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

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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 F st

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Acknowledgements

We thank M. Rieder and L. Subrahmanyan for many helpful discussions, and S. daPonte and M. Montoya for their assistance in obtaining the TR polymorphisms. This work was accomplished with support from the National Institutes of Health (NIH) (AI45279) and a Program for Genomic Application (HL66682) to DAN and support to RM from the NIH (T32 HG-000035).

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  1. Department of Genome Sciences, University of Washington, 357730, Seattle, WA, 98195-7730, USA

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

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  1. Rachel Mackelprang
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  2. Robert J. Livingston
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  3. Michael A. Eberle
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  7. Deborah A. Nickerson
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Correspondence to Rachel Mackelprang.

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Mackelprang, R., Livingston, R.J., Eberle, M.A. et al. Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus. Hum Genet 119, 255–266 (2006). https://doi.org/10.1007/s00439-005-0111-z

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