1-Methyl-1-nitrosourea (MNU) induced specific-locus mutations in mice in all spermatogenic stages except spermatozoa. After intraperitoneal injection of 70 mg/kg body weight of MNU a high yield of specific-locus mutations was observed in spermatids (21.8 x 10(-5) mutations per locus per gamete). The highest mutational yield was induced in differentiating spermatogonia. In 1594 offspring we observed 5 specific-locus mutants (44.8 x 10(-5) mutations per locus per gamete). In addition, 2 mosaics were recovered, which gave a combined mutation rate of 62.7 x 10(-5). In As spermatogonia the mutation rate was 3.9 x 10(-5). The same dose of 70 mg/kg of MNU induced dominant lethal mutations 5-48 days post treatment, mainly due to post-implantation loss in spermatids and spermatocytes. It is interesting to compare the induction pattern of mutations by MNU with methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and ethylnitrosourea (ENU). Based on the different spermatogenic response of the induction of specific-locus mutations we can characterize the 4 mutagens in the following way: EMS = MMS not equal to MNU not equal to ENU.
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http://dx.doi.org/10.1016/0027-5107(91)90201-x | DOI Listing |
Med
December 2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:
Background: Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications.
Methods: Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT.
Exp Mol Med
November 2024
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Human embryonic stem cells (hESCs) are naturally equipped to maintain genome integrity to minimize genetic mutations during early embryo development. However, genetic aberration risks and subsequent cellular changes in hESCs during in vitro culture pose a significant threat to stem cell therapy. While a few studies have reported specific somatic mutations and copy number variations (CNVs), the molecular mechanisms underlying the acquisition of 'culture-adapted phenotypes' by hESCs are largely unknown.
View Article and Find Full Text PDFGenes (Basel)
August 2024
Horticulture and Landscape Department, Heilongjiang Bayi Agriculture University, Daqing 163000, China.
Forensic Sci Int Genet
January 2025
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Portugal; Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal; Centro de Matemática da Universidade do Porto (CMUP), Portugal.
The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome.
View Article and Find Full Text PDFNeurobiol Dis
September 2024
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
Gain-of-function mutations in SCN8A cause developmental and epileptic encephalopathy (DEE), a disorder characterized by early-onset refractory seizures, deficits in motor and intellectual functions, and increased risk of sudden unexpected death in epilepsy. Altered activity of neurons in the corticohippocampal circuit has been reported in mouse models of DEE. We examined the effect of chronic seizures on gene expression in the hippocampus by single-nucleus RNA sequencing in mice expressing the patient mutation SCN8A-p.
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