Disequilibrium patterns of the peptide transporter loci within the HLA class II region

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

DOI:https://doi.org/10.1016/0198-8859(94)91753-1· OSTI ID:133908

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

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1. Univ. of California, Frederick, MD (United States)

Disequilibrium between genetic markers is expected to decline monotonically with recombinational map distance. We present evidence from the HLA class II region which seems to violate this principle. Pairwise disequilibrium values from a sample of northern Europeans were calculated for six loci ranging in physical separation from 7 kb to 550 kb. The histocompatibility loci DRB1, DQA1 and DQB1 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 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. This evidence suggests either a high rate of gene conversion in the TAP loci which mixes TAP alleles among haplotypes while maintaining the flanking markers, or recombinational hot spots near and between the TAP loci operating in combination with selection to preserve particular combinations of alleles at the flanking histocompatibility loci. Whatever explanation proves correct, this work demonstrates that the lack of association of TAP alleles with a DR-DQ associated disease cannot be used as evidence for a centromeric boundary of influence on that disease.

• Sponsoring Organization: USDOE
• OSTI ID: 133908
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

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