Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus

Am J Hum Genet. 2001 Aug;69(2):381-95. doi: 10.1086/321297. Epub 2001 Jun 29.


The T-cell receptor (TCR) plays a central role in the immune system, and > 90% of human T cells present a receptor that consists of the alpha TCR subunit (TCRA) and the beta subunit (TCRB). Here we report an analysis of 63 variable genes (BV), spanning 553 kb of TCRB that yielded 279 single-nucleotide polymorphisms (SNPs). Samples were drawn from 10 individuals and represent four populations-African American, Chinese, Mexican, and Northern European. We found nine variants that produce nonfunctional BV segments, removing those genes from the TCRB genomic repertoire. There was significant heterogeneity among population samples in SNP frequency (including the BV-inactivating sites), indicating the need for multiple-population samples for adequate variant discovery. In addition, we observed considerable linkage disequilibrium (LD) (r(2) > 0.1) over distances of approximately 30 kb in TCRB, and, in general, the distribution of r(2) as a function of physical distance was in close agreement with neutral coalescent simulations. LD in TCRB showed considerable spatial variation across the locus, being concentrated in "blocks" of LD; however, coalescent simulations of the locus illustrated that the heterogeneity of LD we observed in TCRB did not differ markedly from that expected from neutral processes. Finally, examination of the extended genotypes for each subject demonstrated homozygous stretches of >100 kb in the locus of several individuals. These results provide the basis for optimization of locuswide SNP typing in TCRB for studies of genotype-phenotype association.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Computer Simulation
  • DNA, Intergenic / genetics
  • Ethnicity / genetics
  • Gene Frequency / genetics
  • Genes, T-Cell Receptor beta / genetics*
  • Genetic Heterogeneity
  • Genetic Variation / genetics*
  • Homozygote
  • Humans
  • Linkage Disequilibrium / genetics*
  • Multigene Family / genetics
  • Mutagenesis / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Racial Groups / genetics


  • DNA, Intergenic