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Published June 1, 1990 | Published
Journal Article Open

Haplotyping the human T-cell receptor, β-chain gene complex by use of restriction fragment length polymorphisms

Abstract

We have studied the genetic segregation of human T-cell receptor beta-chain (TCR beta) genes on chromosome 7q in 40 CEPH (Centre d'Etude du Polymorphisme Humain) families by using restriction fragment length polymorphisms (RFLPs). We constructed haplotypes from eight RFLPs by using variable- and constant-region cDNA probes, which detect polymorphisms that span more than 600 kilobases of the TCR beta gene complex. Analysis of allele distributions between TCR beta genes revealed significant linkage disequilibrium between only 6 of the 28 different pairs of RFLPs. This linkage disequillibrium strongly influences the most efficient order to proceed for typing of these RFLPs in order to achieve maximum genetic informativeness, which in this study revealed a 97.3% level of heterozygosity within the TCR beta gene complex. Our results should provide new insight into recent reports of disease associations with the TCR beta gene complex and should assist in designing future experiments to detect or confirm the existence of disease-susceptibility loci in this region of the human genome.

Additional Information

© 1990 National Academy of Sciences. Contributed by Leroy Hood, April 17, 1990. We gratefully acknowledge J. Tillinghast and T. Mak for supplying DNA probes. We appreciate the technical assistance of W. Shan and J. Nguyen. This work was supported by National Research Service Award GM07104 from the U.S. Public Health Service to P. Charmley and by grants from the American Cancer Society, T-cell Sciences, the Siever Foundation, the U.S. Department of Energy, and the Ataxia-Telangiectasia Medical Research Foundation. R.A.G. is a member of the Jonsson Comprehensive Cancer Center.

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