High-Density SNP genotyping defines 17 distinct haplotypes of the TNF block in the Caucasian population: Implications for haplotype tagging†‡
Corresponding Author
Richard J. N. Allcock
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
School of Surgery and Pathology, University of Western Australia, QEII Medical Centre, Monash Avenue, Nedlands 6009, Western AustraliaSearch for more papers by this authorLydia Windsor
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Search for more papers by this authorRamon Kucharzak
Centre National de Génotypage, Evry, France
Department of Biology, Chemistry, and Pharmacy, Berlin Free University, Berlin, Germany
Search for more papers by this authorJean-Guillaume Garnier
Centre National de Génotypage, Evry, France
Search for more papers by this authorFrank T. Christiansen
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia
Search for more papers by this authorPatricia Price
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia
Search for more papers by this authorCorresponding Author
Richard J. N. Allcock
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
School of Surgery and Pathology, University of Western Australia, QEII Medical Centre, Monash Avenue, Nedlands 6009, Western AustraliaSearch for more papers by this authorLydia Windsor
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Search for more papers by this authorRamon Kucharzak
Centre National de Génotypage, Evry, France
Department of Biology, Chemistry, and Pharmacy, Berlin Free University, Berlin, Germany
Search for more papers by this authorJean-Guillaume Garnier
Centre National de Génotypage, Evry, France
Search for more papers by this authorFrank T. Christiansen
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia
Search for more papers by this authorPatricia Price
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia
Search for more papers by this authorCommunicated by Christopher Mathew
The Supplementary Material referred to in this article can be viewed at www.interscience.wiley.com/jpages/1059-7794/suppmat
Abstract
The region spanning the tumor necrosis factor (TNF) cluster in the human major histocompatibility complex (MHC) has been implicated in susceptibility to numerous immunopathological diseases, including type 1 diabetes mellitus and rheumatoid arthritis. However, strong linkage disequilibrium across the MHC has hampered the identification of the precise genes involved. In addition, the observation of “blocks” of DNA in the MHC within which recombination is very rare, limits the resolution that may be obtained by genotyping individual SNPs. Hence a greater understanding of the haplotypes of the block spanning the TNF cluster is necessary. To this end, we genotyped 32 human leukocyte antigen (HLA)-homozygous workshop cell lines and 300 healthy control samples for 19 coding and promoter region SNPs spanning 45 kb in the central MHC near the TNF genes. The workshop cell lines defined 11 SNP haplotypes that account for approximately 80% of the haplotypes observed in the 300 control individuals. Using the control individuals, we defined a further six haplotypes that account for an additional 10% of donors. We show that the 17 haplotypes of the “TNF block” can be identified using 15 SNPs. Hum Mutat 24:517–525, 2004. © 2004 Wiley-Liss, Inc.
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