TY - JOUR
T1 - Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus
AU - Mackelprang, Rachel
AU - Livingston, Robert J.
AU - Eberle, Michael A.
AU - Carlson, Christopher S.
AU - Yi, Qian
AU - Akey, Joshua M.
AU - Nickerson, Deborah A.
N1 - Funding Information:
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).
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-005-0111-z
DO - 10.1007/s00439-005-0111-z
M3 - Article
C2 - 16425038
AN - SCOPUS:33644995480
SN - 0340-6717
VL - 119
SP - 255
EP - 266
JO - Human Genetics
JF - Human Genetics
IS - 3
ER -