Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus

Hum Genet. 2006 Apr;119(3):255-66. doi: 10.1007/s00439-005-0111-z. Epub 2006 Jan 20.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Computer Simulation
  • Databases, Genetic
  • Demography
  • Genes, T-Cell Receptor alpha*
  • Genes, T-Cell Receptor delta*
  • Genetic Variation*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium*
  • Polymorphism, Single Nucleotide
  • Selection, Genetic*
  • Sequence Analysis, DNA