Conservation of ancestral haplotypes telomeric of HLA-A.
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.
Tay
G K
GK
Centre for Molecular Immunology and Instrumentation, University of Western Australia, Royal Perth Hospital, Perth, Western Australia.
Cattley
S K
SK
Chorney
M J
MJ
Hollingsworth
P N
PN
Roth
M P
MP
Dawkins
R L
RL
Witt
C S
CS
D001402:B-Lymphocytes; D002461:Cell Line, Transformed; D002874:Chromosome Mapping / Q000379:methods; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005805:Genes, MHC Class I / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D010641:Phenotype; D011995:Recombination, Genetic; D016615:Telomere / Q000235:genetics*
D015234:HLA-A Antigens