Base by Base

Massilania D et al., PNAS - We summarize a PNAS study reporting a ~37× genome from a ~110,000-year-old male Neandertal (Denisova 17) from Denisova Cave. The genome shows D17 is closely related to an earlier Denisova Neandertal (D5), both carry Denisovan introgressed segments, and Neandertal groups displayed high regional differentiation and small, isolated populations in the Altai. Key terms: Nean...

Law C-T et al., Cell Genomics - Law and Burns introduce TiMEstamp, a comparative-genomics pipeline that dates LINE-1 insertions from multiple sequence alignments and discovers hundreds of LINE-1 chimeric insertions fused to diverse RNAs across mammalian evolution. Key terms: LINE-1, TiMEstamp, chimeric insertions, retrotransposition, comparative genomics. Study Highlights: The authors developed Ti...

Jiang P et al., Cell Genomics - This episode reviews a Cell Genomics study that uses ssDNA '2-end' and novel '4-end' sequencing to profile native 5′ and 3′ termini of plasma cfDNA. The work identifies PREM/POEM markers, links 3′ ends to methylation, and shows improved HCC detection. Key terms: cfDNA fragmentomics, 3' end motifs, 4-end sequencing, hepatocellular carcinoma, DNASE1L3. Study Highlight...

Jiang P et al., Cell Genomics - This episode reviews a Cell Genomics study that uses ssDNA '2-end' and novel '4-end' sequencing to profile native 5′ and 3′ termini of plasma cfDNA. The work identifies PREM/POEM markers, links 3′ ends to methylation, and shows improved HCC detection. Key terms: cfDNA fragmentomics, 3' end motifs, 4-end sequencing, hepatocellular carcinoma, DNASE1L3. Study Highlight...

Liao Y et al., PNAS - Human dermal fibroblasts from young and old donors were embedded in 3D collagen and exposed to mechanical tension and TGF-β. Combining bulk RNA‑seq, ATAC‑seq, imaging, and perturbations, the study shows that matrix tension amplifies TGF‑β responses in young but not aged cells and identifies AP‑1 as a central chromatin-associated regulator required for fibroblast activation. K...

Tan et al et al., The American Journal of Human Genetics - This report identifies bi-allelic NDUFA5 variants in four individuals from three families causing an isolated mitochondrial complex I deficiency with variable multisystem features. The study combines genomic, transcriptomic, proteomic, biochemical, structural modeling, and zebrafish functional data to support pathogenicity. Key terms: NDUF...

Chaldebas M et al., The American Journal of Human Genetics - Chaldebas et al. present 5ULTRA, a computational pipeline that integrates uORF databases, Kozak-motif features, splicing prediction, and a random-forest score to detect and prioritize 5′ UTR variants predicted to alter protein translation. The score correlates with proteomic and MPRA measures and is applied to population, somatic, GWAS,...

Mualim KS et al., Proceedings of the National Academy of Sciences - This study develops spatiotemporal population-genetic models calibrated with genomic data to predict how habitat loss and fragmentation drive changes in nucleotide diversity (π). The authors translate IUCN, Living Planet Index, and GBF indicators into estimates of current and future genetic diversity loss across thousands of speci...

Zhou A et al., Human Genetics and Genomics Advances - Comparing LD‑pruning, COJO, SuSiE and PCA in haptoglobin (HP) cis‑region data, the study finds including non‑lead variants substantially increases variance explained (R2) and MR precision. Key terms: haptoglobin, cis-Mendelian randomization, LD-pruning, SuSiE, COJO. Study Highlights: The study analyzed circulating haptoglobin (HP) using Fenland...

Lambton J et al., The American Journal of Human Genetics - Bi-allelic ATG12 variants disrupt ATG12‑ATG5 conjugation and LC3 lipidation, impairing autophagy in patient cells and model systems and causing cerebellar vermis hypoplasia. Key terms: ATG12, autophagy, neurodevelopmental disorder, zebrafish, LC3 lipidation. Study Highlights: The study characterized six affected individuals with bi-allelic...

Strand LG et al., Proc. Natl. Acad. Sci. U.S.A - In C. elegans germline, the deubiquitinase DUO-1 is required for assembly and active maintenance of the synaptonemal complex and REC-8 cohesin, preventing RAD-51 accumulation and ensuring diakinesis compaction. Key terms: DUO-1, Caenorhabditis elegans, synaptonemal complex, REC-8, auxin-inducible degron. Study Highlights: Using C. elegans germline a...

Lawrence et al., The American Journal of Human Genetics - Using a cis-principal-component (pcQTL) approach in human GTEx tissues, the authors uncover novel multi-gene regulatory variants and 33% more GWAS colocalizations than single-gene eQTLs. Key terms: pcQTL, allelic proxitropy, GTEx, colocalization, HOXB. Study Highlights: The study analyzes 13 human GTEx tissues and identifies clusters of co-...

Farnung J et al., Nature - Cryo-EM and biochemical reconstitution reveal how the ZSWIM8–CUL3 E3 ligase recognizes human AGO2–miRNA–trigger complexes to polyubiquitylate AGO and drive targeted microRNA degradation. Key terms: ZSWIM8, AGO2, target-directed miRNA degradation, cryo-EM structure, E3 ubiquitin ligase. Study Highlights: Using purified human proteins and cellular assays, the authors combi...

Norgren J et al., JAMA Network Open - Population-based SNAC-K study finds higher meat consumption associated with slower cognitive decline and lower dementia risk in APOE ε3/ε4 and ε4/ε4 older adults. Key terms: APOE4, meat consumption, dementia, episodic memory, SNAC-K. Study Highlights: Using the Swedish National Study on Aging and Care–Kungsholmen (SNAC-K) cohort of older adults and repeated va...

Johnson MB et al., The American Journal of Human Genetics - Bi-allelic variants in snRNAs RNU6ATAC and RNU4ATAC cause infancy-onset autoimmune diabetes in humans, with RNA-seq showing U12 intron retention and impaired B cell development. Key terms: RNU6ATAC, RNU4ATAC, minor spliceosome, U12 intron retention, autoimmune diabetes. Study Highlights: In human infants with early-onset diabetes and immu...

Koga T et al., Nature Astronomy - Ryugu asteroid samples analyzed by HPLC/ESI-HRMS reveal all five canonical nucleobases (adenine, guanine, cytosine, thymine, uracil) and distribution linked to ammonia. Key terms: Ryugu, nucleobases, adenine, HPLC/ESI-HRMS, purine-to-pyrimidine ratio. Study Highlights: The team analysed Ryugu aggregate samples A0480 and C0370 and the Orgueil meteorite using water...

Amour C et al., Human Genetics and Genomics Advances, Journal Pre-proof - Sex-stratified cQTL mapping in Tanzanian and Dutch adults identifies sex-specific regulators such as TOX-linked IFN-γ in males and EGFR-linked IL-10 in females, revealing multiple genome-wide cQTLs. Key terms: TOX, EGFR, cytokine QTL, sex-stratified GWAS, Tanzania-Netherlands. Study Highlights: The study analyzed cytokine pr...

Fortuno C et al., Human Genetics and Genomics Advances - TP53 germline variant analysis using functional assays finds reduced-penetrance variants have intermediate activity, higher frequency, later onset, and 106 predicted candidates. Key terms: TP53, reduced penetrance, Li-Fraumeni syndrome, functional assays, variant interpretation. Study Highlights: Using ClinVar curation and comparison to beni...

Mendez R et al., Human Genetics and Genomics Advances, Journal Pre-proof - Biallelic RNU6ATAC variants disrupt the U6atac minor spliceosomal snRNA, causing transcriptome-wide minor intron retention and short stature with variable multisystem manifestations. Key terms: RNU6ATAC, U6atac, minor spliceosome, minor intron retention, whole-genome sequencing. Study Highlights: This study analyzed three u...

Saferali A et al., Human Genetics and Genomics Advances - Overlap between COPD genetic association results and transcriptional quantitative trait loci. RNA-seq in human lung (LTRC) and blood (COPDGene) reveals COPD-associated variants colocalize with splicing QTLs, implicating FBXO38 cryptic exon NMD and BTC exon4 isoform shifts. Key terms: COPD, sQTL, FBXO38, Betacellulin (BTC), long-read RNA-seq...

Pimplaskar A et al., The American Journal of Human Genetics - In UCLA ATLAS EHR-linked biobank analyses, random forest-derived enrollment probabilities and inverse-probability weighting increased replication of known GWAS variants and altered PGS associations. Key terms: inclusion bias, UCLA ATLAS, inverse-probability weighting, random forest, polygenic scores. Study Highlights: Using the UCLA ATL...

Mathur Y et al., Nature - Clinical surveillance in Bangladesh shows Vibrio cholerae acquired PLE11 encoding Rta that restricts ICP1 tail assembly, driving a selective sweep of phage-resistant strains. Key terms: Vibrio cholerae, ICP1, PLE11, Rta, phage coevolution. Study Highlights: This study analysed clinical Vibrio cholerae and ICP1 isolates from stool in Bangladesh using genomic surveillance,...

Rockowitz S et al., Human Genetics and Genomics Advances - Boston Children's Hospital used VS-NN, HPO NLP, and DRAGEN reprocessing in a proactive genomic reanalysis to identify candidate diagnoses in 2% of pediatric ES/GS cases. Key terms: genomic reanalysis, proactive reanalysis, VS-NN, HPO NLP, rare disease diagnostics. Study Highlights: The study deployed a centralized Proactive Genomic Reanaly...

Cromer SJ et al., The American Journal of Human Genetics - This paper reviews polygenic risk scores (PRS) and social determinants of health (SDoH) and outlines best practices for integrating PRS and SDoH across diverse populations to improve prediction and equity. Key terms: polygenic risk scores, social determinants of health, PRS transferability, data harmonization, type 2 diabetes. Study Highli...

Wong BHH et al., Proc. Natl. Acad. Sci. U.S.A - Mouse and human studies show the LPC transporter Mfsd2a enables plasma-derived LPC uptake into keratinocytes, preserving linoleate-rich phosphatidylcholine pools and promoting epidermal differentiation. Key terms: Mfsd2a, lysophosphatidylcholine, keratinocyte differentiation, linoleic acid, lipidomics. Study Highlights: Using epidermis-specific (2aEp...