A High-Resolution Linkage-Disequilibrium Map of the Human Major Histocompatibility Complex and First Generation of Tag Single-Nucleotide Polymorphisms

摘要: Autoimmune, inflammatory, and infectious diseases present a major burden to human health are frequently associated with loci in the histocompatibility complex (MHC). Here, we report high-resolution (1.9 kb) linkage-disequilibrium (LD) map of 4.46-Mb fragment containing MHC U.S. pedigrees northern western European ancestry collected by Centre d'Etude du Polymorphisme Humain (CEPH) first generation haplotype tag single-nucleotide polymorphisms (tagSNPs) that provide up fivefold increase genotyping efficiency for all future MHC-linked disease-association studies. The data confirm previously identified recombination hotspots class II region allow prediction numerous novel I III regions. longest LD maps outside classic extended spanning olfactory-receptor gene cluster. homozygosity analysis recent positive selection shows 14 outlying variants single haplotype, which most commonly bears HLA-DRB1*1501. SNP data, blocks, tagSNPs reported here have been entered into multidimensional Web-based database (GLOVAR), where they can be accessed viewed context relevant genome annotation. This allowed us give coordinates extremely variable structure underlying MHC.