title: High-Density SNP genotyping defines 17 distinct haplotypes of the TNF block in the Caucasian population: implications for haplotype tagging.
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.
authors.affiliation: School of Surgery and Pathology, University of Western Australia, QEII Medical Centre, Nedlands, Australia. rallcock@cyllene.uwa.edu.au
authors.forename: Richard J N
authors.initials: RJ
authors.lastname: Allcock
authors.forename: Lydia
authors.initials: L
authors.lastname: Windsor
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.forename: Ramon
authors.initials: R
authors.lastname: Kucharzak
authors.forename: Laetitia
authors.initials: L
authors.lastname: Sobre
authors.forename: Doris
authors.initials: D
authors.lastname: Lechner
authors.forename: Jean-Guillaume
authors.initials: JG
authors.lastname: Garnier
authors.forename: Svetlana
authors.initials: S
authors.lastname: Baltic
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D002461:Cell Line, Transformed; D053487:DEAD-box RNA Helicases; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D048069:Tumor Necrosis Factors; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases