Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorVILLELA, Darine
dc.contributor.authorSUEMOTO, Claudia K.
dc.contributor.authorLEITE, Renata
dc.contributor.authorPASQUALUCCI, Carlos Augusto
dc.contributor.authorGRINBERG, Lea T.
dc.contributor.authorPEARSON, Peter
dc.contributor.authorROSENBERG, Carla
dc.date.accessioned2018-09-13T15:22:33Z
dc.date.available2018-09-13T15:22:33Z
dc.date.issued2018
dc.description.abstractAging 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP [2013/08028-1, 2014/17132-0]
dc.identifier.citationNEURAL PLASTICITY, article ID 2406170, 9p, 2018
dc.identifier.doi10.1155/2018/2406170
dc.identifier.eissn1687-5443
dc.identifier.issn2090-5904
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/28008
dc.language.isoeng
dc.publisherHINDAWI LTD
dc.relation.ispartofNeural Plasticity
dc.rightsopenAccess
dc.rights.holderCopyright HINDAWI LTD
dc.subject.otherhuman neurons
dc.subject.othersomatic mutation
dc.subject.otheraging brain
dc.subject.otheraneuploidy
dc.subject.otherdisease
dc.subject.otherretrotransposition
dc.subject.wosNeurosciences
dc.titleIncreased DNA Copy Number Variation Mosaicism in Elderly Human Brain
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalVILLELA, Darine:Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cells Res Ctr, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP, Brazil
hcfmusp.author.externalPEARSON, Peter:Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cells Res Ctr, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP, Brazil
hcfmusp.author.externalROSENBERG, Carla:Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cells Res Ctr, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP, Brazil
hcfmusp.citation.scopus7
hcfmusp.contributor.author-fmusphcCLAUDIA KIMIE SUEMOTO
hcfmusp.contributor.author-fmusphcRENATA ELAINE PARAIZO LEITE
hcfmusp.contributor.author-fmusphcCARLOS AUGUSTO GONCALVES PASQUALUCCI
hcfmusp.contributor.author-fmusphcLEA TENENHOLZ GRINBERG
hcfmusp.description.articlenumber2406170
hcfmusp.origemWOS
hcfmusp.origem.pubmed30050570
hcfmusp.origem.scopus2-s2.0-85055009832
hcfmusp.origem.wosWOS:000438022900001
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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