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

Rachel Mackelprang, Robert J. Livingston, Michael A. Eberle, Christopher S. Carlson, Qian Yi, Joshua M. Akey, Deborah A. Nickerson

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)255-266
Number of pages12
JournalHuman Genetics
Volume119
Issue number3
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Mackelprang, R., Livingston, R. J., Eberle, M. A., Carlson, C. S., Yi, Q., Akey, J. M., & Nickerson, D. A. (2006). Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus. Human Genetics, 119(3), 255-266. https://doi.org/10.1007/s00439-005-0111-z