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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain

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Autor(es):
Villela, Darine [1] ; Suemoto, Claudia K. [2, 3] ; Leite, Renata [2] ; Pasqualucci, Carlos Augusto [2, 4] ; Grinberg, Lea T. [2, 5] ; Pearson, Peter [1] ; Rosenberg, Carla [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cells Res Ctr, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Pathol, Med Sch, Brazilian Aging Brain Study Grp LIM22, Ave Doutor Arnaldo 455, BR-01246000 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Med Sch, Dept Internal Med, Discipline Geriatr, Ave Doutor Arnaldo 455, BR-01246000 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Med Sch, Dept Pathol, Ave Doutor Arnaldo 455, BR-01246000 Sao Paulo, SP - Brazil
[5] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 675 Nelson Rising Lane, POB 1207, San Francisco, CA 94143 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: NEURAL PLASTICITY; 2018.
Citações Web of Science: 1
Resumo

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. (AU)

Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
Beneficiário:Mayana Zatz
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 14/17132-0 - Uso de Next Generation Sequencing na avaliação de cariótipos com número variável de cópias do cromossomo X
Beneficiário:Darine Christina Maia Villela
Linha de fomento: Bolsas no Brasil - Pós-Doutorado