Molecular and Clinical Study of 18 Families with ADCA Type II: Evidence for Genetic Heterogeneity and De Novo Mutation P. Giunti, G. Stevanin, P.F. Worth,

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Molecular and Clinical Study of 18 Families with ADCA Type II: Evidence for Genetic Heterogeneity and De Novo Mutation P. Giunti, G. Stevanin, P.F. Worth, G. David, A. Brice, N.W. Wood The American Journal of Human Genetics Volume 64, Issue 6, Pages 1594-1603 (June 1999) DOI: 10.1086/302406 Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigrees of VN, PT, and WI families. Solid symbols denote affected status. The pedigrees have been altered by changing birth order and by substituting diamond symbols for some individuals of both sexes. Haplotypes for chromosome 3p markers are shown. Boxed haplotypes cosegregate with the expanded and intermediate CAG repeats. Boldface numerals denote number of CAG repeats. Dashes are used when alleles could not be typed or deduced. The American Journal of Human Genetics 1999 64, 1594-1603DOI: (10.1086/302406) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 2 Distribution of CAG-repeat numbers in 1,054 independent normal chromosomes from control subjects, spouses, and affected subjects. Two ranges are evident: the first, 7–19, represents the true normal range, and the second, 28–35, represents intermediate alleles (see text). The American Journal of Human Genetics 1999 64, 1594-1603DOI: (10.1086/302406) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 3 Distribution of repeat numbers of 55 chromosomes from patients and 7 from at-risk subjects The American Journal of Human Genetics 1999 64, 1594-1603DOI: (10.1086/302406) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 4 Correlation between the number of SCA7 CAG repeats and age at onset in years. The linear regression line has been applied without including the two largest alleles, as these skew the slope disproportionately. The American Journal of Human Genetics 1999 64, 1594-1603DOI: (10.1086/302406) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 5 Difference in CAG-repeat instability between 14 mother-child pairs and 17 father-child pairs. Only positive values, representing an increase in CAG repeats during transmission, are shown for both sexes. The largest increases occur during paternal transmission. The American Journal of Human Genetics 1999 64, 1594-1603DOI: (10.1086/302406) Copyright © 1999 The American Society of Human Genetics Terms and Conditions