ArticleHuman genetics2014
Modifiers of (CAG)(n) instability in Machado-Joseph disease (MJD/SCA3) transmissions: an association study with DNA replication, repair and recombination genes.
Article in Human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- Deep-embedded clustering by relevant scales and genome-wide association study in autism.PloS one · 2025Article
- CAG repeat mosaicism is gene specific in spinocerebellar ataxias.American journal of human genetics · 2024Article
- Article
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Homozygous spinocerebellar ataxia type 3 in China: a case report.The Journal of international medical research · 2021Article
- Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington's Disease.Journal of Huntington's disease · 2021Review
- Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3.Cerebellum (London, England) · 2020Article
- Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.Science translational medicine · 2020Article
- Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease.Aging · 2020Article
- A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.Nature genetics · 2020Article
- Repeat Instability in the Fragile X-Related Disorders: Lessons from a Mouse Model.Brain sciences · 2019Article
- Spinocerebellar ataxia: an update.Journal of neurology · 2019Review
- Paradigm for disease deconvolution in rare neurodegenerative disorders in Indian population: insights from studies in cerebellar ataxias.Journal of genetics · 2018Article
- The central role of DNA damage and repair in CAG repeat diseases.Disease models & mechanisms · 2018Review
- A Defective mRNA Cleavage and Polyadenylation Complex Facilitates Expansions of Transcribed (GAA)Cell reports · 2017Article
- Contraction of fully expanded FMR1 alleles to the normal range: predisposing haplotype or rare events?Journal of human genetics · 2017Article
- Modulation of trinucleotide repeat instability by DNA polymerase β polymorphic variant R137Q.PloS one · 2017Article
- Review
- The Repeat Expansion Diseases: The dark side of DNA repair.DNA repair · 2015Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Twelve neurological disorders are caused by gene-specific CAG/CTG repeat expansions that are highly unstable upon transmission to offspring. This intergenerational repeat instability is clinically relevant since disease onset, progression and severity are associated with repeat size. Studies of model organisms revealed the involvement of some DNA replication and repair genes in the process of repeat instability, however, little is known about their role in patients. Here, we used an association study to search for genetic modifiers of (CAG)n instability in 137 parent-child transmissions in Machado-Joseph disease (MJD/SCA3). With the hypothesis that variants in genes involved in DNA replication, repair or recombination might alter the MJD CAG instability patterns, we screened 768 SNPs from 93 of these genes. We found a variant in ERCC6 (rs2228528) associated with an expansion bias of MJD alleles. When using a gene-gene interaction model, the allele combination G-A (rs4140804-rs2972388) of RPA3-CDK7 is also associated with MJD instability in a direction-dependent manner. Interestingly, the transcription-coupled repair factor ERCC6 (aka CSB), the single-strand binding protein RPA, and the CDK7 kinase part of the TFIIH transcription repair complex, have all been linked to transcription-coupled repair. This is the first study performed in patient samples to implicate specific modifiers of CAG instability in humans. In summary, we found variants in three transcription-coupled repair genes associated with the MJD mutation that points to distinct mechanisms of (CAG)n instability.
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