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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

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., Proc. Natl. Acad. Sci. U.S.A. 2025.122:e2508540122 - Human-specific ADSL A429V substitution and a common regulatory haplotype reduce ADSL activity and...

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00:22:11

271: Rising EA PGI prediction of educational attainment across 1946–1970 British birth cohorts and socioeconomic interaction

Episode 271

January 25, 2026

271: Rising EA PGI prediction of educational attainment across 1946–1970 British birth cohorts and socioeconomic interaction

Morris TT et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2516460123 - EA and cognition polygenic indexes (PGIs) in three British birth cohorts show EA...

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00:19:56

270: Human Topoisomerase IIIα–RMI1–RMI2 (TRR) processively relaxes negatively supercoiled DNA measured by optical tweezers

Episode 270

January 25, 2026

270: Human Topoisomerase IIIα–RMI1–RMI2 (TRR) processively relaxes negatively supercoiled DNA measured by optical tweezers

Spakmana D et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2406949123 - Optical tweezers and fluorescence imaging show human Topoisomerase IIIα–RMI1–RMI2 (TRR) processively relaxes highly...

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00:22:04

269: Mlh1–Pms1 endonuclease creates single-strand gaps to excise mispairs in S. cerevisiae MMR

Episode 269

January 24, 2026

269: Mlh1–Pms1 endonuclease creates single-strand gaps to excise mispairs in S. cerevisiae MMR

Palacio T et al., Proc. Natl. Acad. Sci. U.S.A. 2025.122:e2528670122 - Reconstituted Saccharomyces cerevisiae mismatch repair shows the Mlh1–Pms1 endonuclease directly generates single-strand gaps...

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00:20:50

268: M493I in human β-cardiac myosin: SRX disruption, slow ADP release, and enhanced actin attachment

Episode 268

January 23, 2026

268: M493I in human β-cardiac myosin: SRX disruption, slow ADP release, and enhanced actin attachment

Cail RC et al., Proc. Natl. Acad. Sci. U.S.A. 2025.122:e2521561122 - Recombinant human β-cardiac myosin M493I studied by optical trapping and stopped-flow kinetics disrupts...

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00:22:09

267: DNA base-pair opening modes and soliton-like loops revealed by hydrogen exchange

Episode 267

January 22, 2026

267: DNA base-pair opening modes and soliton-like loops revealed by hydrogen exchange

Englander SW et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2520855122 - Hydrogen exchange (H-T and NMR H-H) on DNA and RNA reveals two distinct...

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00:21:24