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 th...
Published in: | Human Molecular Genetics |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Oxford University Press (OUP)
2024
|
Subjects: | |
Online Access: | http://dx.doi.org/10.1093/hmg/ddae092 https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddae092/58082590/ddae092.pdf |
id |
croxfordunivpr:10.1093/hmg/ddae092 |
---|---|
record_format |
openpolar |
spelling |
croxfordunivpr:10.1093/hmg/ddae092 2024-06-23T07:51:43+00:00 Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 McFarland, Karen N Tiwari, Anjana Hashem, Vera Zhang, Linwei Zeng, Desmond Vincent, Justin Arredondo, Maria J Johnson, Kristy L Gan, Shi Rui Yabe, Ichiro Skov, Laurits Rasmussen, Astrid Ashizawa, Tetsuo 2024 http://dx.doi.org/10.1093/hmg/ddae092 https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddae092/58082590/ddae092.pdf en eng Oxford University Press (OUP) https://academic.oup.com/pages/standard-publication-reuse-rights Human Molecular Genetics ISSN 0964-6906 1460-2083 journal-article 2024 croxfordunivpr https://doi.org/10.1093/hmg/ddae092 2024-06-11T04:19:03Z 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. Article in Journal/Newspaper Bering Land Bridge Oxford University Press Human Molecular Genetics |
institution |
Open Polar |
collection |
Oxford University Press |
op_collection_id |
croxfordunivpr |
language |
English |
description |
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. |
format |
Article in Journal/Newspaper |
author |
McFarland, Karen N Tiwari, Anjana Hashem, Vera Zhang, Linwei Zeng, Desmond Vincent, Justin Arredondo, Maria J Johnson, Kristy L Gan, Shi Rui Yabe, Ichiro Skov, Laurits Rasmussen, Astrid Ashizawa, Tetsuo |
spellingShingle |
McFarland, Karen N Tiwari, Anjana Hashem, Vera Zhang, Linwei Zeng, Desmond Vincent, Justin Arredondo, Maria J Johnson, Kristy L Gan, Shi Rui Yabe, Ichiro Skov, Laurits Rasmussen, Astrid Ashizawa, Tetsuo Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
author_facet |
McFarland, Karen N Tiwari, Anjana Hashem, Vera Zhang, Linwei Zeng, Desmond Vincent, Justin Arredondo, Maria J Johnson, Kristy L Gan, Shi Rui Yabe, Ichiro Skov, Laurits Rasmussen, Astrid Ashizawa, Tetsuo |
author_sort |
McFarland, Karen N |
title |
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
title_short |
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
title_full |
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
title_fullStr |
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
title_full_unstemmed |
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10 |
title_sort |
extended haplotype with rs41524547-g defines the ancestral origin of sca10 |
publisher |
Oxford University Press (OUP) |
publishDate |
2024 |
url |
http://dx.doi.org/10.1093/hmg/ddae092 https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddae092/58082590/ddae092.pdf |
genre |
Bering Land Bridge |
genre_facet |
Bering Land Bridge |
op_source |
Human Molecular Genetics ISSN 0964-6906 1460-2083 |
op_rights |
https://academic.oup.com/pages/standard-publication-reuse-rights |
op_doi |
https://doi.org/10.1093/hmg/ddae092 |
container_title |
Human Molecular Genetics |
_version_ |
1802642839144759296 |