Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain
Aging is a complex process strongly determined by genetics. Previous reports have shown that the genome of neuronal cells displays somatic genomic mosaicism including DNA copy number variations (CNVs). CNVs represent a significant source of genetic variation in the human genome and have been implica...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2018/2406170 |
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| author | Darine Villela Claudia K. Suemoto Renata Leite Carlos Augusto Pasqualucci Lea T. Grinberg Peter Pearson Carla Rosenberg |
| author_facet | Darine Villela Claudia K. Suemoto Renata Leite Carlos Augusto Pasqualucci Lea T. Grinberg Peter Pearson Carla Rosenberg |
| author_sort | Darine Villela |
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| description | Aging is a complex process strongly determined by genetics. Previous reports have shown that the genome of neuronal cells displays somatic genomic mosaicism including DNA copy number variations (CNVs). CNVs represent a significant source of genetic variation in the human genome and have been implicated in several disorders and complex traits, representing a potential mechanism that contributes to neuronal diversity and the etiology of several neurological diseases and provides new insights into the normal, complex functions of the brain. Nonetheless, the features of somatic CNV mosaicism in nondiseased elderly brains have not been investigated. In the present study, we demonstrate a highly significant increase in the number of CNVs in nondiseased elderly brains compared to the blood. In two neural tissues isolated from paired postmortem samples (same individuals), we found a significant increase in the frequency of deletions in both brain areas, namely, the frontal cortex and cerebellum. Also, deletions were found to be significantly larger when present only in the cerebellum. The sizes of the variants described here were in the 150–760 kb range, and importantly, nearly all of them were present in the Database of Genomic Variants (common variants). Nearly all evidence of genome structural variation in human brains comes from studies detecting changes in single cells which were interpreted as derived from independent, isolated mutational events. The observations based on array-CGH analysis indicate the existence of an extensive clonal mosaicism of CNVs within and between the human brains revealing a different type of variation that had not been previously characterized. |
| format | Article |
| id | doaj-art-c5b633419d2849e7ab8542c1294f6123 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-c5b633419d2849e7ab8542c1294f61232025-02-03T07:26:11ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/24061702406170Increased DNA Copy Number Variation Mosaicism in Elderly Human BrainDarine Villela0Claudia K. Suemoto1Renata Leite2Carlos Augusto Pasqualucci3Lea T. Grinberg4Peter Pearson5Carla Rosenberg6Human Genome and Stem Cells Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, BrazilDiscipline of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, BrazilBrazilian Aging Brain Study Group-LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, BrazilBrazilian Aging Brain Study Group-LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, BrazilBrazilian Aging Brain Study Group-LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, BrazilHuman Genome and Stem Cells Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, BrazilHuman Genome and Stem Cells Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, BrazilAging is a complex process strongly determined by genetics. Previous reports have shown that the genome of neuronal cells displays somatic genomic mosaicism including DNA copy number variations (CNVs). CNVs represent a significant source of genetic variation in the human genome and have been implicated in several disorders and complex traits, representing a potential mechanism that contributes to neuronal diversity and the etiology of several neurological diseases and provides new insights into the normal, complex functions of the brain. Nonetheless, the features of somatic CNV mosaicism in nondiseased elderly brains have not been investigated. In the present study, we demonstrate a highly significant increase in the number of CNVs in nondiseased elderly brains compared to the blood. In two neural tissues isolated from paired postmortem samples (same individuals), we found a significant increase in the frequency of deletions in both brain areas, namely, the frontal cortex and cerebellum. Also, deletions were found to be significantly larger when present only in the cerebellum. The sizes of the variants described here were in the 150–760 kb range, and importantly, nearly all of them were present in the Database of Genomic Variants (common variants). Nearly all evidence of genome structural variation in human brains comes from studies detecting changes in single cells which were interpreted as derived from independent, isolated mutational events. The observations based on array-CGH analysis indicate the existence of an extensive clonal mosaicism of CNVs within and between the human brains revealing a different type of variation that had not been previously characterized.http://dx.doi.org/10.1155/2018/2406170 |
| spellingShingle | Darine Villela Claudia K. Suemoto Renata Leite Carlos Augusto Pasqualucci Lea T. Grinberg Peter Pearson Carla Rosenberg Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain Neural Plasticity |
| title | Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain |
| title_full | Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain |
| title_fullStr | Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain |
| title_full_unstemmed | Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain |
| title_short | Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain |
| title_sort | increased dna copy number variation mosaicism in elderly human brain |
| url | http://dx.doi.org/10.1155/2018/2406170 |
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