CLONING OF A HUMAN HOMOLOG OF THE MOUSE TCTEX-5 GENE WITHIN THE MHC CLASS-I REGION

Using a positional cloning strategy to identify the hemochromatosis ge ne (HFE), we isolated seven cDNAs by cDNA selection from a region of 4 00 kilobases (kb) located near the HLA-A and HLA-F loci. In this paper , we report the study of one of the corresponding genes, referred to a s HCG V (hemochromatosis candidate gene), localized 150 kb centromeric to HLA-A. This gene was found to be expressed ubiquitously in the for m of a 1.8 kb transcript, and to be apparently well conserved during e volution. The gene spanned 3.1 kb and is organized in three exons and two introns. The cDNA of 1620 base pairs (bp) showed an open reading f rame of 378 bp, encoding for a 126 amino acid polypeptide which displa yed a strong identity with the predicted product of a mouse Tctex-5 ge ne (t complex, testis expressed) localized in the t complex on chromos ome 17. The HCG V gene was assessed as a potential candidate for hemoc hromatosis in regard to its localization in the linkage disequilibrium area between HFE and polymorphic markers. The study of deletions and point mutations in hemochromatosis patients revealed a single bp polym orphism within the coding region; however, no associated disease chang es were found, Therefore we conclude that HCG Vis unlikely to be invol ved in the pathogenesis of hemochromatosis.