Conservation of ancestral haplotypes telomeric of HLA-A

Eur J Immunogenet. 1997 Aug;24(4):275-85. doi: 10.1111/j.1365-2370.1997.tb00021.x.

Abstract

Genes that predispose to haemochromatosis are though to be located within the several megabases telomeric of HLA-A. Further recombinant mapping has been used previously to map susceptibility genes for diseases such as insulin-dependent diabetes mellitus, myasthenia gravis and cystic fibrosis, and should be useful in relation to haemochromatosis. However, this method requires the recognition of ancestral haplotypes within the susceptibility region. Using a panel of six microsatellite markers from this region (MOG A, MOG B, MOG C, D6S464, D6S306 and D6S105), we show that ancestral haplotypes extend telomeric of HLA-A, at least as far as D6S105. Nine of 14 haplotypes carrying HLA-B7 and HLA-A3 shared the same microsatellite alleles between HLA-A and at least D6S105. Similarly, nine of 10 haplotypes sharing HLA-B8 and HLA-A1 shared the same microsatellite alleles, although a different set to those with HLA-B7 and HLA-A3. Haplotypes representing historical recombination events were also identified. These two findings demonstrate that recombinant mapping may be applicable to the mapping of disease genes in this region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes
  • Cell Line, Transformed
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 6 / genetics
  • Genes, MHC Class I / genetics*
  • Genetic Predisposition to Disease
  • HLA-A Antigens / genetics*
  • Haplotypes*
  • Humans
  • Microsatellite Repeats
  • Phenotype
  • Recombination, Genetic
  • Telomere / genetics*

Substances

  • HLA-A Antigens