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

• Grant number: 15/03148-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 30, 2015
• End date: July 29, 2015
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Nadja Cristhina de Souza Pinto
• Grantee: Daniela Tathiana Soltys
• Supervisor: Jason H. Bielas
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: 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)