Genetics, Gene Therapy & Genetic Disease
A novel canis lupus familiaris reference genome improves variant resolution for use in breed-specific GWASThis paper describes the economical optimization of DNA extraction, short and long read sequencing, and bioinformatic assembly, which in turn improves mapping and variant resolution of short-read sequenced, same-breed dogs for association studies. This methodology is applicable for any investigators planning a genome-wide association study.
Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse modelsThis study used mice heterozygous for Tp53 mutations with different genetic backgrounds to investigate the genetic or stochastic factors that modify the penetrance of tumor formation by Tp53 mutation.
Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophyWe describe drug treatment paradigms that allow investigation of cellular and molecular pathogenesis at different stages of spinal muscular atrophy in a mouse model.
Inhibition of a transcriptional repressor rescues hearing in a splicing factor–deficient mouseThe vital role of the splicing factor SRRM4 in vestibular and inner hair cells of the ear is inactivation of the gene repressor REST; however, in outer hair cells, SRRM4 is dispensable for REST inactivation, which SRRM3 accomplishes independently.
Incipient sympatric speciation in wild barley caused by geological-edaphic divergenceSympatric speciation is still contentious but here based on genome-wide analysis; we show incipient sympatric speciation of an emerging new wild barley species from Hordeum spontaneum, the progenitor of all cultivated barleys at “Evolution Plateau” (EP), Upper Galilee, Israel.
multicrispr: gRNA design for prime editing and parallel targeting of thousands of targetsA bioinformatics R package for a fast and generic guideRNA design, optimized for large-scale perturbation assays.
Biochemical and functional characterization of a meiosis-specific Pch2/ORC AAA+ assemblyThe AAA+ protein Pch2 forms a biochemical complex with Orc1/ORC to suppress DNA break formation in the meiotic G2/prophase.
DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesisIn intestinal epithelial cells (IECs), DDX5 promotes the expression of immune response genes and oncogenes posttranscriptionally and is a novel therapeutic target for treating colitis and intestinal cancers.
Small molecule inhibitors and a kinase-dead expressing mouse model demonstrate that the kinase activity of Chk1 is essential for mouse embryos and cancer cellsThe study use small molecule inhibitors and a kinase-dead expressing mouse model to demonstrate that the kinase activity of Chk1 is essential for mouse embryos and cancer cells.
RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levelsThe work highlights the link between dysfunction of the RNA exosome, ribosome biogenesis, p53-dependent signalling, and apoptosis. Pontocerebellar hypoplasia caused by mutations of the exosome subunits could be classified as a ribosomopathy.