Next up is Jill Moore - talking about "Cell type-specific regulatory landscapes defined across murine brain development reveal novel biological insights for genetic variants associated with neuropsychiatric disorders" #ASHG20
ENCODE consortium recently published a dataset of candidate cis-regulatory elements across mouse and human genomes. Mouse data is unique because it was a coordinated effort across labs for 8 developmental stages and 12 tissues - enables integrative analysis #ASHG20
Mouse data matrix is much richer than for human. Keen to use mouse data to inform studies of human. See homologous CCREs, CCREs that map only, and CCREs that don't map. Most PLS[?] CCREs map to human genome. Distal enhancers map more poorly #ASHG20
Most conserved mouse brain cCREs are also active in foetal human brain. Can define regulatory landscapes in mouse, and then use these to inform human studies. #ASHG20
Temporal clustering of gene expression generates four sets (increase, dynamic increase, decrease, dynamic decrease). See consistency across tissues. Want to link enhancer-gene across cell types and species #ASHG20
Integrated snATAC-seq data to identify developmental stage-specific cell types. Used regulatory landscapes to annotate GWAS. #ASHG20
Applying to shared GWAS of ASD and SCZ, identified enrichments in neurons. Selected 16 targets for functional validation. 30% showed enhancer enhancer activity. #ASHG20
Focus on rs13031349 - putative causal variant for SCZ, lies in a genomic region only active in brain development. Lies in AGAP1 gene in human and mouse, but seems to act on GBX2 (closer TSS to variant). Need further evidence that GBX2 is the target #ASHG20
Alternative allele results in weaker enhancer activity in neural tube of mouse #ASHG20
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