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PODCAST

Base by Base

Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

science life sciences

All Episodes

00:14:52

🎙️ Episode 24: The Role of the X Chromosome in...

Base by Base ·

2025/05/18

🎙️ Episode 24: The Role of the X Chromosome in Complex Trait Genetics — Unraveling Dosage-Compensation Mechanisms🧬 In this installment of Base por Base, we delve into groundbreaking work by Fu et al. (2025) in The American Journal of Human Genetics, which systematically interrogates how the X chromosome shapes human quantitative traits. Leveraging data from over 350,000 UK Biobank participants with replication in more than 400,000 FinnGen individuals, the study quantifies the X chromosome’s

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00:14:11

🎙️ Episode 23: Evaluating the Return of Additional...

Base by Base ·

2025/05/17

🎙️ Episode 23: Evaluating the Return of Additional Findings from the 100,000 Genomes Project — Participant Experiences of Secondary Genomic Findings🧬 In this episode of Base por Base, we explore a mixed-methods study by Stafford-Smith et al. (2025) published in Genetics in Medicine, which examines how participants in England’s 100,000 Genomes Project experienced the disclosure of additional (secondary) genomic findings. By combining a cross-sectional survey of 147 adults who received either

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00:14:12

️ 23: Evaluating the Return of Additional Findings...

Base by Base ·

2025/05/17

️ Episode 23: Evaluating the Return of Additional Findings from the 100,000 Genomes Project — Participant Experiences of Secondary Genomic Findings In this episode of Base por Base, we explore a mixed-methods study by Stafford-Smith et al. (2025) published in Genetics in Medicine, which examines how participants in England’s 100,000 Genomes Project experienced the disclosure of additional (secondary) genomic findings. By combining a cross-sectional survey

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00:16:24

️ 22: Immune Sensing Unveiled — Ribonuclease Control...

Base by Base ·

2025/05/16

️ Episode 22: Immune Sensing Unveiled — Ribonuclease Control of Naked Extracellular RNA In this episode of Base por Base, we explore a landmark study by Castellano et al. (2025) published in Cell Genomics that uncovers how extracellular ribonucleases regulate the immune detection and functional uptake of naked extracellular RNA (exRNA). Through strategic use of a broad-spectrum ribonuclease inhibitor, the authors demonstrate that, contrary to long-held

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00:16:23

🎙️ Episode 22: Immune Sensing Unveiled — Ribonuclease...

Base by Base ·

2025/05/16

🎙️ Episode 22: Immune Sensing Unveiled — Ribonuclease Control of Naked Extracellular RNA🧬 In this episode of Base por Base, we explore a landmark study by Castellano et al. (2025) published in Cell Genomics that uncovers how extracellular ribonucleases regulate the immune detection and functional uptake of naked extracellular RNA (exRNA). Through strategic use of a broad-spectrum ribonuclease inhibitor, the authors demonstrate that, contrary to long-held assumptions, naked exRNAs can be

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00:17:05

️ 21: High-Throughput Variant Discovery — Pooled...

Base by Base ·

2025/05/16

️ Episode 21: High-Throughput Variant Discovery — Pooled Prime Editing in Human Cells In this episode of Base by Base, we explore a cutting-edge platform for scalable functional screening of human genetic variants reported by Herger et al. (2025) in Cell Genomics. The study introduces a pooled prime editing workflow in haploid HAP1 cells that optimizes pegRNA scaffold design, employs co-selection via an ATP1A1 resistance mutation, and integrates surrogate

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00:17:04

🎙️ Episode 21: High-Throughput Variant Discovery —...

Base by Base ·

2025/05/16

🎙️ Episode 21: High-Throughput Variant Discovery — Pooled Prime Editing in Human Cells🧬 In this episode of Base by Base, we explore a cutting-edge platform for scalable functional screening of human genetic variants reported by Herger et al. (2025) in Cell Genomics. The study introduces a pooled prime editing workflow in haploid HAP1 cells that optimizes pegRNA scaffold design, employs co-selection via an ATP1A1 resistance mutation, and integrates surrogate targets to enrich and filter highly

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00:15:29

️ 20: Genotype-Specific Chemoprevention with...

Base by Base ·

2025/05/16

️ Episode 20: Genotype-Specific Chemoprevention with Sulfadoxine-Pyrimethamine In this episode of Base by Base, we examine a comprehensive analysis by Mousa et al. (2025) in Nature Communications that quantifies how mutations in the Plasmodium falciparum dihydropteroate synthase (dhps) gene affect the duration of protection conferred by sulfadoxine-pyrimethamine (SP) chemoprevention across Africa. A Bayesian multi-strain model was applied to reinfection

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00:15:28

🎙️ Episode 20: Genotype-Specific Chemoprevention with...

Base by Base ·

2025/05/16

🎙️ Episode 20: Genotype-Specific Chemoprevention with Sulfadoxine-Pyrimethamine🧬 In this episode of Base by Base, we examine a comprehensive analysis by Mousa et al. (2025) in Nature Communications that quantifies how mutations in the Plasmodium falciparum dihydropteroate synthase (dhps) gene affect the duration of protection conferred by sulfadoxine-pyrimethamine (SP) chemoprevention across Africa. A Bayesian multi-strain model was applied to reinfection data from seven therapeutic efficacy

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00:18:18

️ 19: Systematic Identification of Promoter and UTR...

Base by Base ·

2025/05/14

️ Episode 19: Systematic Identification of Promoter and UTR Variants in Rare Disease Diagnostics In this episode of Base by Base, we delve into Martin-Geary et al.’s (2025) innovative framework for uncovering disease-causing variants within promoters and untranslated regions (UTRs) in individuals with rare disorders. Leveraging genome sequencing data from 8,040 undiagnosed trios in the Genomics England 100,000 Genomes Project, the authors combine precise

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00:18:16

🎙️ Episode 19: Systematic Identification of Promoter...

Base by Base ·

2025/05/14

🎙️ Episode 19: Systematic Identification of Promoter and UTR Variants in Rare Disease Diagnostics🧬 In this episode of Base by Base, we delve into Martin-Geary et al.’s (2025) innovative framework for uncovering disease-causing variants within promoters and untranslated regions (UTRs) in individuals with rare disorders. Leveraging genome sequencing data from 8,040 undiagnosed trios in the Genomics England 100,000 Genomes Project, the authors combine precise region definitions based on MANE

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00:25:14

️ 18: Bi-allelic UGGT1 Variants Define a Distinct...

Base by Base ·

2025/05/13

️ Episode 18: Bi-allelic UGGT1 Variants Define a Distinct Congenital Disorder of Glycosylation In this episode of PaperCast Base by Base, we explore the identification of bi-allelic variants in the UGGT1 gene as the cause of a novel congenital disorder of glycosylation characterized by neurodevelopmental impairment, seizures, dysmorphic features, and multiorgan involvement within the broader landscape of gene–disease associations and variant

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00:25:13

🎙️ Episode 18: Network Causality — A New Bayesian...

Base by Base ·

2025/05/13

🎙️ Episode 18: Network Causality — A New Bayesian Model for Multivariable Mendelian Randomization🧬 In this episode of Base by Base, we examine the methodological breakthrough presented by Liu et al. (2025) in Nature Communications. The authors introduce BayesMRnet, a Bayesian causal graphical model designed to perform joint Mendelian randomization (MR) across multiple exposures and outcomes. By leveraging genome-wide association study (GWAS) data, BayesMRnet constructs directed acyclic graphs

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00:20:17

🎙️ Episode 17: The Structure of Human Sweetness —...

Base by Base ·

2025/05/13

🎙️ Episode 17: The Structure of Human Sweetness — Cryo-EM of the TAS1R2+TAS1R3 Sweet Taste Receptor🧬 In this episode of Base por Base, we explore a landmark cryo-electron microscopy study by Juen et al. (2025) published in Cell, which reveals the high-resolution structure of the human sweet taste receptor heterodimer TAS1R2+TAS1R3 bound to the artificial sweeteners sucralose and aspartame, providing the first detailed view of how a single receptor recognizes a diverse array of sweet compounds.🔍

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00:20:18

️ 17: The Structure of Human Sweetness — Cryo-EM of...

Base by Base ·

2025/05/13

️ Episode 17: The Structure of Human Sweetness — Cryo-EM of the TAS1R2+TAS1R3 Sweet Taste Receptor In this episode of Base por Base, we explore a landmark cryo-electron microscopy study by Juen et al. (2025) published in Cell, which reveals the high-resolution structure of the human sweet taste receptor heterodimer TAS1R2+TAS1R3 bound to the artificial sweeteners sucralose and aspartame, providing the first detailed view of how a single receptor

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00:15:52

️ 16: Equity in Focus: Building a Truly Global...

Base by Base ·

2025/04/25

️ Episode 16: Equity in Focus: Building a Truly Global Genomic Landscape In this episode of Base by Base, we address one of the most pressing issues in human genomics: the need to close the ancestral data gap. Published in Cell Genomics, this commentary by Ana Luiza Arruda, Andrew Morris, and Eleftheria Zeggini calls attention to how genomic medicine remains disproportionately centered on individuals of European ancestry—jeopardizing its promise of

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00:13:04

🎙️ Episode 16: Equity in Focus: Building a Truly...

Base by Base ·

2025/04/25

🎙️ Episode 16: Equity in Focus: Building a Truly Global Genomic Landscape🧬 In this episode of Base by Base, we address one of the most pressing issues in human genomics: the need to close the ancestral data gap. Published in Cell Genomics, this commentary by Ana Luiza Arruda, Andrew Morris, and Eleftheria Zeggini calls attention to how genomic medicine remains disproportionately centered on individuals of European ancestry—jeopardizing its promise of precision health for all.The authors highlight

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00:20:07

️ 15: What Makes Us Human? Genetics from Neandertals...

Base by Base ·

2025/04/25

️ Episode 15: What Makes Us Human? Genetics from Neandertals to Now In this episode of Base by Base, we travel back in time—over 600,000 years—to explore the genomic storylines of Neandertals, Denisovans, and modern humans. Published in Cell by Hugo Zeberg, Mattias Jakobsson, and Nobel Laureate Svante Pääbo, this comprehensive review deciphers the evolutionary divergences that defined—and continue to define—our species.By comparing high-quality genomes

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00:35:32

🎙️ Episode 15: What Makes Us Human? Genetics from...

Base by Base ·

2025/04/25

🎙️ Episode 15: What Makes Us Human? Genetics from Neandertals to Now🧬 In this episode of Base by Base, we travel back in time—over 600,000 years—to explore the genomic storylines of Neandertals, Denisovans, and modern humans. Published in Cell by Hugo Zeberg, Mattias Jakobsson, and Nobel Laureate Svante Pääbo, this comprehensive review deciphers the evolutionary divergences that defined—and continue to define—our species.By comparing high-quality genomes from extinct and extant human lineages, the

en-us

00:25:44

️ 14: Beyond the Genome - Societal Value of National...

Base by Base ·

2025/04/25

️ Episode 14: Beyond the Genome: Societal Value of National Genomics Programmes In this episode of Base by Base, we discuss a thought-provoking report published in the European Journal of Human Genetics that tackles a crucial yet underexplored question: what is the actual value of large-scale national genomic programmes for society?Led by Ruth Horn, Angeliki Kerasidou, Jennifer Merchant and the UK-FR+GENE consortium, this multidisciplinary workshop

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