Aging and neurodegeneration are associated with increased mutations in single human neurons

Publication Date:
2018-02-03
Publisher:
American Association for the Advancement of Science (AAAS)
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
Keywords:
Neuroscience
Published by:
http://www.aaas.org/
_version_ 1836398776752799744
autor Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
beschreibung It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
citation_standardnr 6154426
datenlieferant ipn_articles
feed_id 25
feed_publisher American Association for the Advancement of Science (AAAS)
feed_publisher_url http://www.aaas.org/
insertion_date 2018-02-03
journaleissn 1095-9203
journalissn 0036-8075
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Association for the Advancement of Science (AAAS)
quelle Science
relation http://science.sciencemag.org/cgi/content/short/359/6375/555?rss=1
schlagwort Neuroscience
search_space articles
shingle_author_1 Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
shingle_author_2 Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
shingle_author_3 Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
shingle_author_4 Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
shingle_catch_all_1 Aging and neurodegeneration are associated with increased mutations in single human neurons
Neuroscience
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_2 Aging and neurodegeneration are associated with increased mutations in single human neurons
Neuroscience
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_3 Aging and neurodegeneration are associated with increased mutations in single human neurons
Neuroscience
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_4 Aging and neurodegeneration are associated with increased mutations in single human neurons
Neuroscience
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., Walsh, C. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_title_1 Aging and neurodegeneration are associated with increased mutations in single human neurons
shingle_title_2 Aging and neurodegeneration are associated with increased mutations in single human neurons
shingle_title_3 Aging and neurodegeneration are associated with increased mutations in single human neurons
shingle_title_4 Aging and neurodegeneration are associated with increased mutations in single human neurons
timestamp 2025-06-30T23:32:27.978Z
titel Aging and neurodegeneration are associated with increased mutations in single human neurons
titel_suche Aging and neurodegeneration are associated with increased mutations in single human neurons
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uid ipn_articles_6154426