Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm
Abstract
Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.
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STR instability is known to occur in the germline, but tissue-specific somatic variation in STR tract length has been reported.
“STR instability is known to occur in the germline, but tissue-specific somatic variation in STR tract length has been reported (Leeflang et al., 1995; Telenius et al., 1994; Wohrle et al., 1993; Wong et al., 1995; Zhang et al., 1994).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Telenius et al., 1994
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BackgroundDisease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries
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“STR instability is known to occur in the germline, but tissuespecific somatic variation in STR tract length has been reported (Leeflang et al., 1995; Telenius et al., 1994; Wöhrle et al., 1993; Wong et al., 1995; Zhang et al., 1994).”
BackgroundDynamic alternative DNA structures in biology and disease
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- Authors
- Telenius, H., Kremer, B., Goldberg, Y. P., Theilmann, J., Andrew, S. E., Zeisler, J., Adam, S., Greenberg, C., Ives, E. J., Clarke, L. A., & Hayden, M. R.
- Affiliations
- University of British Columbia (CA)
- Health Sciences Centre (CA)
- Memorial University of Newfoundland (CA)
- Venue
- Nature Genetics
- Published
- 1994-04-01
- Volume
- 6
- Issue
- 4
- Pages
- 409-414
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1986594553
- Cited by
- 439
- References
- 33
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 29 · 2023: 20 · 2022: 15 · 2021: 24 · 2020: 15 · 2019: 13 · 2018: 14 · 2017: 7 · 2016: 11 · 2015: 12 · 2014: 4 · 2013: 16 · 2012: 9
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Update notices
- correction (1994-05-01)
- Open access
- closed
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Huntington's disease, CAG repeat expansion, somatic mosaicism, gonadal mosaicism, spermatozoa, brain, cerebellum, basal ganglia, cerebral cortex, trinucleotide repeat instability
- MeSH terms
- Adult, Basal Ganglia, Blood Cells, Brain Chemistry, Child, Child, Preschool, DNA, Female, Humans, Huntington Disease, Male, Middle Aged, Mosaicism, Muscle Proteins, Muscles, Nerve Tissue Proteins, Organ Specificity, Repetitive Sequences, Nucleic Acid, Spermatozoa, Viscera, Polymerase Chain Reaction, Age of Onset
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