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SRP067243
Mus musculus
20 Downloadable Samples
Illumina HiSeq 2000
Description
Analysis of the transcriptional changes in the heart resulting from the loss of cardiac enhancers. As there remains a limited understanding of the phenotypic consequences of enhancer mutations, we examined the impact of loss of function mutations by deleting two enhancers near heart disease genes in mice. In both cases, we observed loss of target gene expression, as well as cardiac phenotypes consistent with heart disease in humans, highlighting the functional importance of enhancers for normal heart function, as well as the potential contribution of enhancer mutations to heart disease. Overall design: Hearts were dissected from wild-type and enhancer-null mice (either embryonic or adult) and processed for deep RNA-seq analysis.
Publication Title
Genome-wide compendium and functional assessment of in vivo heart enhancers.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1 knockout mice displayed phenotypes similar to those observed on ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes. Overall design: Total RNA-seq from dissected regions of the digestive tract, from wild-type and percc1-/- mice.
Publication Title
Noncoding deletions reveal a gene that is critical for intestinal function.
Sample Metadata Fields
Specimen part, Subject
View Samples