The Genetics Podcast

Summary
This week on The Genetics Podcast, Patrick is joined by Jenny Hsieh, Co-Founder and President of the Danon Foundation. They discuss how Danon disease affects males and females, why it is so often misdiagnosed, the current therapy landscape and research priorities, and how families can make informed decisions about gene therapy trials.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Jenny 
01:28 An overview of Danon disease
02:34 Sex differences in Danon disease and severe disease in females
05:15 Why Danon disease is misdiagnosed and how it may be spotted earlier
08:50 Therapy pipeline for Danon and the Foundation's global patient coordination
13:46 Origin story of the Danon Foundation
18:10 Research priorities and the burden of Danon disease beyond the heart
22:39 Raising genetic testing awareness among ophthalmologists and cardiologists for Danon disease
25:20 Recognizing broader Danon symptoms and launching the first Danon Awareness Day
29:37 Informed consent and trial literacy for families weighing gene therapy
33:14 Patient-friendly trial experiences
36:19 Ways to support Danon research
37:37 Closing remarks
Find out more
Danon Foundation

This week on The Genetics Podcast, Patrick is joined by Dr. Inigo Martincorena, Group Leader at the Wellcome Sanger Institute. They discuss the discovery of widespread cancer-driver mutations in normal tissue, the role of somatic mutations in autoimmune disease, new sequencing technologies transforming the field, and the therapeutic potential of targeting these mutations.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Inigo 
01:46 How Inigo's eyelid skin study revealed widespread cancer-driver mutations
07:14 Findings from a follow-up study on esophageal tissue
10:02 How NanoSeq technology scaled somatic mutation research across tissues
12:34 The thyroid study linking somatic mutations to autoimmune disease
17:07 How escaped B cell clones evolve into polyclonal autoimmune disease
20:21 Immune gene mutations occurring in healthy aging lymphocytes
21:21 Why driver mutation clones in normal tissue rarely become cancer
24:16 Two therapeutic paradigms for targeting somatic mutations in disease
28:13 Examples of somatic rescue mutations in the colon, liver, and blood
29:20 Why clonal selection only occurs in dividing cell types
31:20 The field's remaining blind spots in mobile immune cells and rare samples
33:46 How new single-cell sequencing will link genotype to phenotype
36:03 What Inigo has learned from collaborating across Sanger's expertise
38:09 Closing remarks
Find out more
Eyelid study

Esophagus study

This week on The Genetics Podcast, Patrick is joined by Dr. Marleah Dean Kruzel, Professor of Communication at the University of South Florida. They discuss her personal path from watching breast cancer move through her family to testing positive for a hereditary mutation herself, the ART framework she developed for managing uncertainty, and the complexities of communicating genetic risk within families.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Marleah
01:35 Marleah's family history of breast cancer across four generations
02:48 Marleah's childhood living through her mother's five-year cancer battle
04:26 Marleah's experience with genetic testing
07:19 How a positive test result reshaped Marleah’s PhD research focus
08:40 The central challenges of living with a positive test result 
10:50 The ART framework for managing hereditary cancer uncertainty
15:06 Applying the ART framework to Patrick’s experience with uncertainty and the importance of having a support system 
19:53 Common misconceptions in how families communicate genetic risk
23:54 The previvor identity and the chronic uncertainty it brings
25:40 How Marleah has learned to accept and embrace uncertainty
27:57 Balancing logic and emotion in hereditary cancer family planning
31:28 How Marleah grounds her research tools in patients' lived experience
33:21 How AI is eroding our capacity to sit with uncertainty
35:57 Redesigning healthcare for a lifespan of genetic risk information
38:10 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Dr. David Hallett, Chief Scientific Officer at Recursion. They discuss the biggest shifts in drug discovery over Dave's three-decade career, where AI is genuinely transforming the field today versus where the hype outruns the reality, and how Recursion's perturbational maps have uncovered and validated a novel neurodegeneration target.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Dave
01:57 The biggest shifts in drug discovery over three decades
06:39 Where AI is delivering real wins across drug discovery today
12:19 How AI-assisted trial simulation reveals which eligibility criteria to relax
14:46 The three biggest reasons drug programs fail in the clinic 
18:20 How Recursion's perturbational maps uncover new drug targets
24:58 A four-step framework for validating a novel drug target
28:44 How Recursion balances deep therapeutic focus with partnership breadth
30:52 Why AI can't shortcut clinical trials, and what proof of real impact looks like
34:57 The skills scientists need most in the AI era, and why trusting AI outputs starts with trusting the data
39:52 Closing remarks
Find out more:
Recursion (https://www.recursion.com/)

This week on The Genetics Podcast, Patrick is joined by Dr. Danny Miller, Assistant Professor of Pediatrics and of Laboratory Medicine and Pathology at the University of Washington and Attending Physician at Seattle Children's Hospital. They discuss the case for making long-read sequencing the first genetic test every patient receives, the reference dataset his lab is building from the 1000 Genomes Project to resolve structural variants, publicly available methylation signatures as biomarkers for diagnosis and treatment response, and his vision for genome-informed care from newborn screening through the NICU.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Danny
01:41 The case for long-read sequencing as first-line genetic testing
02:52 Current barriers to wider use of long-read sequencing 
04:14 Building a long-read reference dataset from 1000 Genomes for variant filtering
06:47 How long-read sequencing can solve a missed diagnosis 
08:12 The clinical case for complete telomere-to-telomere genomes
10:39 What it will take to shift the clinical genetics status quo
12:06 Making methylation signatures public to diagnose disease and track therapy
15:58 Danny's path from programming and finance into clinical genetics
18:19 Danny's lived experience with deafness and achondroplasia, and how it shapes his approach to genetic counseling
21:46 Danny's optimism about AI in genomics and worry about AI in education
27:15 The path to making genomes a routine part of the medical record
29:47 The vision of same-day newborn genomic data guiding NICU treatment decisions
34:31 Closing remarks
Find out more:
Miller Lab (https://millerlaboratory.com/)