Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:377 |
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| Enthalten in: |
Science (New York, N.Y.) - 377(2022), 6605 vom: 29. Juli, Seite 511-517 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bae, Taejeong [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 01.08.2022 Date Revised 28.08.2023 published: Print-Electronic CommentIn: Med. 2022 Oct 14;3(10):648-650. - PMID 36242998 Citation Status MEDLINE |
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| doi: |
10.1126/science.abm6222 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM344209008 |
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| 245 | 1 | 0 | |a Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability |
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| 500 | |a CommentIn: Med. 2022 Oct 14;3(10):648-650. - PMID 36242998 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism | ||
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