Next Evonne McArthur will discuss "Personalised regulatory genomics: identifying gene dysregulation to solve undiagnosed rare disease cases" #ASHG20
UDM - undiagnosed diseases network. Genetic diagnosis approach resolves ~35% of diagnosis. These lead to changes in patient treatment and understanding of their diseases #ASHG20
Most genetic diagnosis is done through examining coding mutation, but increasingly interested in understanding (non-coding) variant effects on the transcriptome #ASHG20
Imputing gene regulation. TWAS methods build imputed expression profiles from observed genotypes and gene expression #ASHG20
Identifying gene dysregulation through TWAS. Use proband genotype to predict gene expression. Compare to reference population. Identify potentially dysregulated genes as those outlying compared to pop (or compared to parents if available) #ASHG20
Then seek to understand relevance of ID'd genes to phenotype. #ASHG20
E.g. 4 year old male with optic and developmental phenotypes. Dysregulation approach identified WFS1 as a potential gene - more extreme than biobank and parents. WFS1 associated with Wolfram syndrome (similar phenotypes to observed in child). #ASHG20
[Missed end of talk]
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