Localization of the hemochromatosis gene close to D6S105
- Queensland Institute of Medical Research, Brisbane (Australia)
The hemochromatosis (HC) gene is known to be linked to HLA-A (6p21.3); however, its precise location has been difficult to determine because of a lack of additional highly polymorphic markers for this region. The recent identification of short tandem repeat sequences (microsatellites) has now provided this area with a number of markers with similar polymorphic index to the HLA serological polymorphisms. Using four microsatellites - D6S105, D6S109, D6S89, and F13A - together with the HLA class I loci HLA-A and HLA-B in 13 large pedigrees clearly segregating for HC, the authors have been able to refine the location of the HC gene. They identified no recombination between HC and HLA-A or D6S105, and two-point analyses placed the HC gene within one centimorgan (cM) of HLA-A and D6S105. The markers HLA-B, D6S109, D6S89, and F13A were separated from the HC locus by recombination, defining the centromeric and telomeric limits for the HC gene as HLA-B and D5S109, respectively. A multipoint map constructed using HLA-B, HLA-A, and D6S109 indicates that the HC gene is located in a region less than 1 cM proximal to HLA-A and less than 1 cM telomeric of HLA-A. These pedigree data indicate an association between HC and specific alleles at HLA-A and D6S105 (i.e., HLA-A3 and D6S105 allele 8). To determine the significance of these allelic associations, the authors have analyzed the allele's frequency in 82 unrelated HC patients and 82 unrelated healthy controls. D6S105 allele 8 was present in 93% of patients and only 21% of controls ([chi][sup 2] = 86.46; P < .0001). The approximate relative risk for this allele was 48.4 HLA-A3 was present in 62% of patients and 26% of controls ([chi][sup 2] = 22.28; P<.001). Approximate relative risk for A3 was 4.8. They conclude that the microsatellite marker D6S105 is the closest marker to the HC gene reported to date. 26 refs., 1 fig., 3 tabs.
- OSTI ID:
- 5914608
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 53:2; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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