Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10).
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was so...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2639644?pdf=render |
| _version_ | 1818273916799418368 |
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| author | Teresa Almeida Isabel Alonso Sandra Martins Eliana Marisa Ramos Luísa Azevedo Kinji Ohno António Amorim Maria Luiza Saraiva-Pereira Laura Bannach Jardim Tohru Matsuura Jorge Sequeiros Isabel Silveira |
| author_facet | Teresa Almeida Isabel Alonso Sandra Martins Eliana Marisa Ramos Luísa Azevedo Kinji Ohno António Amorim Maria Luiza Saraiva-Pereira Laura Bannach Jardim Tohru Matsuura Jorge Sequeiros Isabel Silveira |
| author_sort | Teresa Almeida |
| collection | DOAJ |
| description | Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil. |
| first_indexed | 2024-12-12T22:05:34Z |
| format | Article |
| id | doaj.art-1a082cabc46244878381fb59c18483f0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T22:05:34Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a082cabc46244878381fb59c18483f02022-12-22T00:10:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0142e455310.1371/journal.pone.0004553Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10).Teresa AlmeidaIsabel AlonsoSandra MartinsEliana Marisa RamosLuísa AzevedoKinji OhnoAntónio AmorimMaria Luiza Saraiva-PereiraLaura Bannach JardimTohru MatsuuraJorge SequeirosIsabel SilveiraSpinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil.http://europepmc.org/articles/PMC2639644?pdf=render |
| spellingShingle | Teresa Almeida Isabel Alonso Sandra Martins Eliana Marisa Ramos Luísa Azevedo Kinji Ohno António Amorim Maria Luiza Saraiva-Pereira Laura Bannach Jardim Tohru Matsuura Jorge Sequeiros Isabel Silveira Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). PLoS ONE |
| title | Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). |
| title_full | Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). |
| title_fullStr | Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). |
| title_full_unstemmed | Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). |
| title_short | Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). |
| title_sort | ancestral origin of the attct repeat expansion in spinocerebellar ataxia type 10 sca10 |
| url | http://europepmc.org/articles/PMC2639644?pdf=render |
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