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Mitochondrial diseases are potentially severe, incurable diseases resulting from dysfunctional mitochondria. Several important mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA), the genetic material contained within mitochondria, which is maternally inherited. Classical and modern therapeutic approaches exist to address the inheritance of mtDNA disease, but are potentially complicated by the fact that cellular mtDNA populations evolve according to poorly-understood dynamics during development and organismal lifetimes. We review these therapeutic approaches and models of mtDNA dynamics during development, and discuss the implications of recent results from these models for modern mtDNA therapies. We particularly highlight mtDNA segregation-differences in proliferative rates between different mtDNA haplotypes-as a potential and underexplored issue in such therapies. However, straightforward strategies exist to combat this and other potential therapeutic problems. In particular, we describe haplotype matching as an approach with the power to potentially ameliorate any expected issues from mtDNA incompatibility.

Original publication

DOI

10.1093/molehr/gau090

Type

Journal article

Journal

Mol Hum Reprod

Publication Date

01/2015

Volume

21

Pages

11 - 22

Keywords

development, haplotype matching, mitochondrial DNA, mtDNA segregation, preventing mtDNA disease, Biological Evolution, DNA, Mitochondrial, Databases, Genetic, Haplotypes, Humans, Mitochondria, Mitochondrial Diseases, Reproduction