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Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation

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Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2 cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p < 0.001). The most frequent expanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome.

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Acknowledgements

The authors are grateful to patients and their families as well as healthy individuals for providing biological material for this study. We would also like to thank Vanessa Paixão-Côrtes, Nelson Jurandi Rosa Fagundes, and Virginia Ramallo for their contribution in this study.

Funding

This research was supported by Brazilian Funding Agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundo de Incentivo a Pesquisa e Eventos do HCPA (FIPE-HCPA).

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Authors and Affiliations

  1. Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Giovana B. Bampi, Tailise C. Gheno, Gabriel V. Furtado, Maria Cátira Bortolini, Laura B. Jardim & Maria Luiza Saraiva-Pereira

  2. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

    Giovana B. Bampi, Tailise C. Gheno, Gabriel V. Furtado, Laura B. Jardim & Maria Luiza Saraiva-Pereira

  3. Laboratory of Genetics Identification – Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Giovana B. Bampi, Tailise C. Gheno, Gabriel V. Furtado, Laura B. Jardim & Maria Luiza Saraiva-Pereira

  4. Centro Universitario de Tacuarembó, Universidad de la República, Tacuarembó, Uruguay

    Rafael Bisso-Machado

  5. Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil

    Tábita Hünemeier

  6. Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru

    Diego Veliz-Otani, Mario Cornejo-Olivas & Pillar Mazzeti

  7. Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Laura B. Jardim

  8. Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Maria Luiza Saraiva-Pereira

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  1. Giovana B. Bampi
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Bampi, G.B., Bisso-Machado, R., Hünemeier, T. et al. Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation. Neuromol Med 19, 501–509 (2017). https://doi.org/10.1007/s12017-017-8464-8

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