A NEW HIGHLY POLYMORPHIC MARKER IN THE 5'-UNTRANSLATED REGION OF HLA-F SHOWS STRONG ALLELIC ASSOCIATION WITH HEMOCHROMATOSIS

The 5' untranslated region of HLA-F contains a polypurine tract compri sing repeats of tri- and hexa-nucleotide motifs. We have recently demo nstrated that this polypurine tract is highly polymorphic by using the polymerase chain reaction. Here, we demonstrate that some of the alle les can be explained by a deletion of approximately 100 bp DNA and sho w that alleles of this novel, highly polymorphic locus are as strongly associated with haemochromatosis as HLA-A3 or D6S105-8. The observed frequency of heterozygosity at HLA-RF is extremely high (95%) and this locus has been found to be informative in pedigrees that are non-info rmative at HLA-A and D6S105. We also show an example of replication sl ippage at HLA-F in one pedigree.