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...

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Bibliographic Details
Published in:PLoS genetics 2017-04, Vol.13 (4), p.e1006689-e1006689
Main Authors: Li, Jingjing, Oehlert, John, Snyder, Michael, Stevenson, David K, Shaw, Gary M
Format: Article
Language:English
Subjects:
Age
Animals
Autism
Behavior disorders
Biology and Life Sciences
Birth
Brain - growth & development
Brain - metabolism
Brain - pathology
Brain research
Copy number
Data processing
DNA Copy Number Variations - genetics
Drug dosages
Etiology
Families & family life
Female
Fetal Development - genetics
Fetus - pathology
Fetuses
Frameshift Mutation - genetics
Gene mutation
Genes
Genetic aspects
Genetic disorders
Genetic factors
Genetics
Genome, Human
Genomes
Genomic analysis
Genomics
Humans
Hypotheses
Inflammation
Medicine and Health Sciences
Mice
Morbidity
Mortality
Multiple births
Mutation
Pediatrics
People and Places
Physiological aspects
Precision medicine
Pregnancy
Premature birth
Premature Birth - genetics
Premature Birth - pathology
Research and Analysis Methods
Risk Factors
Sequence Deletion - genetics
Studies
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Description
Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006689