I. Silveira, I. Alonso, L. Guimarães, P. Mendonça, C. Santos, P

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High Germinal Instability of the (CTG)n at the SCA8 Locus of Both Expanded and Normal Alleles I. Silveira, I. Alonso, L. Guimarães, P. Mendonça, C. Santos, P. Maciel, J.M. Fidalgo de Matos, M. Costa, C. Barbot, A. Tuna, J. Barros, L. Jardim, P. Coutinho, J. Sequeiros The American Journal of Human Genetics Volume 66, Issue 3, Pages 830-840 (March 2000) DOI: 10.1086/302827 Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigrees and genotyping from four families with SCA8. Circles and squares with black dots indicate asymptomatic carriers of expanded alleles. Haplotypes of four microsatellite markers spanning 2 cM within the SCA8-locus region are shown. The haplotype that segregates with the expansion is boxed, and inferred haplotypes are bracketed. The (CTG)n (position unknown) was arbitrarily positioned as being telomeric to all markers. The fifth family (BR) is not shown, since no family genotyping was available. The American Journal of Human Genetics 2000 66, 830-840DOI: (10.1086/302827) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 2 Pedigree and PCR products of family CH. Genomic DNA was amplified by use of primers SCA8-F4 and SCA8-R4. PCR products were analyzed on 6% polyacrylamide gels. Allele sizes were determined by comparison of migration relative to an M13 sequencing ladder. Normal alleles had sizes varying from 15 to 91 units, and expanded alleles varied from 100 to 170. The American Journal of Human Genetics 2000 66, 830-840DOI: (10.1086/302827) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 3 Distribution of CTG repeat size of alleles at the SCA8 locus in a normal population of Portuguese origin (n=1,818). The American Journal of Human Genetics 2000 66, 830-840DOI: (10.1086/302827) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 4 Low-copy PCR of sperm cells. DNA was amplified with primers SCA8-F4 and SCA8-R4 and analyzed on 6% polyacrylamide gels. Allele sizes were determined by comparison of migration relative to a M13 sequencing ladder. A, Patient with alleles of 152 and 28 repeats in peripheral blood; alleles with ≤37 CTGs were assumed to have derived from the 28-repeat allele. B, Healthy control, homozygote for a 25-repeat allele on blood leukocytes; similar results (not shown) were obtained with another healthy control with 25/23 CTGs in peripheral leukocytes. The American Journal of Human Genetics 2000 66, 830-840DOI: (10.1086/302827) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 5 A, Frequency of variation in repeat size of a 152-repeat SCA8 allele in sperm cells of a heterozygous patient with 152/28 CTGs; the arrow indicates the length of the donor’s allele in peripheral blood leukocytes (alleles with ≤37 CTGs are not shown, since they were assumed to be derived from the 28-repeat allele). B, Distribution of repeat-size changes during meiosis (determined by subtracting the size of repeats in leukocytes to that in sperm). The American Journal of Human Genetics 2000 66, 830-840DOI: (10.1086/302827) Copyright © 2000 The American Society of Human Genetics Terms and Conditions