Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Whole embryo RNA-seq of 73 mouse mutant lines and baseline controls from the Mouse Genetics Project (DMDD)

ABSTRACT: The Deciphering the Mechanisms of Developmental Disorders (DMDD) programme analyses the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines. Here we show that single whole embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) uncovers transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. Further, we separate embryonic delay signatures from line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during somitogenesis. Collectively, this work provides a rich resource to further our understanding of early embryonic developmental disorders.

INSTRUMENT(S): Illumina HiSeq 2500, Illumina HiSeq 2000

ORGANISM(S): Mus musculus

SUBMITTER: Elisabeth Busch-Nentwich

PROVIDER: E-MTAB-7322 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Common and distinct transcriptional signatures of mammalian embryonic lethality.

Collins John E JE White Richard J RJ Staudt Nicole N Sealy Ian M IM Packham Ian I Wali Neha N Tudor Catherine C Mazzeo Cecilia C Green Angela A Siragher Emma E Ryder Edward E White Jacqueline K JK Papatheodoru Irene I Tang Amy A Füllgrabe Anja A Billis Konstantinos K Geyer Stefan H SH Weninger Wolfgang J WJ Galli Antonella A Hemberger Myriam M Stemple Derek L DL Robertson Elizabeth E Smith James C JC Mohun Timothy T Adams David J DJ Busch-Nentwich Elisabeth M EM

Nature communications 20190626 1

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 ...[more]

PMID: 31243271

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Project description:The DMDD Programme (Deciphering the Mechanisms of Developmental Disorders) provides a free online database of morphological and molecular phenotypes from embryonic-lethal mouse gene knockouts (http://www.dmdd.org.uk/). Embryos are imaged using HREM, placentas are examined by histology and mutant embryo mRNA expression profiles are compared to wild type. Total RNA was extracted from somite number staged homozygous mutant, heterozygous and sibling wild-type E9.5 whole C57BL/6N embryos and DNase treated. The embryos were derived from Mouse Genetics Programme gene knockout lines defined as homozygous embryonic lethal (http://www.sanger.ac.uk/science/collaboration/mouse-resource-portal). Stranded RNA-seq libraries were constructed using the Illumina TruSeq Stranded RNA protocol with oligo dT pulldown. Notes about samples and libraries: (1) The knockout alleles in this project were: Cnot4: Cnot4^tm1b(EUCOMM)Wtsi ; Ssr2: Ssr2^tm1b(EUCOMM)Wtsi ; 4933434E20Rik: 4933434E20Rik^tm1a(EUCOMM)Wtsi ; 1700007K13Rik: 1700007K13Rik^tm2b(EUCOMM)Wtsi ; Camsap3: Camsap3^tm1a(EUCOMM)Wtsi ; Anks6: Anks6^tm1b(KOMP)Wtsi ; Pdzk1: Pdzk1^tm2b(EUCOMM)Wtsi ; Otud7b: Otud7b^tm1b(EUCOMM)Wtsi ; Adamts3: Adamts3^tm1b(KOMP)Wtsi; Mir96: Mir96^tm2.2WTSI ; Cyp11a1: Cyp11a1^tm1b(EUCOMM)Hmgu and Traf6: Traf6^tm2a(EUCOMM)Wtsi. (2) A combination of litter identifier and embryo identifier within a litter will unambiguously identify a single embryo used in this study. (3) There is a margin of error for the somite-stage information (+/- 1 somite) because some embryos could be in between somite stages. (4) There are a minimum of three biological replicates per line. (5) Sex of the embryos was determined post-RNA-seq by looking at the expression of Xist (strong expression in females only). (6) Libraries were constructed in batches comprising multiple litters from one line from RNA-extraction to sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ .

Project description:The DMDD Programme (Deciphering the Mechanisms of Developmental Disorders, https://dmdd.org.uk/) provides a free online database of morphological and molecular phenotypes from embryonic-lethal mouse gene knockouts (http://www.dmdd.org.uk/). Embryos are imaged using HREM, placentas are examined by histology and mutant embryo mRNA expression profiles are compared to wild type. To underpin these investigations we have produced a comprehensive time series of gene expression through normal embryo development. Total RNA was extracted from somite number staged, second generation genotypically wild type, C57BL/6N embryos of mixed G0 linages from the Mouse Genetics Programme (http://www.sanger.ac.uk/science/collaboration/mouse-resource-portal) and DNase treated. Stranded RNA-seq libraries were constructed using the Illumina TruSeq Stranded RNA protocol with oligo dT pulldown. Notes about samples and libraries: (1) A combination of litter identifier and embryo identifier within a litter will unambiguously identify a single embryo used in this study. (2) There is a margin of error for the somite-stage information (+/- 1 somite) because some embryos could be in between somite stages. (3) All knockouts in the parents or grandparents are for embryonic lethal genes. (4) There are four biological replicates per somite-stage, with the exception of the 4-somite embryos (three biological replicates only). Altogether 111 embryos were sourced, of which 14 were sequenced twice to generate enough read depth/coverage. No new libraries were prepared for the repeated sequencing, despite the assays being assigned new ERX* accessions. (5) Sex of the embryos was determined post-RNA-seq by looking at the expression of Xist (strong expression in females only). (6) Library constructon batch refers to batch of sample handling post RNA-extraction (size selection, PCR amplification during library preparataion). (7) Superbatch gathers 17 representative embryos out of the 111 embryos post RNA-extraction, and put them through the library construction pipeline as one single batch. The generated data is intended to be used for normalisation using the remove unwanted variation (RUV) method. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ .

Dataset Information

Whole embryo RNA-seq of 73 mouse mutant lines and baseline controls from the Mouse Genetics Project (DMDD)

Publications

Common and distinct transcriptional signatures of mammalian embryonic lethality.

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