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Quantification and identification of mitochondrial DNA mutations in brains from individuals with Alzheimer's Disease

Grant number: 15/03148-4
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): April 30, 2015
Effective date (End): July 29, 2015
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal researcher:Nadja Cristhina de Souza Pinto
Grantee:Daniela Tathiana Soltys
Supervisor abroad: Jason H. Bielas
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Fred Hutchinson Cancer Research Center (Fred Hutch), United States  
Associated to the scholarship:12/11889-6 - Status of DNA base excision repair in brain from individuals with Alzheimer's Disease, BP.PD

Abstract

Mitochondrial dysfunction appears as an early event in Alzheimer's disease (AD) pathology and in other neurodegenerative diseases. AD individuals accumulate oxidized DNA lesions in the mitochondrial genome (mtDNA) when compared to age-matched control individuals, which is believed to play a causal role in the mitochondrial dysfunction observed in the AD pathology. However, it is not clear whether these lesions lead to a higher mutational load in the mtDNA. To get a better understanding of the mutation rate and spectrum in the mitochondrial genome from AD brains, we propose to analyze the mtDNA from brains from control groups, AD and asymptomatic AD individuals, using the Random Mutation Capture Assay, a single-molecule sequencing approach that allows the detection of even rare and low frequency mutations. (AU)

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