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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain

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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]
Total Authors: 7
[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
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 5

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)

FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/17132-0 - Use of Next Generation Sequencing to study karyotypes with different number of X chromosome
Grantee:Darine Christina Maia Villela
Support type: Scholarships in Brazil - Post-Doctorate