{"doi":"10.1093/hmg/ddae092","title":"Extended haplotype with rs41524547-G defines the ancestral origin of SCA10","abstract":"Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5'-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia-a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.","journal":"Human Molecular Genetics","year":2024,"id":446892,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9386,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":381849,"name":"Anjana Tiwari","orcid":null,"position":1,"is_corresponding":false},{"id":380172,"name":"Vera I. Hashem","orcid":"0000-0002-5471-8769","position":2,"is_corresponding":false},{"id":1264100,"name":"Linwei Zhang","orcid":"0000-0002-7094-8345","position":3,"is_corresponding":false},{"id":1264531,"name":"Desmond Zeng","orcid":null,"position":4,"is_corresponding":false},{"id":1264532,"name":"Justin Vincent","orcid":null,"position":5,"is_corresponding":false},{"id":1252980,"name":"Maria Jose Arredondo","orcid":null,"position":6,"is_corresponding":false},{"id":1264533,"name":"Kristy L Johnson","orcid":null,"position":7,"is_corresponding":false},{"id":1264534,"name":"Shi Rui Gan","orcid":null,"position":8,"is_corresponding":false},{"id":1264101,"name":"Ichiro Yabe","orcid":"0000-0002-1734-7997","position":9,"is_corresponding":false},{"id":1209499,"name":"Laurits Skov","orcid":"0000-0001-9582-0391","position":10,"is_corresponding":false},{"id":380176,"name":"Astrid Rasmussen","orcid":"0000-0001-7744-2948","position":11,"is_corresponding":false},{"id":380178,"name":"Tetsuo Ashizawa","orcid":"0000-0001-7180-2869","position":12,"is_corresponding":false},{"id":380177,"name":"Karen N. McFarland","orcid":"0000-0002-9952-8678","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:01:54.980444Z","pmid":"38832639","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}