EP 239: What long-read sequencing reveals about Alzheimer’s and ALS with Paul Valdmanis of the University of Washington

This week on The Genetics Podcast, Patrick is joined by Dr. Paul Valdmanis, Associate Professor at the University of Washington. They discuss the impact of APOE4 on risk in Alzheimer’s disease, how long-read sequencing is uncovering hidden genetic variation in Alzheimer’s and ALS, and what rare variants and cryptic splicing can teach us about neurodegeneration.

Show Notes

0:00 Intro to The Genetics Podcast

01:00 Welcome to Paul

01:40 Long-read sequencing and ancestry-specific APOE4 risk in Alzheimer’s disease

04:20 Key findings from Paul’s study on a protective APOE4-linked variant in Alzheimer’s disease

10:58 What rare PSEN1 and PSEN2 variants reveal about Alzheimer’s disease biology

14:38 Disease-specific genetic mechanisms in ALS versus Alzheimer’s

17:14 Precision therapies for neurodegenerative disease

18:35 Choosing therapeutic targets in the neurodegenerative disease cascade

20:21 Landscape of ALS and Alzheimer’s therapies 

23:48 Lessons from liver-directed gene therapy on microRNA toxicity, cancer risk, and brain delivery challenges

29:12 Using long-read sequencing to uncover tandem repeat expansions missed by conventional genomics

33:26 Findings from a study of long-read sequencing on ancient genomes

38:06 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Find out more:

• APOE study

• Ancestry study