Fetal de novo mutations and preterm birth.
Preterm birth (PTB) affects ~12% of pregnancies in the US. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear. Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-04-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5384656?pdf=render |
| _version_ | 1818988537679183872 |
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| author | Jingjing Li John Oehlert Michael Snyder David K Stevenson Gary M Shaw |
| author_facet | Jingjing Li John Oehlert Michael Snyder David K Stevenson Gary M Shaw |
| author_sort | Jingjing Li |
| collection | DOAJ |
| description | Preterm birth (PTB) affects ~12% of pregnancies in the US. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear. Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associated with PTB. By analyzing whole-genome sequencing data from 816 trio families, for the first time, we observed the role of fetal de novo mutations in PTB. We observed a significant increase in de novo mutation burden in PTB fetal genomes. Our genomic analyses further revealed that affected genes by PTB de novo mutations were dosage sensitive, intolerant to genomic deletions, and their mouse orthologs were likely developmentally essential. These genes were significantly involved in early fetal brain development, which was further supported by our analysis of copy number variants identified from an independent PTB cohort. Our study indicates a new mechanism in PTB occurrence independently contributed from fetal genomes, and thus opens a new avenue for future PTB research. |
| first_indexed | 2024-12-20T19:24:10Z |
| format | Article |
| id | doaj.art-9eaadc0648a845fcbb41988f8d02714e |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T19:24:10Z |
| publishDate | 2017-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-9eaadc0648a845fcbb41988f8d02714e2022-12-21T19:28:55ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-04-01134e100668910.1371/journal.pgen.1006689Fetal de novo mutations and preterm birth.Jingjing LiJohn OehlertMichael SnyderDavid K StevensonGary M ShawPreterm birth (PTB) affects ~12% of pregnancies in the US. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear. Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associated with PTB. By analyzing whole-genome sequencing data from 816 trio families, for the first time, we observed the role of fetal de novo mutations in PTB. We observed a significant increase in de novo mutation burden in PTB fetal genomes. Our genomic analyses further revealed that affected genes by PTB de novo mutations were dosage sensitive, intolerant to genomic deletions, and their mouse orthologs were likely developmentally essential. These genes were significantly involved in early fetal brain development, which was further supported by our analysis of copy number variants identified from an independent PTB cohort. Our study indicates a new mechanism in PTB occurrence independently contributed from fetal genomes, and thus opens a new avenue for future PTB research.http://europepmc.org/articles/PMC5384656?pdf=render |
| spellingShingle | Jingjing Li John Oehlert Michael Snyder David K Stevenson Gary M Shaw Fetal de novo mutations and preterm birth. PLoS Genetics |
| title | Fetal de novo mutations and preterm birth. |
| title_full | Fetal de novo mutations and preterm birth. |
| title_fullStr | Fetal de novo mutations and preterm birth. |
| title_full_unstemmed | Fetal de novo mutations and preterm birth. |
| title_short | Fetal de novo mutations and preterm birth. |
| title_sort | fetal de novo mutations and preterm birth |
| url | http://europepmc.org/articles/PMC5384656?pdf=render |
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