Contribution of retrotransposition to developmental disorders.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 10 2019
11 10 2019
Historique:
received:
28
11
2018
accepted:
11
09
2019
entrez:
13
10
2019
pubmed:
13
10
2019
medline:
6
2
2020
Statut:
epublish
Résumé
Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient's symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.
Identifiants
pubmed: 31604926
doi: 10.1038/s41467-019-12520-y
pii: 10.1038/s41467-019-12520-y
pmc: PMC6789007
doi:
Substances chimiques
Retroelements
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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