Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells.
Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells.
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DOI：
10.1056/nejmoa2001265
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发表时间：
2020-10-15
期刊：
影响因子：
--
通讯作者：
Mootha VK
中科院分区：
文献类型：
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作者：
Walker MA;Lareau CA;Ludwig LS;Karaa A;Sankaran VG;Regev A;Mootha VK
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. (Funded by the Marriott Foundation and others.)
