Discordant patterns of linkage disequilibrium of the peptide-transporter loci within the HLA class II region

Journal Article · Fri Dec 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:186215

Klitz, W; Grote, M ^[1]; Stephens, J C ^[2]

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1. Univ. of California, Berkeley, CA (United States)
2. Frederick Cancer Research and Development Center, MD (United States); and others

Disequilibrium between genetic markers is expected to decline monotonically with recombinational map distance. We present evidence from the HLA class II region that seems to violate this principle. Pairwise disequilibrium values were calculated for six loci ranging in physical separation from 15 kb to 550 kb. The histocompatibility loci DRB1, DQA1, and DQBI, located on the distal end of the class II region, behave as a single evolutionary unit within which extremely high linkage disequilibrium exists. Lower but still significant levels of disequilibrium are present between these loci and DPB1, located at the proximal edge of the HLA complex. The peptide-transporter loci TAP1 and TAP2, located in the intervening region, reveal no disequilibrium with each other and low or negligible disequilibrium with the flanking loci. The action of two genetic processes is required to account for this phenomenon: a recombinational hotspot operating between TAP1 and TAP2, to eliminate disequilibrium between these loci, and at the same time selection operating on particular combinations of alleles across the DR-DP region, to create disequilibrium in the favored haplotypes. The forces producing the patterns of disequilibrium observed here have implications for the mapping of trait loci and disease genes: markers of TAP1, for example, would give a false impression as to the influence of DPB1 on a trait known to be associated with DQB1. 44 refs., 2 figs., 3 tabs.

• OSTI ID: 186215
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 6 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
GENE AMPLIFICATION
GENE RECOMBINATION
GENES
GENETIC MAPPING
GENETICS
GENOTYPE
HISTOCOMPATIBILITY COMPLEX
PEPTIDES
STATISTICS