title: Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus.
abstract: T cell receptors (TR), through their interaction with the major histocompatibility complex, play a central role in immune responsiveness and potentially immune-related disorders. We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent. Two hundred and eighty-four single nucleotide polymorphisms (SNPs) were identified. The distribution of SNPs between V genes was heterogeneous, with an average of five SNPs per gene and a range of zero to 15. We describe the patterns of linkage disequilibrium for these newly discovered SNPs and compare these patterns with other emerging large-scale datasets (e.g. Perlegen and HapMap projects) to place our findings into a framework for future analysis of genotype-phenotype associations across this locus. Furthermore, we explore signatures of natural selection across V genes. We find evidence of strong directional selection at this locus as evidenced by unusually high values of Fst.
authors.affiliation: Department of Genome Sciences, University of Washington, 357730, Seattle, WA, 98195-7730, USA. rmack@u.washington.edu
authors.forename: Rachel
authors.initials: R
authors.lastname: Mackelprang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Livingston
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eberle
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Qian
authors.initials: Q
authors.lastname: Yi
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
mesh_terms: D003198:Computer Simulation; D030541:Databases, Genetic; D003710:Demography; D019673:Genes, T-Cell Receptor alpha; D019676:Genes, T-Cell Receptor delta; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA