Purifying selection against pathogenic mitochondrial DNA in human T cells

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Item Type:	Article
Title:	Purifying selection against pathogenic mitochondrial DNA in human T cells
Creators Name:	Walker, M.A., Lareau, C.A., Ludwig, L.S., Karaa, A., Sankaran, V.G., Regev, A. and Mootha, V.K.
Abstract:	Many mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). Patients' cells contain a mixture of mutant and nonmutant mtDNA (a phenomenon called heteroplasmy). The proportion of mutant mtDNA varies across patients and among tissues within a patient. We simultaneously assayed single-cell heteroplasmy and cell state in thousands of blood cells obtained from three unrelated patients who had A3243G-associated mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. We observed a broad range of heteroplasmy across all cell types but also found markedly reduced heteroplasmy in T cells, a finding consistent with purifying selection within this lineage. We observed this pattern in six additional patients who had heteroplasmic A3243G without strokelike episodes.
Keywords:	Genetic Polymorphism, MELAS Syndrome, Mitochondrial DNA, Mitochondrial Genome, Mononuclear Leukocytes, Mutation, T-Lymphocytes
Source:	New England Journal of Medicine
ISSN:	0028-4793
Publisher:	Massachusetts Medical Society
Volume:	383
Number:	16
Page Range:	1556-1563
Date:	15 October 2020
Official Publication:	https://doi.org/10.1056/NEJMoa2001265
PubMed:	View item in PubMed

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