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Nat Commun. 2019 Jun 26;10(1):2792. doi: 10.1038/s41467-019-10642-x.

Common and distinct transcriptional signatures of mammalian embryonic lethality.

Author information

1
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, UK.
2
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge, CB2 0AW, UK.
3
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
4
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK.
5
Division of Anatomy, MIC, Medical University of Vienna, Waehringerstr. 13, 1090, Wien, Austria.
6
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
7
Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
8
Departments of Biochemistry & Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
9
Camena Bioscience, The Science Village, Chesterford Research Park, Cambridge, CB10 1XL, UK.
10
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
11
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
12
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, UK. emb81@cam.ac.uk.
13
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge, CB2 0AW, UK. emb81@cam.ac.uk.

Abstract

The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4-36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders.

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