In the most recent episode of The Genetics Podcast, Sano CEO Dr. Patrick Short explored the latest discoveries in genetics and precision medicine with returning guest Dr. Veera Rajagopal. Dr. Veera, a scientist at Regeneron and quarterly guest on our podcast, provided insights into recent influential studies reshaping our understanding of genetic disorders and their implications for medical treatment.
Dr. Veera kicked off the discussion by highlighting a remarkable discovery in the field of neurodevelopmental disorders. Researchers from the University of Oxford and the Broad Institute, in collaboration with Genomics England, identified a recurrent de novo mutation in a small nuclear RNA gene that is a significant cause of neurodevelopmental disorders. This mutation is present in about 0.5% of all neurodevelopmental disorder cases, which translates to potentially thousands of families globally.
This discovery is groundbreaking for several reasons:
1. High recurrence of a rare mutation: The mutation, although de novo, is recurrent and extraordinarily common, making it a significant genetic cause of neurodevelopmental disorders.
2. Non-coding genome: The mutation is in a non-coding region, emphasizing the importance of non-coding areas in genetic research.
3. Therapeutic implications: This finding opens avenues for developing targeted treatments, given the large patient population affected by this single mutation.
The conversation then shifted to an exciting development in Parkinson's disease research. A recent study identified a gene, RAB32, that is directly linked to familial Parkinson's disease. This gene interacts with the well-known LRRK2 gene, a major player in Parkinson's disease. The discovery was made through an exome-wide association study that highlights the gene’s significance in the disease’s pathology.
Key points include:
1. Genetic interaction: RAB32’s interaction with LRRK2 opens new pathways for understanding the disease mechanism.
2. Drug development: The identification of RAB32 as a significant factor could influence new therapeutic strategies, potentially targeting both LRRK2 and RAB32.
Dr. Veera also shared insights on a recent study published in Nature Immunology, which identified variants in the UNC93B1 gene as a monogenic cause of early-onset systemic lupus erythematosus (SLE). This discovery was supported by parallel findings from research groups in China and Germany.
Here's why this discovery is significant:
Genetic understanding: Provides a deeper understanding of the genetic basis of early-onset lupus.
Therapeutic potential: Opens up new possibilities for targeted therapies using existing drugs that modulate TLR7 signaling, crucial for patients with these specific genetic variants.
The final discussion focused on recent advancements in Alzheimer’s disease research. A study on individuals carrying the APOE3 Christchurch variant provided further evidence and insights into how this variant might protect against Alzheimer's.
Highlights include:
1. Protective variant: The APOE3 Christchurch variant appears to delay the onset of cognitive impairment and offers protective effects even in heterozygous carriers.
2. Implications for therapy: This reinforces the potential of targeting APOE3 in therapeutic strategies, providing hope for more effective treatments for Alzheimer's disease.
This episode of The Genetics Podcast highlighted the rapid advancements in genetic research and their profound implications for precision medicine – from groundbreaking discoveries in neurodevelopmental disorders and Parkinson's disease to significant breakthroughs in early-onset lupus and Alzheimer's. We're already looking forward to having Dr. Veera on next quarter!
Don’t forget to check out Dr. Veera’s substack, GWAS Stories, and his Twitter, @doctorveera.