorphisms

Corresponding Organization : Université de Montréal

Other organizations : Broad Institute, University of Oxford, Wellcome Sanger Institute, Wellcome Centre for Human Genetics, University Medical Center Utrecht, Science Applications International Corporation (United States), National Cancer Institute, Illumina (United States), Duke University Hospital, Duke Medical Center, Center for Human Genetics, Brigham and Women's Hospital, Harvard University, Juvenile Diabetes Research Foundation, University of Cambridge, Wellcome Trust, Massachusetts General Hospital, Addenbrooke's Hospital, Imperial College London

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Variable analysis

independent variables

SNPs and DIPs identified from the MHC Haplotype Project, dbSNP, and dbMHC databases
SNP typing method (Illumina GoldenGate platform, TaqMan Allelic Discrimination Assay)
Insertion/deletion polymorphism typing method (TaqMan technology)

dependent variables

Genotypes of the 7,543 non-redundant variants

control variables

Genomic position of the variants (located in the 7.5 Mb region delimited by rs498548 and rs2772390)
Variant filtering criteria (yielded at least 90% total genotypes, fewer than two Mendel errors, and were in Hardy-Weinberg equilibrium (P > 0.001))
Timing of genotyping (completed by June 2005, preceding the release of Phase II data from the International HapMap Project)

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