ISOLATION OF CA DINUCLEOTIDE REPEATS CLOSE TO D6S105 - LINKAGE DISEQUILIBRIUM WITH HEMOCHROMATOSIS

The gene for hereditary haemochromatosis (HC) is linked to HLA-A and D6S105 on chromosome 6p. Both markers have also been reported to display linkage disequilibrium with the disease. However, their physical localization relative to one another has not been established. We demonstrate by fluorescent in situ hybridisation that D6S105 lies at least 1-2 Mb telomeric of HLA-A. The haemochromatosis critical region extending from proximal of HLA-A to distal of D6S105 is therefore large. To improve the genetic resolution in this region more highly polymorphic markers are required. We have therefore isolated three novel CA dinucleotide repeats close to D6S105. A linkage disequilibrium study, with two of these microsatellites, in HC patients and controls lends support to the conclusion that D6S105 is a close marker to the haemochromatosis gene.