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Analysis of (CAG)n size heterogeneity in somatic and sperm cell DNA from intermediate and expanded Huntington disease gene carriers
Author(s) -
Giovan Barbara,
Sabbadini Guglielmo,
Di Maio Luigi,
Calabrese Olga,
Castaldo Imma,
Frontali Marina,
Novelletto Andrea,
Squitieri Ferdinando
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:6<458::aid-humu7>3.0.co;2-9
Subject(s) - biology , somatic cell , sperm , genetics , proband , gene , genome instability , allele , chromosome instability , germline mosaicism , x chromosome , chromosome , dna , microbiology and biotechnology , mutation , dna damage
The length of the CAG repeat responsible for Huntington disease has been analysed by two PCR methods in blood and sperm DNA of 13 expansion carriers, two carriers of intermediate alleles, and four normal subjects. The two methods consistently confirmed size heterogeneity, more pronounced in sperm and confined to the CAG stretch. Based on densitometric scanning of films, four indexes addressed to different features of the PCR pattern were used to quantitate mosaicism. These revealed strong correlations with CAG size and intergenerational instability. However, mosaicism did not show a greater similarity in sibs who shared the same HD chromosome, nor was correlated with instability in the proband's pedigree. Our data do not support the hypothesis that cis ‐acting factors play a major role in the instability and leave the CAG size per se as the major determinant of sperm cell CAG instability. Hum Mutat 10:458–464, 1997. © 1997 Wiley‐Liss, Inc.