Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus 10398A>G.

ABSTRACT: Mitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer's disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT heteroplasmy was present throughout the entire MT genome for blood samples, we detected MT heteroplasmy only within the MT control region for brain samples. We observed that an MT variant 10398A>G (rs2853826) was significantly associated with overall MT heteroplasmy in brain tissue while also being linked with the largest number of distinct disease phenotypes of all ann

SUBMITTER: Smullen M 

PROVIDER: S-EPMC10300032 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature