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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

277: MDGA2 homozygous loss-of-function variants in developmental and epileptic encephalopathy

Episode 277

February 01, 2026

277: MDGA2 homozygous loss-of-function variants in developmental and epileptic encephalopathy

Morsy H et al., The American Journal of Human Genetics - Exome sequencing identifies homozygous MDGA2 loss-of-function variants in nine individuals and functional neuronal...

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00:18:27

276: AlphaGenome: 1-Mb multimodal deep model predicts regulatory variant effects including splicing and TAL1 mechanisms

Episode 276

January 30, 2026

276: AlphaGenome: 1-Mb multimodal deep model predicts regulatory variant effects including splicing and TAL1 mechanisms

Avsec et al., Advancing regulatory variant effect prediction with AlphaGenome. Nature 649, 1206–1218 ( - AlphaGenome, a 1 Mb DNA deep‑learning model, predicts base‑pair‑resolution...

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00:19:40

275: MIPseq/WES of 11,555 CHD probands implicates 60 dominant genes with NOTCH1 cysteine‑altering and transmitted MYH6 missense variants

Episode 275

January 30, 2026

275: MIPseq/WES of 11,555 CHD probands implicates 60 dominant genes with NOTCH1 cysteine‑altering and transmitted MYH6 missense variants

Sierant MC et al., PNAS - MIPseq and exome sequencing of 11,555 human congenital heart disease probands implicate 60 dominant CHD genes, with NOTCH1...

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00:19:55

274: RPE-specific MCT2 gene delivery preserves cones and vision in rat and mouse models of retinitis pigmentosa

Episode 274

January 29, 2026

274: RPE-specific MCT2 gene delivery preserves cones and vision in rat and mouse models of retinitis pigmentosa

Chandler LC et al., PNAS - AAV-mediated RPE expression of MCT2 in rat and mouse retinitis pigmentosa models increases RPE lactate uptake and prolongs...

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00:22:16

273: CTVT-A acquires 15-Mb N-HT1 dicentric nuclear element via horizontal transfer

Episode 273

January 28, 2026

273: CTVT-A acquires 15-Mb N-HT1 dicentric nuclear element via horizontal transfer

Gori K et al., PNAS - In canine transmissible venereal tumor (CTVT), deep sequencing and cytogenetics identify a 15‑Mb horizontally transferred nuclear element (N-HT1)...

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00:18:32

272: ADSL A429V reduces purine biosynthesis in brain and alters female mouse water-seeking behavior

Episode 272

January 27, 2026

272: ADSL A429V reduces purine biosynthesis in brain and alters female mouse water-seeking behavior

Ju X-C et al., PNAS - Human-specific ADSL A429V substitution and a common regulatory haplotype reduce ADSL activity and raise purine substrates in the...

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00:22:11