In the latest episode of The Genetics Podcast, Patrick welcomes back Dr. Veera Rajagopal, a drug discovery scientist at Regeneron, for his quarterly discussion about the latest breakthroughs in genetic research. Together, they take a close look at some of the most exciting papers from the past few months, focusing on evolutionary genetics, structural variants, and new research into disease mechanisms.
Kicking off the discussion, Patrick and Dr. Veera explore a recent paper from Harvard Medical School, which highlights the role of structural variants in genome-wide association signals. The paper reveals how a transposon—a type of "jumping gene"—drives genetic variation related to pigmentation and skin cancer risk.
“This is a fascinating evolutionary story,” says Dr. Veera, as he walks through the study’s findings. The research shows how a transposon near the ASIP gene, long linked to pigmentation traits, likely arose after humans split from Neanderthals, contributing to lighter skin pigmentation in European populations. Dr. Veera notes that this discovery shows how much is still left to be learned from existing genetic data, and says that it suggests many genome-wide association loci remain unsolved mysteries.
The conversation then shifts to a paper from Baylor College of Medicine that focuses on Alzheimer's disease. Dr. Veera and Patrick discuss how this study uncovers a previously underappreciated tau protein isoform—Big Tau—that is resistant to the kinds of aggregations linked to neurodegenerative conditions like Alzheimer’s.
In a detailed breakdown, Dr. Veera explains how Big Tau appears to play a protective role in regions of the brain that are typically spared by Alzheimer’s disease. He points out that the discovery of this isoform could pave the way for new treatment approaches, potentially even allowing scientists to use this isoform to prevent or slow neurodegeneration.
Another study highlighted in this episode involved research from Rockefeller University, where scientists identified a genetic mutation in the TMF1 gene that makes individuals more susceptible to herpes simplex encephalitis. This study was particularly interesting as it demonstrated a previously unknown role of this gene in protecting neurons from viral infections.
“The discovery of human knockouts for TMF1 who are highly susceptible to herpes encephalitis is one of the most exciting findings in viral genetics,” says Dr. Veera. He notes how this discovery opens up new options for antiviral therapies, potentially leading to treatments that could protect people from severe brain infections by mimicking the protective role of TMF1.
The conversation then led on to another study about a novel cardiac arrhythmia syndrome caused by a non-coding variant. Researchers at Oxford identified a rare, non-coding deletion-insertion variant that acts like a de novo enhancer, triggering abnormal potassium channel activity in the heart. This research provides new information to help understand the non-coding genome’s role in disease and could also potentially lead to more treatments for arrhythmias in the future.
Throughout the episode, Dr. `Veera emphasizes that we are only scratching the surface of what’s possible in genetics. Both he and Patrick stress the importance of continuing to push the boundaries, particularly in understanding non-coding regions and leveraging genetic diversity beyond European populations.
As the episode draws to a close, Patrick and Dr. Veera hint at more exciting discoveries on the horizon, including Dr. Veera’s upcoming work on non-European genetics. With ongoing advancements in sequencing technology and a growing understanding of the non-coding genome, there will be plenty more interesting discoveries over the next few months, so stay tuned for more insights with Dr. Veera at the end of the year.
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