Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells
Name
nejmoa2001265.pdf
Description
Published version
Size
766.46 KB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Walker, Melissa A
Lareau, Caleb A
Ludwig, Leif S
Karaa, Amel
Sankaran, Vijay G
Regev, Aviv
Mootha, Vamsi K
Date Issued
2020
Journal
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Version
Final published version
Abstract
Copyright © 2020 Massachusetts Medical Society. 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1056/NEJMOA2001265
