POLYMORPHISM ANALYSIS OF THE HUNTINGTIN GENE IN ITALIAN FAMILIES AFFECTED WITH HUNTINGTON DISEASE

Two sources of variation in the huntingtin gene, the length of the COO -rich segment downstream to the (CAG)(n) stretch undergoing expansion in Huntington disease (HD) and the deletion of 3 bp at codon positions 2642 - 2645 (Delta 2642), were analysed on the normal and HD chromoso mes of 80 Italian families affected with HD. No instances of meiotic i nstability of the CCG-rich segment were detected. A strong linkage dis equilibrium was found between the HD mutation and alleles at both poly morphic regions: CCG-rich length alleles different from 176 bp are und errepresented while Delta 2642 is overrepresented on HD chromosomes. T he presence of such alleles on HD chromosomes does not affect age at o nset of the disease. Normal chromosomes displayed a non-random associa tion, shorter (CAG)(n) segments being preferentially followed by longe r CCG-rich segments. Finally, the finding, among normal subjects, of c arriers of variants on both chromosomes denotes that variation at eith er of the two polymorphisms does not impair the function of the huntin gtin gene product.