The Genetics Podcast

EP 144: Q2 Insights with Dr. Veera Rajagopal: Genetic mutations and their impact on disease research

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Episode notes

• This pathogenic variant escaped notice for years because it was not located in a protein coding region of the genome
• It now shows potential as a target for various therapeutic developments for children with developmental disorders 
• See the original paper here: De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

• Direct interactions with the LRRK2 gene through its armadillo domain, resulting in a gain of function missense mutation
• How RAB32 was discovered as a significant mutation in PD research
• The strong therapeutic implications of RAB32 and LRRK2
• See original papers: RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses and Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson’s disease

• Making discoveries by following a biological thread, a rare privilege enjoyed by few fields like immunology
• See original paper here: Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus
• A related paper from two years ago on SLE and the TLR7 gene: TLR7 gain-of-function genetic variation causes human lupus

• Redefining research goals to make better sense of old discoveries, in addition to making new discoveries
• deCODE’s previous work on the homozygosity deficit inference 
• APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease
• Homozygosity for R47H in TREM2 and the Risk of Alzheimer’s Disease