title: Structure of tumor necrosis factor-alpha haploblocks in European populations.
abstract: DNA variants in the tumor necrosis factor-α (TNF) and linked lymphotoxin-α genes, and specific alleles of the highly polymorphic human leukocyte antigen B (HLA-B) gene have been implicated in a plethora of immune and infectious diseases. However, the tight linkage disequilibrium characterizing the central region of the human major histocompatibility complex (MHC) containing these gene loci has made difficult the unequivocal interpretation of genetic association data. To alleviate these difficulties and facilitate the design of more focused follow-up studies, we investigated the structure and distribution of HLA-B-specific MHC haplotypes reconstructed in a European population from unphased genotypes at a set of 25 single nucleotide polymorphism sites spanning a 66-kilobase long region across TNF. Consistent with the published data, we found limited genetic diversity across the so-called TNF block, with the emergence of seven common MHC haplotypes, termed TNF block super-haplotypes. We also found that the ancestral haplotype 8.1 shares a TNF block haplotype with HLA-B*4402. HLA-B*5701, a known protective allele in HIV-1 pathogenesis, occurred in a unique TNF block haplotype.
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, AL, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Merino
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Brahim
authors.initials: B
authors.lastname: Aissani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015235:HLA-B Antigens; D000949:Histocompatibility Antigens Class II; C478969:MCCD1 protein, human; D024101:Mitochondrial Proteins; C120111:NFKBIL1 protein, human; D014409:Tumor Necrosis Factor-alpha; C506469:ATP6V1G2 protein, human; C487886:DDX39B protein, human; D025262:Vacuolar Proton-Translocating ATPases; D053487:DEAD-box RNA Helicases