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Sequence comparison analysis has been carried out for 31 imprinted mouse genes and a set of 150 control genes. The imprinted genes were found to be associated with significantly reduced numbers of short interspersed transposable elements (SINEs), in particular SINE Alu repeats. This is similar to recent analyses of human imprinted genes and supports the suggestion that there is either active selection against SINE elements in imprinted regions or a reduced rate of insertion of these elements. The reduction in numbers of SINEs was more consistent in paternally expressed genes, whereas for maternally expressed genes significantly reduced numbers of SINE-B2 elements were coupled with increased numbers of SINE-B4 and SINE-ID elements. Paternally expressed genes were also found to be associated with a lower GC content. Discriminant analysis revealed that the two sub-groups of imprinted genes can be cleanly separated from each other on the basis of their genomic sequence characteristics and that they tend to localize to different genomic compartments. The differences between the sequence characteristics of imprinted and control genes have also enabled us to develop a discriminant function that can be used in a genome-wide screen to identify candidate imprinted genes.
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http://dx.doi.org/10.1007/s00335-002-3038-x | DOI Listing |
J Assist Reprod Genet
September 2025
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Purpose: To determine if melatonin-enriched culture media could offset loss of imprinting in mouse concepti.
Methods: Zygotes were cultured to blastocyst stage under optimized conditions in melatonin-supplemented media at either 10 M (MT 10) or 10 M (MT 10), or without supplementation (Culture + embryo transfer, or ET, positive control). Blastocysts were also developed in vivo (ET negative control).
Biol Psychiatry
September 2025
Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA; Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Canada; Division of Endocrinology, Children's Hospital LA, Los Angeles, CA; Department of Pediatrics, Keck Scho
Background: Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of psychosomatic disorders in adolescence and adulthood. Most investigations into biological processes that have been perturbed by ELA have profiled DNA methylation in whole blood and coalesced around perturbations of immunobiology being centrally insulted by ELA.
Methods: To identify novel molecular signatures that are enduringly perturbed by childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT, n = 7, 4M 3F) or maltreatment in infancy (MALT, n = 6, 3M 3F).
Nucleic Acids Res
September 2025
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.
The mammary gland, which primarily develops postnatally, undergoes significant changes during pregnancy and lactation to facilitate milk production. Through the generation and analysis of 480 transcriptomes, we provide the most detailed allelic expression map of the mammary gland, cataloguing cell-type-specific expression from ex-vivo purified cell populations over 10 developmental stages, enabling comparative analysis. The work identifies genes involved in the mammary gland cycle, parental-origin-specific and genetic background-specific expression at cellular and temporal resolution, genes associated with human lactation disorders and breast cancer.
View Article and Find Full Text PDFStem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFCommun Biol
September 2025
UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of maternally-inherited UBE3A. In neurons, paternally-inherited UBE3A is silenced in cis by a long non-coding RNA called Ube3a-ATS. Here, we found that Neisseria meningitidis Cas9 with two mutations (D15A and H587A) in the nuclease domains (dNmCas9) can unsilence the dormant paternal Ube3a allele in mouse and human neurons when targeted to Snord115 snoRNA genes located in introns of Ube3a-ATS.
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