Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation, SCA2 frequency seems to be stable in populations. Our aim was to estimate reproductive success, segregation patterns, and role of anticipation in SCA2. Adult subjects from families with molecular diagnosis provided data about all his/her relatives. Affected and unaffected sibs older than 65.7 years of age were used to estimate reproductive success and segregation patterns. Twenty-one SCA2 families were studied, including 1017 individuals (164 affected) who were born from 1840 to 2012. The median number of children of the non-carriers and carriers, among 99 subjects included in the reproductive success analysis, were 2 and 3 (p < 0.025), respectively. Therefore, the reproductive success of carriers was 1.5. There were 137 non-carriers (59.6%) and 93 carriers (40.4%) (p = 0.04), among subjects included in the segregation analysis. Age at onset across generations pointed to anticipation as a frequent phenomenon. We raised evidence in favor of increased reproductive success related to the carrier state at ATXN2, and segregation distortion favoring normal alleles. Since majority of normal alleles analyzed carried 22 repeats, we propose that this distortion segregation can be related to the high frequency of this allele in human chromosomes.
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The authors would like to thank the individuals who agreed to participate in this study.
This work was supported by FIPE-HCPA – Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre – Project GPPG HCPA 16-320. EPM, GVF, MLSP and LBJ were supported by CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- Histogram showing the relationship between the children’s year of birth and year of onset of symptoms in the affected parent. Onset of symptoms is represented by “0” (zero), negative numbers represent the number of years before the onset of symptoms, while positive numbers represent the number of years after the onset of symptoms in the affected parent. (PNG 90 kb)
- Histogram describing the differences between ages at onset (delta-AO) of the affected individuals and their transmitting parents. Transmitting fathers were depicted as male transmissions; those of mothers were depicted as female transmissions. (PNG 72 kb)
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