title: Polymorphism analysis of the huntingtin gene in Italian families affected with Huntington disease.
abstract: Two sources of variation in the huntingtin gene, the length of the CCG-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 chromosomes of 80 Italian families affected with HD. No instances of meiotic instability of the CCG-rich segment were detected. A strong linkage disequilibrium was found between the HD mutation and alleles at both polymorphic regions: CCG-rich length alleles different from 176 bp are underrepresented while delta 2642 is overrepresented on HD chromosomes. The presence of such alleles on HD chromosomes does not affect age at onset of the disease. Normal chromosomes displayed a non-random association, shorter (CAG)n segments being preferentially followed by longer CCG-rich segments. Finally, the finding, among normal subjects, of carriers of variants on both chromosomes denotes that variation at either of the two polymorphisms does not impair the function of the huntingtin gene product.
authors.affiliation: Dipartimento di Biologia, Università di Roma, Tor Vergata, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Novelletto
authors.forename: F
authors.initials: F
authors.lastname: Persichetti
authors.forename: G
authors.initials: G
authors.lastname: Sabbadini
authors.forename: P
authors.initials: P
authors.lastname: Mandich
authors.forename: E
authors.initials: E
authors.lastname: Bellone
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: F
authors.initials: F
authors.lastname: Squitieri
authors.forename: G
authors.initials: G
authors.lastname: Campanella
authors.forename: A
authors.initials: A
authors.lastname: Bozza
authors.forename: M E
authors.initials: ME
authors.lastname: MacDonald
mesh_terms: D000328:Adult; D017668:Age of Onset; D003062:Codon / Q000235:genetics; D005796:Genes; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008875:Middle Aged; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: D003062:Codon; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins