The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Dr. Glenn Cohen, Professor at Harvard Law School. They discuss the evolving legal and ethical landscape of reproductive genetics, why regulation in areas like embryo selection remains limited, and questions arising around the use of AI in healthcare.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Glenn01:35 An overview of the courses Glenn teaches at Harvard Law School02:29 Glenn’s areas of expertise across biomedical ethics03:20 Ethical considerations around reproductive medicine and polygenic risk scores10:37 Regulatory uncertainty and limited oversight in reproductive genetics13:18 Liability, regulation, and real-world implementation challenges for AI in healthcare14:52 Risk–benefit framework for evaluating AI use in clinical settings17:19 Glenn’s experience contributing to landmark Supreme Court cases in biotechnology and health law20:09 Glenn’s perspective on mitochondrial replacement and its regulatory divide between the UK and US22:20 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform!

This week on The Genetics Podcast, Patrick is joined by Dr. Andrea Ganna, Associate Professor at the Institute for Molecular Medicine Finland (FIMM). They discuss the promise and limits of polygenic risk scores for disease prediction and clinical trials, how large-scale electronic health records and AI models could transform medical research and healthcare planning, what Finland’s national health data infrastructure enables for population-scale studies, and how genetics can be used to strengthen trial emulation in observational data.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Andrea01:51 Andrea’s research focuses, including polygenic scores in biobanks and AI applications 03:02 Complementarity between polygenic scores and electronic health record–derived risk signals across biobanks04:47 Using polygenic risk scores for prognostic versus predictive enrichment in clinical trials10:28 Limitations and opportunities of using AI models on large-scale electronic health records15:47 Legal, data infrastructure, and privacy barriers to building AI models on health records18:04 Choosing model architectures for healthcare AI 19:47 Using AI and multi-omics data to integrate biological knowledge and the challenge of learning causality21:43 How removing genetic effects from proteins improves disease prediction and highlights the role of environment24:42 Finland’s health data ecosystem and national biobanks28:11 Using genetics to improve trial emulation in biobank data and observational studies33:42 Closing remarksFind out more:Trial emulation studyPolygenic scores studyPlease consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined by Dr. Anna Lindstrand, Professor and Consultant in Clinical Genetics and Genomics at the Karolinska Institute. They discuss how Sweden has scaled whole genome sequencing as a first-line test for rare disease, what long-read sequencing adds to clinical diagnostics, how national genomic infrastructure can accelerate translation into precision medicine, and where prevention and adult genomic screening may fit into the future of healthcare.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Anna01:34 Choosing between whole genome, exome, panels, and long-read sequencing in clinical practice04:05 Evaluating long-read sequencing in the clinic 06:37 What long-read sequencing adds to diagnostic yield09:15 The role of RNA sequencing, proteomics, and methylation profiling as complementary tools in clinical genomics13:07 Building a coordinated national infrastructure for clinical genomics and rare disease research in Sweden18:20 The shift toward precision therapeutics and new standards for clinical actionability23:18 Using national genomic data and registries to make Sweden trial-ready for precision therapies27:01 Moving beyond monogenic models to capture polygenic and borderline signals in clinical genomics30:44 Genomics for prevention including adult screening and pharmacogenomics36:23 Anna’s research priorities for the next phase of genomic medicine and structural variant discovery38:32 Closing remarksFind out more:Long-read sequencing studyMoving beyond monogenic disease paperPlease consider rating and reviewing us on your chosen podcast listening platform!

This week on The Genetics Podcast, Patrick is joined by Dr. Matthew Goldstein, CEO of jscreen. They discuss his journey from physician-scientist and biotech founder to leading a national nonprofit focused on preventive genetic screening, how a personal tragedy reshaped his mission around carrier screening and access, and what it will take to close the gap between the promise of genomics and its real-world implementation in healthcare.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Matthew01:41 Matthew’s path from an MD-PhD to founding a personalized cancer vaccine biotech09:06 From personal tragedy to leading jscreen to expand access to reproductive carrier screening 17:11 Purpose, grief, and how Matthew has led jscreen in honor of his daughter20:38 The implementation gap between genomic potential and real-world preventive screening 23:33 Nonprofit models, reimbursement barriers, and building sustainable access to preventive genetic screening28:27 Lessons from the Jewish community’s experience with Tay-Sachs and gaps in understanding33:05 Preconception carrier screening and the role of community in preventive health38:04 Closing remarksFind out more: jscreen

Caleb Lareau, computational genomics PI studying the human virome and sequencing methods, and Ryan Dhindsa, population geneticist focused on rare variants and disease mechanisms, discuss extracting Epstein–Barr virus signals from human genomes. They cover rescuing viral reads from WGS, validating EBV persistence in UK Biobank, links to autoimmune conditions, extending methods to the broader virome, and design needs for diverse population genomics.

This week on The Genetics Podcast, Patrick is joined by Dr. Nicky Whiffin, Associate Professor and Wellcome Career Development Fellow at the Big Data Institute, University of Oxford. They discuss the discovery of a new neurodevelopmental syndrome caused by mutations in the small nuclear RNA gene RNU4-2, what this reveals about the non-coding genome and the spliceosome, and how large-scale genome sequencing is reshaping diagnosis, variant interpretation, and the future of genetic medicine.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Nicky02:09 Overview of the non-coding genome and its functional elements03:59 How small nuclear RNAs drive splicing and exon recognition04:54 Overview of the major and minor spliceosomes and the role of small nuclear RNAs in intron removal06:34 Discovery of recurrent de novo RNU4-2 mutations in developmental disorders through large-scale genomics data12:18 Growth of patient advocacy groups and global networks following the discovery of ReNU syndrome14:43 Potential for antisense oligonucleotide therapies for ReNU syndrome16:06 Clinical endpoints, treatment timing, and biomarker development for ReNU18:32 Impact of RNU4-2 discovery on exome design, genome sequencing adoption, and targeted testing strategies19:52 Distinct dominant, recessive, and retinal phenotypes arising from variants within RNU4-222:15 Open questions on mutation rates and selection in spliceosomal small nuclear RNAs25:25  Limits of non-coding variant discovery and the unresolved genetic burden in developmental disorders29:52 Therapeutic upregulation strategies targeting untranslated regions in haploinsufficiency 33:40 The MRC Centre of Research Excellence in Therapeutic Genomics’ approach to scalable genetic medicines35:54 Long-term prospects and delivery challenges for gene editing approaches 36:56 Newborn genome screening, actionability debates, and implications for rare disease diagnosis40:25 Population genomics insights from unascertained newborn genome sequencing cohorts42:04 Closing remarksFind out more: ReNU discovery paper

Steven Gray, a pediatric professor engineering AAVs for CNS delivery, and David Dismuke, CTO scaling GMP AAV manufacturing, discuss translating AAV from lab to industry. They cover capsid engineering for brain delivery, manufacturing workflows and analytics, full versus empty particle impacts on safety, and how scale and platform choices could cut costs and enable next‑gen gene editing.

Daniel Chung, an ophthalmologist and CMO with 30+ years in ocular gene therapy including work on Luxturna. He recounts building the first approved ocular gene therapy. They discuss designing pivotal trials, choosing meaningful clinical endpoints, delivery and immunogenicity challenges, and strategies for treating earlier patients and larger genes.

Zornitza Stark, clinical geneticist and translational genomics leader at the University of Melbourne, talks genomic newborn screening and rapid sequencing. She describes the BabyScreen+ pilot, scaling challenges like automation and AI for variant curation, family-wide cascade testing and psychosocial needs, gene-selection criteria, equity and representativeness concerns, and the infrastructure and policy needed for national programs.

Join Michelle Werner, CEO of Alltrna, who focuses on engineered tRNA therapeutics for rare genetic diseases, and Mike Severino, CEO of Tessera Therapeutics, specializing in RNA-based gene-writing platforms. They discuss how 2026 is a pivotal year for clinical trials, share groundbreaking preclinical results, and explore innovative strategies for addressing genetic mutations. The duo also highlights the importance of patient advocacy and the adaptability of their platforms to tackle various genetic disorders, marking a promising future in genetic medicine.