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Oncogene amplification is a major driver of tumorigenesis; yet, the mechanisms generating amplification are only partially understood. New research reports on the identification of a new focal amplification pattern termed ‘seismic amplification’ that is hypothesized to originate from recombination between extrachromosomal DNA circles.
Seismic amplifications arise from several cycles of circular recombination of circular extrachromosomal DNA formed as a result of chromothripsis. The process provides a mechanism for oncogene amplification in a number of different human tumor types.
Polycomb proteins can regulate epigenetic transcriptional memory during cell differentiation. This memory operates in cis and is linked to the strength of activating inputs.
The language used in genetic and medical research to describe populations has a fraught history, and current practices must be sensitively considered when reporting on genetic cohorts and analyses.
How somatic and germline mutations interact in cancer remains largely unexplored. A study of 17,152 patients with cancer suggests that the relative contribution of pathogenic germline mutations is governed by lineage and penetrance.
A concerning trend in genetics is the common use of the term ‘trans-ethnic’ to describe analyses that combine or compare several ancestrally diverse populations. In this commentary, we discuss how this term is inaccurate and alienating. We propose that geneticists avoid using the term trans-ethnic entirely and that researchers across disciplines reach a new consensus about the best terms to use to describe the populations we study.
A study of 17,152 patients with cancer identified pathogenic germline variants in cancer predisposition genes. Although tumors showed biallelic inactivation for high-penetrance genes, this was not the case in most patients with pathogenic variants in low-penetrance genes, suggesting alternative routes to tumorigenesis.
Genome-wide association analysis of irritable bowel syndrome identifies genetic susceptibility loci and highlights shared pathways with mood and anxiety disorders.
A new study shows that re-expressing PKD genes early in the course of the disease can fully reverse polycystic kidney disease in mice. These results reveal an unexpected ability of the kidney to regenerate following genetic rescue of polycystin function.
The genomes of cells across human tissues are riddled by changes to their DNA1–3. Many of these mutations do not alter the properties of a cell, and are neutral passengers. However, a small proportion can change a cell’s fitness, and increase or decrease the progeny that originate from the mutated cell4. How many of these alterations under positive selection (drivers) exist in total is unknown. Whether the current list of drivers is almost complete, or whether large proportions of positively selected drivers in the human genome remain undetected is yet to be determined.
FastGWA-GLMM is a fast, scalable generalized linear mixed model method for genetic association testing for binary traits in large cohorts that is robust to variant frequency and case–control imbalance.
Synonymous passenger mutations are used to measure levels of positive selection in healthy blood and esophagus. This approach can quantify missing selection due to unidentified drivers.
SNP rs17713054 in the 3p21.31 COVID-19 risk locus is identified as a probable causative variant for disease association. Chromatin conformation and gene expression data indicate that LZTFL1 is impacted by rs17713054 in pulmonary epithelial cells.
Open Targets Genetics is a community resource that provides systematic fine mapping at human GWAS loci, enabling users to prioritize genes at disease-associated regions and assess their potential as drug targets.
Mutational signatures can shed light onto mechanisms of carcinogenesis and reveal the mutagenic impact of novel and established environmental risk factors. A new study examines the mutational spectra of esophageal squamous cell cancer together with exposure information in regions of high and low incidence of the disease, and demonstrates both the limitations and potential of mutational signature analyses.
