The Genetics Podcast

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/)

This week on The Genetics Podcast, Patrick is joined by Dr. Brent Richards, CEO and Founder of 5 Prime Sciences and Professor of Human Genetics, Epidemiology, and Medicine at McGill University. They discuss how to triangulate different types of genetic evidence to validate a drug target, why herd psychology often drives which targets get funded, why strong genetic support didn't save the Zeus IL-6 trial, and how collider bias can distort genetically stratified clinical trials.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Brent
01:43 How company size shapes access to genetic drug discovery tools
04:10 Brent's framework for triangulating different types of genetic evidence
06:50 The herd psychology behind which drug targets get funded
10:01 Potential reasons the Zeus IL-6 trial failed despite strong genetic evidence
12:49 What a gold standard genetic evidence package actually looks like 
17:13 Closing the data gap with diverse genomes and systematic pipelines
19:03 The diabetes patient story that drove Brent into drug development and balancing academia with industry
25:39 Why obesity went from a drug development graveyard to its biggest frontier
29:13 How collider bias can distort genetic risk trial results
38:20 Where to go deeper on advanced genetic drug discovery concepts
40:11 Closing remarks
Find out more:
5PrimeSciences’ symposium on human genetics at ASHG2026 in October

This week on The Genetics Podcast, Patrick is joined by Dr. Andrew Jackson, Programme Leader at the MRC Human Genetics Unit at the University of Edinburgh. They discuss how his lab discovered that gain-of-function DNMT3A mutations cause both microcephalic dwarfism and an accelerated aging syndrome, and what that reveals about the shared biology of growth and aging.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Andrew
01:34 The origins of Andrew's work linking brain size and aging
02:54 The genetics of mammalian size range and epigenetic factors regulating growth
05:02 How DNMT3A mutations causing dwarfism led to discovering an accelerated aging syndrome
09:46 Cell number rather than cell size as the shared driver of growth and aging
13:07 Whether brain size within humans actually predicts cognitive ability
15:20 Why intellectual disability has far more known genes than dwarfism
19:26 Discovering ribonuclease H2's role in DNA repair, and its unexpected link to cancer 
23:35 Why studying rare monogenic diseases reveals broader biology
26:59 Andrew's next research questions on aging, cancer, and mutation biology
28:42 Why humans, model organisms, and cell assays each have a role
31:00 Somatic mosaicism's growing role in aging and disease beyond cancer
36:11 Closing remarks
Find out more:
Mentioned studies from Andrew’s lab: 
https://www.nature.com/articles/s41588-026-02633-8

https://www.nature.com/articles/s41588-018-0274-x

This week on The Genetics Podcast, Patrick is joined by Stevie Ringel, co-founder of Nome and founder of the Kizuna Foundation. They discuss Stevie's own ultra-rare disease diagnosis and shaped his path to founding Kizuna Foundation and Nome, how Nome's AI agents help scientists navigate the operational complexity of small-batch drug development, the technical and business model advantages underpinning Nome's accuracy, and what it will take to build a sustainable funding model for ultra-rare disease.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Stevie
01:37 Stevie's inherited retinal disease (IRD) diagnosis and subsequent path into genomics
03:16 Why Stevie founded Kizuna Foundation and why ultra-rare drug development is so operationally complex
06:27 The origin story of Nome and using AI to automate the operational work 
10:09 The inspiration for the name “Nome” and who the company is built to serve
12:44 The biggest blockers to program speed
15:07 How AI and scale can bring down the cost of gene therapy manufacturing
18:01 FDA signals and global regulatory competition 
19:33 Priority review vouchers and why Nome stays out of molecule IP
20:33 Nome's AI and review process for patient reports and its expansion to health systems
25:04 Nome's agent architecture and the data behind its accuracy
28:17 Why delivery remains gene therapy's biggest bottleneck and approaches for solving it
31:34 The case for a new capital model in rare disease drug development 
33:25 What’s next for Nome as they advance preclinical programs
34:25 Nome’s focus on process excellence across therapeutic modalities
36:34 Closing remarks
Find out more: Nome

This week on The Genetics Podcast, Patrick is joined by Dr. Jagesh Shah, Chief Scientific Officer at Mirai Bio. They discuss why delivery is a central bottleneck holding back nucleic acid medicines, how Mirai's lipid nanoparticle (LNP) platform is built to reach tissues like adipocytes and T cells, and the machine learning feedback loop the company uses to engineer LNP formulations.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Jagesh
01:40 Why delivery is the main bottleneck for gene therapies
03:42 Easier vs harder tissues to target for delivery
06:40 Overview of Mirai's modular delivery platform 
09:02 Comparing viral vectors and lipid nanoparticles (LNPs) 
12:18 Different approaches for targeting adipocytes and T cells with LNPs
15:49 Mirai's machine learning (ML) feedback loop for optimizing LNP formulation
20:50 Why lipid chemistry is still hard for ML to learn and factors affecting LNP tropism
24:35 Jagesh's path from academia to Mirai
27:23 Mirai's platform business model and how it lowers risk
29:13 What industry partnerships with Mirai look like
31:41 Mirai's next frontier of delivery to muscle tissue and the brain 
34:40 Cargo size and immunogenicity of LNPs vs AAV 
36:00 Why the field needs to close the regulatory pace gap 
37:19 Closing remarks
Find out more:
Mirai Bio