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Selective Forces Related to Spinocerebellar Ataxia Type 2

  • Lucas Schenatto Sena
  • Raphael Machado Castilhos
  • Eduardo Preusser Mattos
  • Gabriel Vasata Furtado
  • José Luiz Pedroso
  • Orlando Barsottini
  • Maria Marla Paiva de Amorim
  • Clecio Godeiro
  • Maria Luiza Saraiva Pereira
  • Laura Bannach Jardim
Original Paper
  • 44 Downloads

Abstract

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.

Keywords

Anticipation CAG repeats Reproductive success Segregation distortion SCA2 Spinocerebellar ataxia type 2 

Notes

Acknowledgements

The authors would like to thank the individuals who agreed to participate in this study.

Funding Information

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.

Supplementary material

12311_2018_977_Fig3_ESM.png (91 kb)
Supplemental Figure 1

- 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)

12311_2018_977_MOESM1_ESM.tif (325 kb)
High resolution image (TIF 325 kb)
12311_2018_977_Fig4_ESM.png (72 kb)
Supplemental Figure 2

- 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)

12311_2018_977_MOESM2_ESM.tif (1.4 mb)
High resolution image (TIF 1424 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lucas Schenatto Sena
    • 1
  • Raphael Machado Castilhos
    • 2
  • Eduardo Preusser Mattos
    • 1
    • 7
  • Gabriel Vasata Furtado
    • 1
    • 7
  • José Luiz Pedroso
    • 3
  • Orlando Barsottini
    • 3
  • Maria Marla Paiva de Amorim
    • 4
  • Clecio Godeiro
    • 4
  • Maria Luiza Saraiva Pereira
    • 1
    • 5
    • 6
    • 7
  • Laura Bannach Jardim
    • 1
    • 5
    • 7
    • 8
  1. 1.Programa de Pós-Graduação em Genética e Biologia MolecularUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Serviço de NeurologiaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Setor de Neurologia Geral e Ataxias. Disciplina de Neurologia Clínica da UNIFESP – Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Universidade Federal do Rio Grande do NorteNatalBrazil
  5. 5.Serviço de Genética MédicaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  6. 6.Departamento de BioquímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  7. 7.Laboratório de Identificação Genética, Centro de Pesquisa ExperimentalHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  8. 8.Departamento de Medicina InternaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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