Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion
Abstract
We demonstrate here that somatic variation of CGG repeat length is based on a mosaic of cells with different but stable FMR-1 alleles and does not reflect permanent mitotic instability. The length of a particular allele in an individual cell was maintained in progeny cells establishing a clone. The mutation patterns of multiple repeats in the DNA of fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and expansion to full mutation are generated post-conceptionally by the same molecular mechanism in a particular window of early development.
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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 Wohrle et al., 1993
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On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability
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Disease-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).”
BackgroundCharacterization of the full fragile X syndrome mutation in fetal gametes
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Screening for fragile X syndrome.
Murray, Cuckle, Taylor, & Hewison (1997) · Health Technology Assessment · doi:10.3310/hta1040 · Cited by 60 · see citing works
- Authors
- Wöhrle, D., Hennig, I., Vogel, W., & Steinbach, P.
- Affiliations
- Universität Ulm (DE)
- Venue
- Nature Genetics
- Published
- 1993-06
- Volume
- 4
- Issue
- 2
- Pages
- 140-142
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2094895064
- Cited by
- 174
- References
- 23
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 15.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- fragile X syndrome, FMR1 gene, CGG trinucleotide repeat, repeat expansion, mitotic stability, somatic mosaicism, full mutation, cell clones, fetal tissue, early development, trinucleotide repeat instability
- MeSH terms
- Alleles, Cell Differentiation, Cell Division, Clone Cells, Female, Embryonic and Fetal Development, Fetus, Fibroblasts, Fragile X Syndrome, Gene Amplification, Humans, Male, Mitosis, Mosaicism, Nerve Tissue Proteins, Placenta, Repetitive Sequences, Nucleic Acid, RNA-Binding Proteins, Fragile X Messenger Ribonucleoprotein 1, Fragile X Mental Retardation Protein
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