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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

00:23:28

348: v96: A 96-mutation plasma DNA test to track...

Base by Base ·

2026/04/21

Wang Y et al et al., PNAS - This episode covers a PNAS study describing v96, a personalized plasma cell-free DNA assay that tracks up to 96 patient-specific mutations to sensitively quantify measurable residual disease (MRD) in AML patients before and after allogeneic hematopoietic cell transplantation. Key terms: cell-free DNA, measurable residual disease, acute myeloid leukemia, hematopoietic cell transplantation, duplex sequencing. Study

en-us

00:23:30

347: Diffusive spreading across dynamic mitochondrial...

Base by Base ·

2026/04/19

Holta KB et al., Proceedings of the National Academy of Sciences (PNAS) - This episode explains a quantitative framework for diffusion on spatially embedded dynamic mitochondrial networks. The study combines analytic theory, agent-based simulations, and live-cell imaging to show how connectivity, fusion/fission, and mobility set biomolecular mixing on mitochondrial populations. Key terms: mitochondria, diffusion, intracellular transport, temporal

en-us

00:23:19

346: Palindromes and RNA Self-Recognition

Base by Base ·

2026/04/19

Kimchi O et al., PNAS - This computational study shows that self-complementary RNA regions (palindromes) can drive sequence-specific homotypic clustering by enabling multivalent intermolecular base pairing, and that Drosophila nanos and pgc mRNAs are enriched for accessible, strong palindromes. Key terms: RNA palindromes, homotypic clustering, germ granules, nanos mRNA, phase separation. Study Highlights:The authors use equilibrium and nonequilibrium in

en-us

00:25:41

345: Genes of Prosody: Rhythm, Music, and Reading

Base by Base ·

2026/04/17

Scartozzi AC et al., Human Genetics and Genomics Advances - This episode reviews a GWAS of speech rhythm (prosody) perception using the TOPsy task (n≈1,501 European-ancestry), reporting 14 suggestive loci, nominal enrichment for songbird vocal-learning gene sets, and polygenic links to reading and musical rhythm. Key terms: prosody, speech rhythm, genetics, musical rhythm, reading. Study Highlights:The authors performed a GWAS of TOPsy speech rhythm

en-us

00:25:41

345: Genes of Prosody: Rhythm, Music, and Reading

Base by Base ·

2026/04/17

Scartozzi AC et al., Human Genetics and Genomics Advances - This episode reviews a GWAS of speech rhythm (prosody) perception using the TOPsy task (n≈1,501 European-ancestry), reporting 14 suggestive loci, nominal enrichment for songbird vocal-learning gene sets, and polygenic links to reading and musical rhythm. Key terms: prosody, speech rhythm, genetics, musical rhythm, reading. Study Highlights:The authors performed a GWAS of TOPsy speech rhythm

en-us

00:23:28

344: Homozygous TNNI3 p.Arg136* and severe pediatric...

Base by Base ·

2026/04/17

Kühnisch J et al., Human Genetics and Genomics Advances 7, 100598 (2026) - Case report and tissue analysis linking a homozygous TNNI3 nonsense variant (c.406C>T; p.Arg136*) to early-onset, treatment-refractory restrictive cardiomyopathy in a young child who required heart transplantation. Key terms: TNNI3, restrictive cardiomyopathy, pediatric cardiomyopathy, troponin I, protein truncation. Study Highlights:A 2-year-old female with severe pediatric

en-us

00:13:48

343: From Cats to Dogs: The Parvovirus Host Jump

Base by Base ·

2026/04/15

López-Astacio RA et al., PNAS - Analysis of 60 years of feline panleukopenia virus genomes traces the origins of canine parvovirus, identifies vaccine-derived sequences, and documents distinct evolutionary rates and capsid adaptations that enabled a host jump to dogs. Key terms: parvovirus, FPV, CPV, host jump, evolution. Study Highlights:Using full-genome sequencing and phylogenetics, the authors compare 60 years of FPV evolution with 47 years of CPV

en-us

00:13:48

343: From Cats to Dogs: The Parvovirus Host Jump

Base by Base ·

2026/04/15

López-Astacio RA et al., PNAS - Analysis of 60 years of feline panleukopenia virus genomes traces the origins of canine parvovirus, identifies vaccine-derived sequences, and documents distinct evolutionary rates and capsid adaptations that enabled a host jump to dogs. Key terms: parvovirus, FPV, CPV, host jump, evolution. Study Highlights:Using full-genome sequencing and phylogenetics, the authors compare 60 years of FPV evolution with 47 years of CPV

en-us

00:17:24

342: Modular MPRA Reveals Context-Dependent...

Base by Base ·

2026/04/14

Tovar A et al., Human Genetics and Genomics Advances - This episode examines a study that used a modular MPRA to test ~11,656 genomic fragments from T2D- and metabolic trait-associated regions in pancreatic beta cells, comparing upstream vs downstream positions and SCP1 vs INS promoters. The work identifies promoter- and position-dependent regulatory activity and implicates HNF1 motifs in INS promoter-specific effects. Key terms: massively parallel

en-us

00:17:24

342: Modular MPRA Reveals Context-Dependent...

Base by Base ·

2026/04/14

Tovar A et al., Human Genetics and Genomics Advances - This episode examines a study that used a modular MPRA to test ~11,656 genomic fragments from T2D- and metabolic trait-associated regions in pancreatic beta cells, comparing upstream vs downstream positions and SCP1 vs INS promoters. The work identifies promoter- and position-dependent regulatory activity and implicates HNF1 motifs in INS promoter-specific effects. Key terms: massively parallel

en-us

00:29:43

341: The Genetic Lottery and the Value of an Extra...

Base by Base ·

2026/04/13

Widding-Havneraas T et al., PNAS - This study uses genetic variation related to educational attainment as a quasi-experimental instrument (Mendelian randomization) together with Norwegian registry data to estimate the causal return to an additional year of schooling on labor-market earnings. Key terms: returns to education, Mendelian randomization, polygenic index, Norwegian registries, life-cycle earnings. Study Highlights:The authors triangulate OLS,

en-us

00:17:01

340: Microexon Control of Behavior — PTPRD Splicing

Base by Base ·

2026/04/12

Imai A et al., Proceedings of the National Academy of Sciences (PNAS) - This paper shows that alternative splicing of a 12-nt microexon (meB) in Ptprd is regulated by a genetic intronic enhancer and an activity-dependent intronic silencer to set region- and age-specific ratios of PTPRD splice variants. Manipulating these intronic elements in mice changes the proportion of meB-containing isoforms without altering total PTPRD protein and produces distinct

en-us

00:17:01

340: Microexon control of behavior: PTPRD splicing...

Base by Base ·

2026/04/12

Imai A et al., Proceedings of the National Academy of Sciences (PNAS) - This paper shows that alternative splicing of a 12-nt microexon (meB) in Ptprd is regulated by a genetic intronic enhancer and an activity-dependent intronic silencer to set region- and age-specific ratios of PTPRD splice variants. Manipulating these intronic elements in mice changes the proportion of meB-containing isoforms without altering total PTPRD protein and produces distinct

en-us

00:22:39

339: cxt: A language model for population genetics

Base by Base ·

2026/04/11

Korfmann K et al., Proceedings of the National Academy of Sciences (PNAS) - This episode examines cxt, a decoder-only transformer that performs next-coalescence prediction by translating local mutational context into pairwise TMRCA estimates. Trained on stdpopsim simulations, cxt delivers rapid, scalable coalescence-time inference, calibrated posteriors, and practical adaptations for empirical data. Key terms: language models, coalescent theory,

en-us

00:21:40

338: WDHD1 and Microcephalic Primordial Dwarfism

Base by Base ·

2026/04/10

Tibbe D et al., The American Journal of Human Genetics - This study identifies bi-allelic hypomorphic WDHD1 variants in 17 subjects with a clinical spectrum from fetal lethality to microcephalic primordial dwarfism and characterizes cellular defects in patient-derived cells linked to replisome dysfunction. Key terms: WDHD1, microcephalic primordial dwarfism, replication stress, sister chromatid cohesion, splicing variants. Study Highlights:Researchers

en-us

338: WDHD1 and Microcephalic Primordial Dwarfism

Base by Base ·

2026/04/10

Tibbe D et al., The American Journal of Human Genetics - This study identifies bi-allelic hypomorphic WDHD1 variants in 17 subjects with a clinical spectrum from fetal lethality to microcephalic primordial dwarfism and characterizes cellular defects in patient-derived cells linked to replisome dysfunction. Key terms: WDHD1, microcephalic primordial dwarfism, replication stress, sister chromatid cohesion, splicing variants. Study Highlights:Researchers

en-us

00:22:39

337: ND-CNVs and internalizing–cardiometabolic...

Base by Base ·

2026/04/08

Katzourou IK et al., The American Journal of Human Genetics 113, 1–11, June 4, 2026 - Population analysis of ~459,000 UK Biobank participants shows that carriers of neurodevelopmental CNVs (ND-CNVs) have higher odds of co-occurring internalizing (depression, anxiety, somatic) and cardiometabolic conditions (hypertension, dyslipidemia, obesity, T2D, CKD). Effects are stronger for deletions than duplications, greater in females, and linked to the number of

en-us

00:24:29

336: Measuring disease likelihood in genomic...

Base by Base ·

2026/04/07

Sapp JC et al., The American Journal of Human Genetics - A longitudinal study of recipients of medically actionable secondary genomic findings develops a Bayesian approach that integrates variant, family genotypic, and phenotypic data to estimate the probability that a secondary finding represents a true clinicomolecular diagnosis, with a detailed analysis of BRCA1/BRCA2 families and implications for screening policy and clinical management. Key terms:

en-us

00:24:29

336: Measuring disease likelihood in genomic...

Base by Base ·

2026/04/07

Sapp JC et al., The American Journal of Human Genetics - A longitudinal study of recipients of medically actionable secondary genomic findings develops a Bayesian approach that integrates variant, family genotypic, and phenotypic data to estimate the probability that a secondary finding represents a true clinicomolecular diagnosis, with a detailed analysis of BRCA1/BRCA2 families and implications for screening policy and clinical management. Key terms:

en-us

00:23:54

335: Altai Neandertal Genome Reveals Deep Population...

Base by Base ·

2026/04/05

Massilania D et al., PNAS - We summarize a PNAS study reporting a ~37× genome from a ~110,000-year-old male Neandertal (Denisova 17) from Denisova Cave. The genome shows D17 is closely related to an earlier Denisova Neandertal (D5), both carry Denisovan introgressed segments, and Neandertal groups displayed high regional differentiation and small, isolated populations in the Altai. Key terms: Neandertal, Denisova Cave, genome sequencing, population

en-us

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