Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability
Short tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are character...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/515 |
| _version_ | 1797622113501184000 |
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| author | Stephanie Calluori Rebecca Stark Brandon L. Pearson |
| author_facet | Stephanie Calluori Rebecca Stark Brandon L. Pearson |
| author_sort | Stephanie Calluori |
| collection | DOAJ |
| description | Short tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are characterized by repeat instability. Longer repeat tracts are typically associated with earlier age of onset and increased disease severity. Environmental exposures are suspected to play a role in the pathogenesis of repeat expansion diseases. Here, we review the current knowledge of mechanisms of environmentally induced repeat instability in repeat expansion diseases. The current evidence demonstrates that environmental factors modulate repeat instability via DNA damage and induction of DNA repair pathways, with distinct mechanisms for repeat expansion and contraction. Of particular note, oxidative stress is a key mediator of environmentally induced repeat instability. The preliminary evidence suggests epigenetic modifications as potential mediators of environmentally induced repeat instability. Future research incorporating an array of environmental exposures, new human cohorts, and improved model systems, with a continued focus on cell-types, tissues, and critical windows, will aid in identifying mechanisms of environmentally induced repeat instability. Identifying environmental modulators of repeat instability and their mechanisms of action will inform preventions, therapies, and public health measures. |
| first_indexed | 2024-03-11T09:06:42Z |
| format | Article |
| id | doaj.art-23b617600bbd47cd925283fe12178fa6 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-11T09:06:42Z |
| publishDate | 2023-02-01 |
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| series | Biomedicines |
| spelling | doaj.art-23b617600bbd47cd925283fe12178fa62023-11-16T19:19:20ZengMDPI AGBiomedicines2227-90592023-02-0111251510.3390/biomedicines11020515Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat InstabilityStephanie Calluori0Rebecca Stark1Brandon L. Pearson2Department of Environmental Health Sciences, Mailman School of Public Health Columbia University, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health Columbia University, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health Columbia University, New York, NY 10032, USAShort tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are characterized by repeat instability. Longer repeat tracts are typically associated with earlier age of onset and increased disease severity. Environmental exposures are suspected to play a role in the pathogenesis of repeat expansion diseases. Here, we review the current knowledge of mechanisms of environmentally induced repeat instability in repeat expansion diseases. The current evidence demonstrates that environmental factors modulate repeat instability via DNA damage and induction of DNA repair pathways, with distinct mechanisms for repeat expansion and contraction. Of particular note, oxidative stress is a key mediator of environmentally induced repeat instability. The preliminary evidence suggests epigenetic modifications as potential mediators of environmentally induced repeat instability. Future research incorporating an array of environmental exposures, new human cohorts, and improved model systems, with a continued focus on cell-types, tissues, and critical windows, will aid in identifying mechanisms of environmentally induced repeat instability. Identifying environmental modulators of repeat instability and their mechanisms of action will inform preventions, therapies, and public health measures.https://www.mdpi.com/2227-9059/11/2/515repeat instabilityshort tandem repeatrepeat expansion diseasegene–environment interactionsenvironmentoxidative stress |
| spellingShingle | Stephanie Calluori Rebecca Stark Brandon L. Pearson Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability Biomedicines repeat instability short tandem repeat repeat expansion disease gene–environment interactions environment oxidative stress |
| title | Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability |
| title_full | Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability |
| title_fullStr | Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability |
| title_full_unstemmed | Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability |
| title_short | Gene–Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability |
| title_sort | gene environment interactions in repeat expansion diseases mechanisms of environmentally induced repeat instability |
| topic | repeat instability short tandem repeat repeat expansion disease gene–environment interactions environment oxidative stress |
| url | https://www.mdpi.com/2227-9059/11/2/515 |
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