Base by Base

Herpe L et al., Proc. Natl. Acad. Sci. U.S.A - CRISPR knockout of Drosophila mtG3PDH (GPO1) reduces ATP production by ~60% and O2 consumption by ~33%, lowering mitochondrial efficiency and ROS emission. Key terms: mtG3PDH, GPO1, Drosophila melanogaster, mitochondrial efficiency, reactive oxygen species. Study Highlights: Using CRISPR/Cas9-generated GPO1 mutant Drosophila and isolated thoracic mito...

Korpela K et al., Gut Microbes - Review finds maternal fecal microbiota transplantation and targeted probiotics can restore Bifidobacterium and Bacteroides after C‑section or intrapartum antibiotics, with breastfeeding aiding recovery. Key terms: maternal fecal microbiota transplantation, C-section, Bifidobacterium, vaginal seeding, probiotics. Study Highlights: This review focuses on term infants...

Li Z et al., Human Genetics and Genomics Advances - LASI-DAD 30× whole-genome sequencing of 2,680 Indian participants produced a 69.5M-variant LD panel that improves genotype imputation accuracy and PRS performance for Indian populations. Key terms: LASI-DAD, linkage disequilibrium, genotype imputation, whole-genome sequencing, polygenic risk scores. Study Highlights: Using 30× WGS of 2,680 LASI-D...

Shi J et al., The EMBO Journal, doi:10.1038/s44318-025-00687-8 - PANDORA-seq profiling of mouse and human sperm heads identifies a conserved rsRNA length shift with age and a tsRNA/rsRNA 'aging cliff' that reprograms embryonic transcripts. Key terms: sperm sncRNA, rsRNA length shift, PANDORA-seq, aging cliff, tRNA-derived small RNA. Study Highlights: Using PANDORA-seq on C57BL/6J mouse sperm (inta...

Saxton DS et al., Nature, doi:10.1038/s41586-026-10207-1 - In E. coli, the membrane-bound nuclease SNIPE directly cleaves incoming phage λ DNA during genome injection, blocking infection via ManYZ and tape-measure protein interactions. Key terms: SNIPE, GIY-YIG nuclease, lambda phage, ManYZ, tape measure protein. Study Highlights: In Escherichia coli, the membrane-anchored protein SNIPE was shown...

Moye AR et al., The American Journal of Human Genetics - Biallelic loss-of-function variants in SAXO6, a microtubule inner protein of photoreceptor cilia, cause late-onset retinal dystrophy by destabilizing axonemal microtubules. Key terms: SAXO6, microtubule inner protein, photoreceptor cilia, retinal dystrophy, iU-ExM. Study Highlights: The study analyzed human patients with late-onset recessive...

Siraj L et al., Nature, doi:10.1038/s41586-026-10121-6 - Using MPRA in five human cell types, the authors assayed 221,412 fine-mapped variants and identified 13,121 trait-associated regulatory variants (TARVs), mapping mechanisms at single-nucleotide resolution. Key terms: massively parallel reporter assay, trait-associated regulatory variants, saturation mutagenesis, transcription factor motifs,...

Baldwin-Brown JG et al., Annual Review of Ecology and Systematics - Bayesian analysis of 76,445 Utah Population Database pedigrees identifies a patrilineal Y‑chromosome lineage producing a 2:1 male bias, consistent with segregation distortion. Key terms: segregation distortion, Y chromosome, sex ratio, Utah Population Database, Bayesian pedigree analysis. Episode title: Patrilineal Y‑chromosome dr...

Bleidorn C et al., Trends in Genetics, 42 (2026) 137-149. doi:10.1016/j.tig.2025.09.001 - This review shows how short-read shotgun sequencing and genome skimming recover organellar genomes, estimate genome size and repeat content, and enable scalable biodiversity monitoring. Key terms: short-read sequencing, genome skimming, metagenomics, museum genomics, phylogenomics. Study Highlights: The autho...

Ein Hommage-Dossier , das die wissenschaftliche Laufbahn von Prof. Brunhilde Wirth würdigt und Arbeiten zum alternativen Spleißen von SMN1/SMN2 hervorhebt. Im Fokus stehen Studien aus der molekularen Genetik und funktionelle Assays, die die Auswirkungen von Varianten bei SMA aufgeklärt haben. Studien-Highlights: Dieses Dossier beleuchtet jahrzehntelange Arbeit in der Humangenetik und zur spinalen...

The Last Exon Light: A Tribute Dossier Celebrating the Scientific Career of Prof. Dr. Brunhilde Wirth - Special tribute episode honoring Prof. Dr. Brunhilde Wirth and synthesizing recurring themes across her work on SMN1/SMN2 splicing, variant interpretation, and spinal muscular atrophy. Study Highlights: This special episode is based on a tribute dossier rather than a single new primary research...

Ferolito BR et al., Human Genetics and Genomics Advances, 7 (2026) 100556. doi:10.1016/j.xhgg.2025.100556 - Meta-analysis of MVP, UK Biobank and FinnGen with Mendelian randomization using eQTL/pQTL instruments implicates 6,447 genes and 69,669 causal gene-trait links. Key terms: Mendelian randomization, biobank meta-analysis, pQTL, drug target discovery, machine learning ranking. Study Highlights:...

Nyeo SS et al., Nature, doi:10.1038/s41586-025-10020-2 - Population-scale WGS reanalysis quantifies persistent EBV DNA and shows MHC class II–mediated antigen presentation predicts EBV DNAemia and links to autoimmune and respiratory disease. Key terms: Epstein–Barr virus, MHC class II, whole-genome sequencing, HLA, antigen presentation. Study Highlights: Using whole-genome sequencing from UK Bioba...

Perdigão C et al., EMBO Molecular Medicine, doi:10.1038/s44321-026-00389-6 - In mouse neurons, UFM1 loss or UFM1-R81C expression reduces protein translation, triggers ER stress and PERK activation, impairing dendrite and synapse development. Key terms: UFM1, UFMylation, ER stress, protein translation, Trazodone. Study Highlights: Using murine UFM1-deficient neurons generated by conditional knockou...

Lin S et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2026.01.015 - Bi-allelic FSD1L variants cause retinitis pigmentosa; FSD1L localizes to the photoreceptor axoneme and a deep intronic deletion abolishes retina-enriched exon 10b inclusion. Key terms: FSD1L, retinitis pigmentosa, photoreceptor axoneme, exon 10b, minigene assay. Study Highlights: In human and mo...

Serpieri V et al., The American Journal of Human Genetics, Corrected proof. doi:10.1016/j.ajhg.2026.01.014 - Bi-allelic FSD1L variants disrupt a microtubule-associated protein, causing hydrocephalus, corpus callosum defects and an L1 syndrome-like neurodevelopmental disorder in humans and models. Key terms: FSD1L, microtubules, ciliogenesis, hydrocephalus, iPSC neuronal differentiation. Study High...

Zhou S et al., Nature Communications, doi:10.1038/s41467-025-65448-x - snaR-A noncoding RNA interacts with U2 snRNP subunit SF3B2 and nuclear speckles, increasing intron retention and promoting proliferation in human cancer-relevant cells. Key terms: snaR-A, SF3B2, intron retention, nuclear speckles, RNA polymerase III. Study Highlights: Using human cell lines (HEK293T, A549, THP-1) and tumor chro...

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 bowel disease, suggesting targeted CFTR modulation as a potential IBD therapy. Key terms: CFTR, deltaF508, inflammatory bowel disease, exome sequencing, rare-variant burden test. Study Highlights: The authors...

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 RNA-seq, reshapes gene regulation and drives phenotypic evolution in mammals. Key terms: alternative splicing, exonization, long-read RNA-seq, microexons, comparative transcriptomics. Study Highlights: This review synthe...

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 Siamese transfer-learning model that achieves state-of-the-art pathogenicity prediction with MCC = 0.77. Key terms: IndeLLM, protein language models, in-frame indels, Siamese network, ESM2. Study Highlights: Using human protein se...

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 and causes recessive insulin-deficient diabetes in homozygotes. Key terms: INS R6C, preproinsulin translocation, iPSC-derived beta cells, monogenic diabetes, population genetics. Study Highlights: The study inte...

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 with cytoskeleton, endomembrane system and nucleus before mitochondrial acquisition around 2.2 Ga. Key terms: eukaryogenesis, Asgard archaea, mitochondrial endosymbiosis, gene duplication, molecular clock. Stud...

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...