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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...more

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Latest Episodes

295: CFTR deltaF508 and CF-risk variants protect against IBD in large exome study

Episode 295

February 19, 2026

295: CFTR deltaF508 and CF-risk variants protect against IBD in large exome study

Yu M et al., Cell Genomics, 6 (2026) 101071. doi:10.1016/j.xgen.2025.101071 - Large-scale exome sequencing shows CFTR risk variants, including deltaF508, reduce susceptibility to inflammatory...

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00:28:25

294: Alternative splicing, exonization and lineage-specific isoforms: PTBP1, MAPT and TE-derived exons in mammalian evolution

Episode 294

February 18, 2026

294: Alternative splicing, exonization and lineage-specific isoforms: PTBP1, MAPT and TE-derived exons in mammalian evolution

Hunter CE et al., The EMBO Journal, doi:10.1038/s44318-025-00666-z - Review shows how alternative splicing, via TE exonization and cis-regulatory changes and revealed by long-read...

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00:36:58

293: IndeLLM (ESM2) zero-shot scoring and Siamese transfer learning for in-frame indel prediction (MCC 0.77)

Episode 293

February 17, 2026

293: IndeLLM (ESM2) zero-shot scoring and Siamese transfer learning for in-frame indel prediction (MCC 0.77)

Gracia Carmona O et al., Patterns, 7 (2026) 101425. doi:10.1016/j.patter.2025.101425 - IndeLLM uses protein language models (ESM2) to score in-frame indels and a compact...

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00:17:53

292: INS R6C signal-peptide defect reduces preproinsulin ER translocation in iPSC-derived βcells

Episode 292

February 17, 2026

292: INS R6C signal-peptide defect reduces preproinsulin ER translocation in iPSC-derived βcells

Tong Y et al., EMBO Molecular Medicine, doi:10.1038/s44321-025-00362-9 - Patient data, population genetics and iPSC-derived βcell models show INS R6C impairs preproinsulin ER translocation...

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00:17:09

290: SMN1 p.Arg288AlafsTer5 exon 7 deletions evade PCR newborn screening yet yield functional SMN isoform

Episode 290

February 15, 2026

290: SMN1 p.Arg288AlafsTer5 exon 7 deletions evade PCR newborn screening yet yield functional SMN isoform

Wirth B et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2026.01.012 - Two SMN1 exon 7 4-bp deletions (p.Arg288AlafsTer5) evade standard PCR...

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00:19:14

291: Dated gene duplications show Asgard archaeal host complexity before mitochondrial endosymbiosis

Episode 291

February 15, 2026

291: Dated gene duplications show Asgard archaeal host complexity before mitochondrial endosymbiosis

Kay CJ et al., Nature, doi:10.1038/s41586-025-09808-z - Relaxed-clock dating of pre-LECA gene duplications in Asgard archaeal and alphaproteobacterial lineages shows a complex archaeal host...

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00:06:39

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