Base by Base

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 newborn screening but produce a low-abundance, thermostable SMN protein that functionally rescues smn1-deficient zebrafish and averted therapy. Key terms: SMN1, spinal muscular atrophy, newborn screening, p. Arg288AlafsTer5...

Wirth B et al. (The American Journal of Human Genetics, 2026) — Zwei 4-bp-Deletionen in Exon 7 von SMN1 (p. Arg288AlafsTer5) entgehen dem Standard-PCR-Neugeborenenscreening, erzeugen jedoch ein SMN-Protein in sehr geringer Menge, das thermostabil ist, smn1-defiziente Zebrafische funktionell rettet und eine Therapie vermeiden half. Studien-Highlights: • Zwei klinisch gesunde Neugeborene wurden im P...

White R et al., F1000Research - Investigation of chimeric reads in MinION nanopore sequencing of short PCR amplicons, focusing on ligation-related artifacts, barcode tracing, and the prevalence of cross-gene chimeras in murine Ifna/Ifnb sequencing runs. Music: Enjoy the music based on this article at the end of the episode. Article title: Investigation of chimeric reads using the MinION First auth...

Sun C et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2524504123 - Using cryo-EM and mass spectrometry in rat cerebellum, α1- and α6-containing GABAA receptor assemblies (β‑α‑β‑α‑γ stoichiometry) and PZ-II-029 binding were defined. Key terms: GABAA receptor, cerebellum, α6 subunit, cryo-EM, pyrazoloquinolinone. Study Highlights: The study used rat cerebellum tissue and combined confocal immunofluo...

Granata J et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2527303123 - In mESCs and defined in vitro assays, EPOP and MTF2 stimulate PRC2 methyltransferase activity and promote de novo H3K27me3 deposition with GA- or GCN-rich DNA preference. Key terms: EPOP, MTF2, PRC2, H3K27me3, DNA-sequence specificity. Study Highlights: The study used mouse embryonic stem cells with an EED-rescue system and rec...

Larsen BB et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2529505123 - Deep mutational scanning of the Nipah virus fusion protein F using pseudoviruses maps ~8,500 single-residue effects, showing F is highly constrained and identifying antibody-escape mutations. Key terms: Nipah virus, fusion protein F, deep mutational scanning, pseudovirus, antibody neutralization. Study Highlights: Using nonrepl...

Berazategui MA et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2531377123 - ESBX (Tb927.3.1660) links RNA Pol I localization at the ESB to activation of the active BES and repression of inactive BESs in Trypanosoma brucei, supporting monoallelic VSG expression. Key terms: Trypanosoma brucei, ESBX (Tb927.3.1660), expression site body, variant surface glycoprotein, RNA polymerase I. Study Highlights...

Solomon CU et al., Nat Commun(2026). - Integrative analysis in human VSMCs identifies pleiotropic genes including FES that regulate vascular remodeling; pooled CRISPR and mouse knockout show FES loss increases MMPs, atherosclerosis and blood pressure. Key terms: FES, vascular smooth muscle cell, atherosclerosis, colocalization eQTL, CRISPR knockout screen. Study Highlights: The study used a large...

Ramírez Renta GM et al., The American Journal of Human Genetics, 113 (2026) 16-28. doi:10.1016/j.ajhg.2025.11.014 - GALS survey of >4,000 US respondents (GenPop and SPARK) shows confidence in genetic knowledge predicts Familiarity, Knowledge, and Skills, explaining ~25% of variance. Key terms: genetic literacy, confidence in knowledge, GALS, SPARK, science communication. Study Highlights: Using...

Liang Y et al., The American Journal of Human Genetics, 113 (2026) 276-290. doi:10.1016/j.ajhg.2025.12.014 - TWAS using genetically predicted expression exhibit polygenicity-driven inflation that increases with GWAS sample size and heritability; a gene-specific variance-control correction yields calibrated p values. Key terms: transcriptome-wide association study, TWAS, polygenicity, variance-cont...

Di Donato N et al., The American Journal of Human Genetics, 113 (2026) 324-341. doi:10.1016/j.ajhg.2025.12.007 - Analysis of 290 individuals with ACTB and ACTG1 variants defines eight distinct non-muscle actinopathies and links BWCFF-causing variants to altered actin polymerization dynamics. Key terms: ACTB, ACTG1, Baraitser-Winter, actin polymerization, genotype-phenotype. Study Highlights: The s...

Yan X et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2025.12.008 - In 569 TwinsUK subcutaneous adipose biopsies, twin models and GWAS identify SCD, FADS and 3p25.2 (PPARG) loci regulating fatty acid levels and conversions. Key terms: SCD, FADS1, PPARG, adipose-tissue, fatty-acids. Study Highlights: System and sample: 569 female TwinsUK subcutaneous adipose biop...

Guest O et al. - Position piece urging universities to resist uncritical adoption of AI technologies such as LLMs and chatbots because they undermine academic freedom, integrity, and pedagogical skills. Key terms: artificial intelligence, higher education, large language models, academic freedom, critical AI literacy. Study Highlights: System: the higher education sector and university classrooms;...

Rashid AI et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2025.12.012 - US antitrust shifts in human genetic technologies: FTC scrutiny of Illumina’s acquisition of Grail alters NGS market oversight and could affect spin-offs and startups. Key terms: Illumina, Grail, vertical mergers, FTC merger guidelines, non-compete rule. Study Highlights: This perspective ex...

Morsy H et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2025.12.015 - Exome sequencing identifies homozygous MDGA2 loss-of-function variants in nine individuals and functional neuronal assays show impaired MDGA2 trafficking with disrupted Nlgn1-dependent excitatory synapse regulation causing DEE. Key terms: MDGA2, developmental and epileptic encephalopathy, loss...

Avsec et al., Nature, doi:10.1038/s41586-025-10014-0 - AlphaGenome, a 1 Mb DNA deep‑learning model, predicts base‑pair‑resolution genome tracks (RNA‑seq, splicing, chromatin) and scores variant effects, achieving state‑of‑the‑art performance across modalities. Key terms: AlphaGenome, splicing, eQTL, chromatin-accessibility, 1Mb-sequence. Study Highlights: AlphaGenome is a unified sequence‑to‑funct...

Sierant MC et al., Proc. Natl. Acad. Sci. U.S.A. 2025.122:e2420343122 - MIPseq and exome sequencing of 11,555 human congenital heart disease probands implicate 60 dominant CHD genes, with NOTCH1 cysteine‑altering and transmitted MYH6 missense variants driving distinct defects. Key terms: congenital heart disease, NOTCH1, MYH6, MIPseq, de novo mutations. Study Highlights: We analyzed 11,555 human C...

PNAS - RPE-specific MCT2 gene delivery preserves cones and vision in retinitis pigmentosa models Music: Enjoy the music based on this article at the end of the episode. Article title: RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa Journal: PNAS DOI: 10.1073/pnas.2421978122 License: This episode is based on an open-access article published under the Creative C...

Gori K et al., Proc. Natl. Acad. Sci. U.S.A. 2025.122:e2424634122 - In canine transmissible venereal tumor (CTVT), deep sequencing and cytogenetics identify a 15‑Mb horizontally transferred nuclear element (N-HT1) acquired ~2,000 years ago that is transcriptionally active. Key terms: CTVT, horizontal gene transfer, N-HT1, PacBio long-read sequencing, centromeric fusion. Study Highlights: The autho...

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 raise purine substrates in the brain, altering mouse behavior. Key terms: adenylosuccinate lyase, A429V, purine biosynthesis, succinyladenosine, human evolution. Study Highlights: Model: mice humanized for ADSL carrying the modern-hum...

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 PGI associations with years of education increased from 1946–1970 and were strongest in advantaged socioeconomic backgrounds. Key terms: educational attainment, polygenic index, gene-environment interaction, British birth cohorts, socioeconomic sta...

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 negatively supercoiled DNA faster than PICH loops. Key terms: topoisomerase IIIα, TRR complex, DNA supercoiling, optical tweezers, ultrafine anaphase bridges. Study Highlights: Using torsionally constrained end-c...

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 to excise mispairs independent of Exo1 and Rad27. Key terms: Mlh1-Pms1, mismatch repair, single-strand gaps, Exo1, APOBEC3A. Study Highlights: We reconstituted Saccharomyces cerevisiae mismatch repair wi...

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 the super-relaxed state and increases actin attachment and contractile force. Key terms: β-cardiac myosin, M493I, super-relaxed state, actin attachment, optical trap. Study Highlights: System: recombinant human β-cardiac heavy...

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 base-pair opening modes: single-base microsecond openings and multi-base millisecond soliton-like loops. Key terms: hydrogen exchange, DNA dynamics, base pair opening, soliton, H-T exchange. Study Highlights: Systems studied include long polynucleotides...