Investigating the Role of Genotypic Structural Variants on Hyper-Social Behavioral Phenotypes in Canine Model Organisms

Abstract

The presence of structural variants in the WBS region of canine chromosome 6 has been associated with hyper-social behavioral phenotypes in canines. This region has an adjacent orthologous region in the human genome which is implicated in Williams–Beuren Syndrome, a neurocognitive condition also prominently characterized by hyper-sociability. While the correlation of structural variants at four key loci in the WBS region and hyper-social behavioral phenotypes has been established, the molecular mechanisms and biological pathways underlying this association have remained largely unclear. Given the molecular, medical, and evolutionary implications of this region, this project investigates how the presence of structural variants at the target loci affects gene expression and exon splicing patterns in order to better understand the regulatory mechanisms driving this phenotypic difference. Differential expression of two reverse transcriptase domain-containing proteins was found in association with an insertion at the GTF2I Cfa6.66 locus, suggesting potential regulation via changes in downstream transposon integration. Under-expression of a snoRNA transcript was found in association with an insertion at the WBSCR17 Cfa6.7 loci, implying altered downstream alternative splicing patterns and potential changes in rRNA methylation. Over-expression of a mtRNA transcript was associated with a deletion at the POM121 Cfa6.83 locus, suggesting potential regulatory interactions between the nuclear and mitochondrial genome. No evidence for alternative splicing at the target loci was found.