Base by Base

Matar O et al., Trends in Genetics - Animal origins: looping back in time Music: Enjoy the music based on this article at the end of the episode. Article title: Animal origins: looping back in time First author: Matar O Journal: Trends in Genetics DOI: 10.1016/j.tig.2025.06.013 Reference: Matar O., Marlétaz F.. Animal origins: looping back in time. Trends in Genetics, 41, 849-850. (2025). https://...

Robles-Remacho A et al., Trends in Genetics - A concise review of emerging methods to map microRNA (miRNA) expression in tissues with spatial context, covering imaging and sequencing approaches, technical barriers, bioinformatics needs, and clinical implications. Key terms: spatial miRNomics, microRNA, spatial transcriptomics, in situ polyadenylation, Patho-DBiT. Study Highlights: Spatial miRNA pr...

Huang X et al., Trends in Genetics - A concise review of methodological advances for identifying introgressed loci across genomes. The article surveys summary statistics, probabilistic modeling, and supervised learning approaches, their applications beyond humans, and the main challenges for robust inference and software implementation. Key terms: introgression, genomic-landscapes, probabilistic-m...

Wen L et al., Trends in Genetics - This review surveys the integration of single-molecule long-read sequencing (SMS) with single-cell genomics, epigenomics and transcriptomics, describing platforms, methods and the new biological 'dark matter' now accessible at single-cell resolution. Key terms: single-cell sequencing, long-read sequencing, alternative splicing, structural variation, transposable...

Bleidorn C et al., Trends in Genetics - This episode examines a Trends in Genetics review arguing that short-read shotgun sequencing and genome skimming remain powerful, cost-effective tools for biodiversity research. The authors highlight applications from species identification and biomass estimation to phylogenomics and museum-based genomics, and discuss how short reads complement long-read ini...

Aston AN et al., Trends in Genetics - This opinion article reviews how short sequence interruptions within expanded tandem repeats alter somatic instability and clinical outcomes across multiple repeat expansion diseases, and proposes synthesis-dependent microhomology-mediated end joining (SD-MMEJ) as a unifying mechanism to explain the gain, loss, and complexity of interruptions. Key terms: repea...

Villalba A et al., Trends in Genetics - A concise exploration of how synthetic DNA could enable engineered haploid gametes, why that possibility intensifies the philosophical non-identity problem, and what this means for reproductive autonomy, disease prevention, and concerns about eugenics in future reproduction. Key terms: synthetic gametes, non-identity problem, reproductive ethics, synDNA, eug...

Cheng Y et al., Cell - This episode summarizes a technical report focused on ZFKLO[N and its relationships with ZUF and TKZLO[N systems as presented in the provided PDF. The document documents repeated observations, registry annotations (IZO[WZ), and structural motifs (tz�o~km�t{z) across samples. We highlight core methods, recurring patterns, and implications for standardized reporting. Key terms...

Erkut E et al., The American Journal of Human Genetics - This episode examines an international cohort of 18 individuals with de novo or loss-of-function variants in EIF3A or EIF3B who present with congenital heart defects, craniofacial differences, and mild neurodevelopmental features, and reviews zebrafish CRISPR models that recapitulate key aspects of the human phenotype. Key terms: EIF3A, EIF3...

Temple SD et al., The American Journal of Human Genetics - Temple and Browning model correlations of identity-by-descent (IBD) rates to derive analytical and simulation-based genome-wide significance thresholds for selection scans, apply these to TOPMed and UK Biobank cohorts, and show many signals cluster near structural-variant hotspots. Key terms: identity-by-descent, selection scans, multiple...

Wilson EPW et al., The American Journal of Human Genetics - This episode covers a skeletal muscle eQTL meta-analysis of 1,002 individuals that discovered 18,818 conditionally distinct regulatory signals across 12,283 genes and integrated these with GWAS to nominate candidate genes for muscular and cardiometabolic traits, including functional validation of an INHBB regulatory variant. Key terms: eQ...

Alheraky A et al., Clinical Chemistry - This episode reviews a validation study of a single-well multiplex ddPCR assay that quantifies TPSAB1 α- and β-tryptase copy numbers to diagnose hereditary alpha tryptasemia (HαT) and defines an optimal basal serum tryptase (BST) cutoff for clinical screening. Key terms: hereditary alpha tryptasemia, ddPCR, TPSAB1, basal serum tryptase, copy number variation...

van der Leest P et al., Clinical Chemistry - An interlaboratory external quality assessment across 16 laboratories in the Dutch COIN consortium evaluated how diverse (pre)analytical workflows and analytical platforms affect detection and genotyping of ctDNA mutations in plasma. Key terms: ctDNA, liquid biopsy, external quality assessment, NGS, preanalytical standardization. Study Highlights: Six o...

Guyon L et al., Nature Communications - Forward-time simulations and coalescent inference show that variance in reproductive success among patrilineal descent groups combined with lineal fission can produce the observed post‑Neolithic decline in male effective population size (Y chromosome) without requiring large-scale intermale violence. Key terms: patrilineality, Y-chromosome bottleneck, popula...

Kivisild T et al., Hum Genet (2017) 136:529–546 - Review of how high-throughput sequencing of ancient human remains has enabled genome-scale study of male-specific Y chromosome variation, the methodological challenges of working with ancient Y data, and examples of regional continuity and turnover in Y haplogroups across Eurasia and the Americas. Key terms: ancient DNA, Y chromosome, haplogroups,...

Sanoguera-Miralles L et al., Clinical Chemistry - This episode examines a minigene-based functional study of 52 CHEK2 splice-site variants from the BRIDGES project, reporting widespread splice disruption, characterization of 89 transcripts, and an ACMG/AMP-informed tentative clinical classification. Key terms: CHEK2, splicing, minigene assay, variant classification, breast cancer. Study Highlights...

Ying Y et al., Clinical Chemistry 71:4 (2025) 510–519 - This episode reviews a Clinical Chemistry study that developed an improved one-step ultra-long-range PCR with PCR suppression primers and PacBio SMRT long-read sequencing to obtain 26.1 kb full-length ABO haplotypes from the 5′ UTR to the 3′ UTR, enabling comprehensive allele annotation and resolution of complex ABO variants. Key terms: ABO,...

Chan HT et al et al., Clinical Chemistry - This study evaluates an automated, decentralized cfDNA NGS workflow (Oncomine Precision Assay GX with the Genexus system) in 298 patients with advanced solid tumors. The assay achieved 99% sequencing success, detected mut-ctDNA in about half of patients, identified actionable or resistance alterations in 18% of patients, and showed 72% concordance with ma...

Marín F et al., Clinical Chemistry - This episode examines a validation study of a highly sensitive NGS-based microsatellite instability (hs-MSI) assay for diagnosing constitutional mismatch repair deficiency (CMMRD). The assay was tested on blinded blood cohorts and CMMRD-associated tumors, compared with a low-pass whole-genome LOGIC/MMRDness score, and evaluated for gene-specific MSI indel patte...

Poszewiecka B et al., BMC Genomics (2022) 23:616 - This study presents an improved algorithm to compute the UBCS statistic and uses it to re-estimate the timing of the ancestral fusion that formed human chromosome 2, comparing human and Great Ape genomes. Key terms: human chromosome 2, chromosomal fusion, biased gene conversion, UBCS statistic, Great Apes evolution. Study Highlights: The authors d...

Skourtanioti E et al., Cell - This episode summarizes a population‑genomic analysis that models genetic outliers in ancient Eurasian samples, using PCA and admixture modeling to test source combinations and estimate ancestry proportions among Caucasus, steppe, and Central Asian groups. Key terms: ancient DNA, admixture, Caucasus, Sarmatian, population genomics. Study Highlights: The authors analyz...

Richardson M et al., The American Journal of Human Genetics - An international HBOP Variant Curation Expert Panel developed PALB2-specific specifications of the 2015 ACMG/AMP variant-interpretation guidelines by tailoring, limiting, or removing existing codes and tested them on 39 pilot variants to improve ClinVar concordance and harmonize classification. Key terms: PALB2, ACMG/AMP, variant curati...

Rivolta C et al., The American Journal of Human Genetics - RetiGene is an expert‑curated, openly accessible atlas integrating variant data, bulk and single‑cell RNA‑seq, and functional annotations for genes linked to inherited retinal diseases to aid diagnosis and research. Key terms: RetiGene, inherited retinal diseases, gene atlas, single-cell RNA-seq, diagnostic genetics. Study Highlights: The...

Axakova A et al., The American Journal of Human Genetics - Axakova et al. produced comprehensive missense variant-effect maps for human SOD1 by assaying enzymatic activity in yeast and protein abundance in human HEK293T cells for ~86% of possible missense substitutions. The study links map patterns to sequence-structure-function features, uses kernel-density calibration to provide LLRp evidence fo...

Timonina V et al., The American Journal of Human Genetics - MosCoverY is a coverage-based method that estimates mosaic loss of the Y chromosome (mLOY) from exome or whole-genome sequencing by normalizing single-copy MSY exon coverage to matched autosomal exons. The method was validated in 212,062 UK Biobank men and applied to SHCS and TCGA datasets. Key terms: mosaic loss of Y, exome sequencing, w...