Pascal Jézéquel

Allele frequencies of hereditary hemochromatosis gene mutations in a local population of west Brittany

Abstract Hereditary hemochromatosis (HH) gene mutations, C282Y and H63D, have been screened in a cohort of 254presumably healthy persons originating from a western region of France.The carrier frequencies of these mutations and the incidence of HH have been estimated and compared with those of other studies. This cohort contains two C282Y/C282Y genotypes and has the highest C282Y heterozygosity frequency (17.46%) ever reported.

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

Using a positional cloning strategy to identify the hemochromatosis gene (HFE), we isolated seven cDNAs by cDNA selection from a region of 400 kilobases (kb) located near theHLA-A andHLA-F loci. In this paper, we report the study of one of the corresponding genes, referred to asHCG V (hemochromatosis candidate gene), localized 150 kb centromeric toHLA-A. This gene was found to be expressed ubiquitously in the form of a 1.8 kb transcript, and to be apparently well conserved during evolution. 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 frame of 378 bp, encoding for a 126 amino acid polypeptide which displayed a strong identity with the predicted product of a mouseTctex-5 gene (t complex, testis expressed) localized in the t complex on chromosome 17. TheHCG V gene was assessed as a potential candidate for hemochromatosis in regard to its localization in the linkage disequilibrium area betweenHFE and polymorphic markers. The study of deletions and point mutations in hemochromatosis patients revealed a single bp polymorphism within the coding region; however, no associated disease changes were found. Therefore we chnolade thatHCG V is unlikely to be involved in the pathogenesis of hemochromatosis.

Analysis of 160 CF chromosomes: detection of a novel mutation in exon 20.

The cystic fibrosis (CF) gene has been cloned and a major mutation identified (ΔF508). This 3-bp deletion has been found in approximately 70% of CF chromosomes. We have used the strategy of denaturing gradient gel electrophoresis followed by direct sequencing of the polymerase chain reaction products, in order to detect other mutations in exons 10, 11 and 20 of the CF transmembrane conductance regulator gene. A new mutation, F1286-S, was found in exon 20. It involves a nucleotide change of T→C at nucleotide 3989 and changes a phenylalanine into serine at position 1286 of the protein.