title: Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10).
abstract: 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.
authors.affiliation: UnIGENe, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Almeida
authors.forename: Isabel
authors.initials: I
authors.lastname: Alonso
authors.forename: Sandra
authors.initials: S
authors.lastname: Martins
authors.forename: Eliana Marisa
authors.initials: EM
authors.lastname: Ramos
authors.forename: Luísa
authors.initials: L
authors.lastname: Azevedo
authors.forename: Kinji
authors.initials: K
authors.lastname: Ohno
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Isabel
authors.initials: I
authors.lastname: Silveira
mesh_terms: D000067736:Ataxin-10; D001938:Brazil; D042622:DNA Repeat Expansion; D005190:Family; D018703:Founder Effect; D005828:Genetics, Population; D005843:Geography; D006801:Humans; D008800:Mexico; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011157:Population Dynamics
chemical_list: C503889:ATXN10 protein, human; D000067736:Ataxin-10; D009419:Nerve Tissue Proteins