TY - JOUR
T1 - Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation
AU - on behalf of Rede Neurogenetica
AU - Bampi, Giovana B.
AU - Bisso-Machado, Rafael
AU - Hünemeier, Tábita
AU - Gheno, Tailise C.
AU - Furtado, Gabriel V.
AU - Veliz-Otani, Diego
AU - Cornejo-Olivas, Mario
AU - Mazzeti, Pillar
AU - Bortolini, Maria Cátira
AU - Jardim, Laura B.
AU - Saraiva-Pereira, Maria Luiza
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - ATXN10
KW - Amerindians
KW - Ancestral origin
KW - Founder effect
KW - Haplotypes
KW - SCA10
UR - http://www.scopus.com/inward/record.url?scp=85029417115&partnerID=8YFLogxK
U2 - 10.1007/s12017-017-8464-8
DO - 10.1007/s12017-017-8464-8
M3 - Artículo
C2 - 28905220
AN - SCOPUS:85029417115
SN - 1535-1084
VL - 19
SP - 501
EP - 509
JO - NeuroMolecular Medicine
JF - NeuroMolecular Medicine
IS - 4
ER -