Contribution of retrotransposition to developmental disorders.
Nat Commun
; 10(1): 4630, 2019 10 11.
Article
em En
| MEDLINE
| ID: mdl-31604926
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Deficiências do Desenvolvimento
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Retroelementos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article