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Purifying selection against pathogenic mitochondrial DNA in human T cells

Item Type:Article
Title:Purifying selection against pathogenic mitochondrial DNA in human T cells
Creators Name:Walker, M.A. and Lareau, C.A. and Ludwig, L.S. and Karaa, A. and Sankaran, V.G. and 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
Publisher:Massachusetts Medical Society
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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