Transcriptomics

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Tissue specific transcriptional profiling of the consequences of 16p11.2 deletion and duplication in Mouse


ABSTRACT: 16p11.2 microdeletion/microduplication syndrome is one of the common genetic causes of autism spectrum disorder, although it is not wholly penetrant with a wide range of phenotypic manifestations. We have previously explored the transcriptional consequences of the copy number variant (CNV) in cortical tissue of mouse models of the CNV within the syntenic 7qF3 region (Blumenthal et al 2014). We found that the strongest effects were from genes within the region itself, with no evidence for dosage compensation for any gene. Importantly, we found that global transcriptional effects due to the CNV were associated with multiple hypotheses for ASD pathogenesis, at the level of individual genes, networks and functional enrichments. To delineate tissue-specificity effects of the CNV, we embarked on exploration of the transcriptional landscape across multiple tissues for all mice from our earlier study. Specifically to disentangle brain-specific effects from others, we chose two additional brain tissues, namely Cerebellum and Striatum, as well as three other non-neuronal tissues, namely Liver, White Fat and Brown Fat. We present strand-specific RNAseq data for these five tissues in addition to the data for the Cortical tissue from our previous publication. Preliminary analyses of the data suggest that there are strong tissue-specific consequences of the CNV, with the effect being strongest in the Cortical tissue relative to other tissues, and observe low overlaps in differentially expressed genes across tissue. Furthermore, we see that the genes within the CNV region behave in a strong-tissue specific manner, with differences being more pronounced among the neuronal and non-neuronal tissues, relative to within tissue classes. Interestingly, we see that in non-neuronal tissues dosage compensation occurs for a handful of genes, when expressed. Finally, we see that genes within the CNV region show the strongest effects relative to the overall transcriptome in neuronal tissues and these effects are ameliorated in non-neuronal tissues.

ORGANISM(S): Mus musculus

PROVIDER: GSE76872 | GEO | 2018/10/02

REPOSITORIES: GEO

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