Novel Intermediate ATXN10 Alleles in the Healthy Peruvian Population: A Matter of Indigenous American Ethnic Origin.
| Title: | Novel Intermediate ATXN10 Alleles in the Healthy Peruvian Population: A Matter of Indigenous American Ethnic Origin. |
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| Authors: | Milla-Neyra K; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru. k.milla.neurogenetica@gmail.com.; Araujo-Aliaga I; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.; Manrique-Enciso C; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Sarapura-Castro E; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.; Illanes-Manrique M; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.; Veliz-Otani D; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, MD, USA.; Saldarriaga-Mayo A; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.; Medina-Colque A; Dirección Regional de Salud de Puno, Puno, Peru.; Rios-Pinto J; Universidad Peruana Los Andes, Huancayo, Peru.; Cornejo-Herrera I; Universidad Privada de Tacna, Tacna, Peru.; Rivera-Valdivia A; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.; F Mata I; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Loesch D; Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, MD, USA.; Lozano-Vasquez L; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Universidad Peruana de Ciencias Aplicadas, Lima, Peru.; Bordia T; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; O'Connor T; Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, MD, USA.; Schüle B; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Cornejo-Olivas M; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru. mcornejool@cientifica.edu.pe.; Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru. mcornejool@cientifica.edu.pe. |
| Source: | Cerebellum (London, England) [Cerebellum] 2025 Feb 07; Vol. 24 (2), pp. 44. Date of Electronic Publication: 2025 Feb 07. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: United States NLM ID: 101089443 Publication Model: Electronic Cited Medium: Internet ISSN: 1473-4230 (Electronic) Linking ISSN: 14734222 NLM ISO Abbreviation: Cerebellum Subsets: MEDLINE |
| Imprint Name(s): | Publication: : New York : Springer; Original Publication: London : Martin Dunitz, c2002- |
| MeSH Terms: | Ataxin-10*/genetics ; Spinocerebellar Ataxias*/genetics ; Spinocerebellar Ataxias*/ethnology ; Indians, South American*/genetics; Peru/ethnology ; Ethnicity/genetics ; Humans ; Alleles ; Male ; Female ; Gene Frequency ; Adult ; DNA Repeat Expansion |
| Abstract: | Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease predominant in Latin American individuals with Indigenous American ancestry. SCA10 is caused by an expansion of ATTCT repeat within the ATXN10 gene. Healthy individuals carry 9-32 ATTCT repeats, whereas SCA10 patients carry an expansion of 280 repeats and higher. Recently, intermediate alleles (over than 32 repeats) have been identified in healthy Peruvian Indigenous American individuals, with unclear significance. This study aims to characterize the variability of the ATTCT repeats within the ATXN10 gene across self-declared Indigenous American and Mestizo subpopulations from Peru. A total of 871 samples (754 Mestizo and 117 Indigenous American) were analyzed using PCR, and RP-PCR when suspecting apparent homozygosity due to larger alleles. 8.7% of the total of healthy individuals (76/871) carry at least one intermediate allele. The 14-repeat allele being the most common for both subpopulations (41.5%). Intermediate alleles were detected in the Peruvian population (4.5%) with a significantly higher frequency among self-declared Indigenous American compared to Mestizo, suggesting a possible association with the ethnic origin. The G allele at the SNP rs41524547 had a frequency of 51.39% in individuals with intermediate alleles, with not significantly difference between subpopulations. Further analysis should be performed to confirm the size and composition of ATTCT repeat tract, as well as the contribution of rs41524547 in SCA10.; (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethical Approval: The study was approved by the Ethics Committee at INCN, called the ‘Comité Institucional de Ética en Investigación del Instituto Nacional de Ciencias Neurológicas,’ IRB number 016-2021-CIEI-INCN. This research was conducted in accordance with the Declaration of Helsinki. The sample donors provided written informed consent for use of their genetic and clinical data for anonymized ongoing and future research studies. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Competing Interests: The authors declare no competing interests. |
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| Grant Information: | Convention N°067-2020-01 (Contract N° 148-2020-FONDECYT) Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica (CONCYTEC-PROCIENCIA) |
| Contributed Indexing: | Keywords: ATXN10; Allelic distribution; Indigenous American; RP-PCR; SCA10 |
| Substance Nomenclature: | 0 (Ataxin-10); 0 (ATXN10 protein, human) |
| SCR Disease Name: | Spinocerebellar Ataxia 10 |
| Entry Date(s): | Date Created: 20250207 Date Completed: 20250506 Latest Revision: 20250513 |
| Update Code: | 20260130 |
| DOI: | 10.1007/s12311-025-01795-1 |
| PMID: | 39918768 |
| Database: | MEDLINE |
Journal Article