We have studied the meiotic non-Mendelian segregation (NMS) pattern of seven large heterologous combinations located in the b2 ascospore gene of Ascobolus. The NMS patterns of these aberration heterozygotes widely differ from each other and from those of point mutations located in the same genetic region. They give lower gene conversion frequencies than point mutations, no postmeiotic segregations (PMS), and either parity or disparity that favors the wild type allele. Two related deletions, G234 and G40, were studied for their effects on the conversion behavior of closely linked point mutations. We found that, when heterozygous, the deletions impose their own NMS pattern onto close mutations. These effects occur on both sides of the heterologies. The effects upon PMS and disparity of linked point mutations gradually disappear as point mutations become more distant. The effects on NMS frequencies and on aberrant 4:4 are polar. They persist for all mutations located downstream from the high conversion end of the gene. This last effect can reflect a blockage of symmetric hDNA formation by large heterologies, whereas the epistasis of the NMS pattern of large heterologies over that of closely linked point mutations suggests that large heterologies and point mutations undergo conversion by means of distinct pathways.
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http://dx.doi.org/10.1093/genetics/116.1.45 | DOI Listing |
JTO Clin Res Rep
February 2025
Department of Medicine, Division of Oncology, Stanford University, Stanford, California.
Introduction: Although tyrosine kinase inhibitors (TKIs) are effective against NSCLC harboring sensitizing gene mutations, acquired resistance is inevitable. Preclinical studies suggest that combining EGFR TKI and monoclonal antibody therapies may have activity in mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with mutated NSCLC.
View Article and Find Full Text PDFStroke
January 2025
Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (M.F., S.B., S.M., K.W., M.E., A.M., U.D., C.S.).
Background: Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory.
View Article and Find Full Text PDFAnim Sci J
January 2025
Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Heat stress negatively affects the reproductive function of in animals and humans. Although a relationship between heat and oxidative stress has been suggested, the underlying mechanism has not been sufficiently examined in reproduction-related cells. Therefore, we aimed to investigate whether heat stress induces oxidative stress using a variety of reproduction-related cells including bovine placental and cumulus-granulosa cells, human cell lines derived from cervical and endometrial cancers, and fibroblasts derived from endometrium.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Background: Understanding the sequential progression of cognitive decline in autosomal dominant Alzheimer's disease (ADAD) in the Latino population is crucial for enhancing early identification for targeted interventions. Given the tablet-based administration and increasing frequency of use in epidemiological research, validating this progression within the NIH Toolbox cognitive battery (NIHTB-CB) is important.
Objective: The first aim was to utilize an innovative Event-Based Modeling (EBM) analytic approach to estimate the sequence of cognitive declines in persons at risk for ADAD enriched for being of Latino origin.
Cell Mol Biol Lett
January 2025
University Cote d'Azur, Inserm, C3M, Nice, France.
Vacuolization of hematopoietic precursors cells is a common future of several otherwise non-related clinical settings such as VEXAS, Chediak-Higashi syndrome and Danon disease. Although these disorders have a priori nothing to do with one other from a clinical point of view, all share abnormal vacuolization in different cell types including cells of the erythroid/myeloid lineage that is likely the consequence of moderate to drastic dysfunctions in the ubiquitin proteasome system and/or the endo-lysosomal pathway. Indeed, the genes affected in these three diseases UBA1, LYST or LAMP2 are known to be direct or indirect regulators of lysosome trafficking and function and/or of different modes of autophagy.
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