A High-Resolution Linkage-Disequilibrium Map of the Human Major Histocompatibility Complex and First Generation of Tag Single-Nucleotide Polymorphisms
| Autor: | Panos Deloukas, David R. Bentley, Stephan Beck, John D. Rioux, Emily C. Walsh, Xiayi Ke, Jonathan Morrison, Eric S. Lander, Pamela Whittaker, Marcos Delgado, Mark Griffiths, Sarah E. Hunt, Marcos Mateo Miretti, Lon R. Cardon |
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| Rok vydání: | 2005 |
| Předmět: |
Linkage disequilibrium
Population Context (language use) Single-nucleotide polymorphism Major histocompatibility complex Polymorphism Single Nucleotide Linkage Disequilibrium Major Histocompatibility Complex 03 medical and health sciences 0302 clinical medicine Genetics Humans Genetics(clinical) education Genetics (clinical) 030304 developmental biology Recombination Genetic 0303 health sciences education.field_of_study biology Haplotype Articles Genome project 3. Good health Haplotypes biology.protein Human genome 030215 immunology |
| Zdroj: | The American Journal of Human Genetics. 76:634-646 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/429393 |
| Popis: | Autoimmune, inflammatory, and infectious diseases present a major burden to human health and are frequently associated with loci in the human major histocompatibility complex (MHC). Here, we report a high-resolution (1.9 kb) linkage-disequilibrium (LD) map of a 4.46-Mb fragment containing the MHC in U.S. pedigrees with northern and western European ancestry collected by the Centre d'Etude du Polymorphisme Humain (CEPH) and the first generation of haplotype tag single-nucleotide polymorphisms (tagSNPs) that provide up to a fivefold increase in genotyping efficiency for all future MHC-linked disease-association studies. The data confirm previously identified recombination hotspots in the class II region and allow the prediction of numerous novel hotspots in the class I and class III regions. The region of longest LD maps outside the classic MHC to the extended class I region spanning the MHC-linked olfactory-receptor gene cluster. The extended haplotype homozygosity analysis for recent positive selection shows that all 14 outlying haplotype variants map to a single extended haplotype, which most commonly bears HLA-DRB1*1501. The SNP data, haplotype blocks, and tagSNPs analysis reported here have been entered into a multidimensional Web-based database (GLOVAR), where they can be accessed and viewed in the context of relevant genome annotation. This LD map allowed us to give coordinates for the extremely variable LD structure underlying the MHC. |
| Databáze: | OpenAIRE |
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