Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development.
Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is sti...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-09-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010404 |
| _version_ | 1797989644156010496 |
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| author | Ja Hye Kim Shinwon Hwang Hyeonju Son Dongsun Kim Il Bin Kim Myeong-Heui Kim Nam Suk Sim Dong Seok Kim Yoo-Jin Ha Junehawk Lee Hoon-Chul Kang Jeong Ho Lee Sangwoo Kim |
| author_facet | Ja Hye Kim Shinwon Hwang Hyeonju Son Dongsun Kim Il Bin Kim Myeong-Heui Kim Nam Suk Sim Dong Seok Kim Yoo-Jin Ha Junehawk Lee Hoon-Chul Kang Jeong Ho Lee Sangwoo Kim |
| author_sort | Ja Hye Kim |
| collection | DOAJ |
| description | Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions. |
| first_indexed | 2024-04-11T08:23:34Z |
| format | Article |
| id | doaj.art-8adbe6b857864a21b9f02a86744335c8 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-11T08:23:34Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-8adbe6b857864a21b9f02a86744335c82022-12-22T04:34:51ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-09-01189e101040410.1371/journal.pgen.1010404Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development.Ja Hye KimShinwon HwangHyeonju SonDongsun KimIl Bin KimMyeong-Heui KimNam Suk SimDong Seok KimYoo-Jin HaJunehawk LeeHoon-Chul KangJeong Ho LeeSangwoo KimMost somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.https://doi.org/10.1371/journal.pgen.1010404 |
| spellingShingle | Ja Hye Kim Shinwon Hwang Hyeonju Son Dongsun Kim Il Bin Kim Myeong-Heui Kim Nam Suk Sim Dong Seok Kim Yoo-Jin Ha Junehawk Lee Hoon-Chul Kang Jeong Ho Lee Sangwoo Kim Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. PLoS Genetics |
| title | Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. |
| title_full | Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. |
| title_fullStr | Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. |
| title_full_unstemmed | Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. |
| title_short | Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. |
| title_sort | analysis of low level somatic mosaicism reveals stage and tissue specific mutational features in human development |
| url | https://doi.org/10.1371/journal.pgen.1010404 |
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