NEW POLYMORPHISMS AND MARKERS IN THE HLA CLASS-I REGION - RELEVANCE TO HEREDITARY HEMOCHROMATOSIS (HFE)

Hereditary hemochromatosis (HFE) is an inherited disorder whose gene l ies in the proximity of the histocompatability antigen (HLA) class I r egion, on 6p21.3. Despite efforts in refining the HFE region, a number of informative DNA markers, linked to the disease locus and amenable to use in an assay based on the polymerase chain reaction (PCR) is ava ilable. The gene content of this region is high, and the HFE gene has not so far been identified. We have used a strategy based on PCR proto cols potentially able to detect both polymorphisms and expressed seque nces. This approach has been applied to a 700-kb stretch (approximatel y) of DNA corresponding to the insert of a Centre d'Etude du Polymorph isme Humain yeast artificial chromosome (225 B1) of the possible candi date region. Five new polymorphisms have been detected among 20 specif ic fragments isolated. Four of them are tightly linked to the HFE locu s. Because of the strong linkage disequilibrium with the disease demon strated by these markers, they could represent starting points for the identification and characterization of the HFE gene. The remaining no n-polymorphic fragments, being amplifiable and in most cases linked to NotI sites, may be useful starting points for the generation of a gen omic contig of band 6p21.3 and for gene identification.