Genetic Determinants Influencing the Maternal Transmission and Somatic Accumulation of Mitochondrial Mutations
Abstract
We are using the common fruit fly, Drosophila melanogaster, as a model organism to pursue two aims. The first aim is focused on using a novel, high accuracy, next-generation sequencing methodology to perform a genome wide screen for genes involved in selecting against the accumulation and/or transmission of mtDNA mutations. The second aim is focused on characterizing the effects of putative modifiers on mitochondrial bioenergetics and morphology in hopes of providing insight into how these modifiers function. During the current reporting period, we have determined that the exonuclease deficient Pol-gamma strains that we originally proposed to use for our screening studies are likely not suitable due to the fact that mutations accumulate in the eggs during oogenesis. To solve this problem, we have developed a mitochondrially targeted cytidine deaminase, APOBEC1, expressing fly strains that express this protein solely in the germline or solely in the somatic tissue. We have begun to characterize the flies expressing APOBEC1 in the somatic tissue. This strain shows a large increase in Cright arrowT/Gright arrowA mutations, as expected, as well as a significantly reduced lifespan and loss of climbing ability. We are beginning the characterization of the germline expressing strain. We will begin our screening efforts upon the completion of our characterizations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1063027
Entities
People
- Monica Sanchez-Contreras
- Scott R. Kennedy
Organizations
- University of Washington