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Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models

Repeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of D...

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Autores principales: Zhao, Xiaonan, McHugh, Cassandra, Coffey, Sydney R., Jimenez, Diego Antonio, Adams, Elizabeth, Carroll, Jeffrey B., Usdin, Karen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118036/
https://www.ncbi.nlm.nih.gov/pubmed/35403689
http://dx.doi.org/10.1242/dmm.049453
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author Zhao, Xiaonan
McHugh, Cassandra
Coffey, Sydney R.
Jimenez, Diego Antonio
Adams, Elizabeth
Carroll, Jeffrey B.
Usdin, Karen
author_facet Zhao, Xiaonan
McHugh, Cassandra
Coffey, Sydney R.
Jimenez, Diego Antonio
Adams, Elizabeth
Carroll, Jeffrey B.
Usdin, Karen
author_sort Zhao, Xiaonan
collection PubMed
description Repeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the fragile X-related disorders, Huntington's disease, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 2. We found that DNA isolated from stool is a much better indicator of somatic expansion than DNA from blood. As stool is a sensitive and noninvasive source of DNA, it can be useful for studies of factors affecting the risk of expansion, or the monitoring of treatments aimed at reducing expansion in preclinical trials, as it would allow expansions to be examined longitudinally in the same animal and allow significant changes in expansion to be observed much earlier than is possible with other DNA sources.
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spelling pubmed-91180362022-05-19 Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models Zhao, Xiaonan McHugh, Cassandra Coffey, Sydney R. Jimenez, Diego Antonio Adams, Elizabeth Carroll, Jeffrey B. Usdin, Karen Dis Model Mech Resource Article Repeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the fragile X-related disorders, Huntington's disease, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 2. We found that DNA isolated from stool is a much better indicator of somatic expansion than DNA from blood. As stool is a sensitive and noninvasive source of DNA, it can be useful for studies of factors affecting the risk of expansion, or the monitoring of treatments aimed at reducing expansion in preclinical trials, as it would allow expansions to be examined longitudinally in the same animal and allow significant changes in expansion to be observed much earlier than is possible with other DNA sources. The Company of Biologists Ltd 2022-05-13 /pmc/articles/PMC9118036/ /pubmed/35403689 http://dx.doi.org/10.1242/dmm.049453 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Resource Article
Zhao, Xiaonan
McHugh, Cassandra
Coffey, Sydney R.
Jimenez, Diego Antonio
Adams, Elizabeth
Carroll, Jeffrey B.
Usdin, Karen
Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title_full Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title_fullStr Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title_full_unstemmed Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title_short Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
title_sort stool is a sensitive and noninvasive source of dna for monitoring expansion in repeat expansion disease mouse models
topic Resource Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118036/
https://www.ncbi.nlm.nih.gov/pubmed/35403689
http://dx.doi.org/10.1242/dmm.049453
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