Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells
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 tissue...
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| Format: | Article |
| Language: | English |
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Massachusetts Medical Society
2021
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| Online Access: | https://hdl.handle.net/1721.1/135482 |
| _version_ | 1826213746456920064 |
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| author | Walker, Melissa A Lareau, Caleb A Ludwig, Leif S Karaa, Amel Sankaran, Vijay G Regev, Aviv Mootha, Vamsi K |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Walker, Melissa A Lareau, Caleb A Ludwig, Leif S Karaa, Amel Sankaran, Vijay G Regev, Aviv Mootha, Vamsi K |
| author_sort | Walker, Melissa A |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:54:09Z |
| format | Article |
| id | mit-1721.1/135482 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:54:09Z |
| publishDate | 2021 |
| publisher | Massachusetts Medical Society |
| record_format | dspace |
| spelling | mit-1721.1/1354822023-02-22T20:02:44Z Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells Walker, Melissa A Lareau, Caleb A Ludwig, Leif S Karaa, Amel Sankaran, Vijay G Regev, Aviv Mootha, Vamsi K Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. 2021-10-27T20:23:39Z 2021-10-27T20:23:39Z 2020 2021-07-22T16:20:59Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135482 en 10.1056/NEJMOA2001265 New England Journal of Medicine 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. application/pdf Massachusetts Medical Society The New England Journal of Medicine |
| spellingShingle | Walker, Melissa A Lareau, Caleb A Ludwig, Leif S Karaa, Amel Sankaran, Vijay G Regev, Aviv Mootha, Vamsi K Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title | Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title_full | Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title_fullStr | Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title_full_unstemmed | Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title_short | Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells |
| title_sort | purifying selection against pathogenic mitochondrial dna in human t cells |
| url | https://hdl.handle.net/1721.1/135482 |
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