ABSTRACT
Accumulating evidence points out that sperm carry epigenetic instructions to embryo in the form of retained histones marks and RNA cargo that can transmit metabolic and behavioral traits to offspring. However, the mechanisms behind epigenetic inheritance of paternal environment are still poorly understood. Here, we curated male germ cells RNA-seq data and analyzed the expression profile of all known histone lysine writers and erasers enzymes across spermatogenesis, unraveling the developmental windows at which they are upregulated, and the specific activity related to canonical and non-canonical histone marks deposition and removal. We also characterized the epigenetic enzymes signature in the mature sperm RNA cargo, showing most of them positive translation at pre-cleavage zygote, suggesting that paternally-derived enzymes mRNA cooperate with maternal factors to embryo chromatin assembly. Our study shows several histone modifying enzymes not described yet in spermatogenesis and even more, important mechanistic aspects behind transgenerational epigenetics. Epigenetic enzymes not only can respond to environmental stressors, but could function as vectors of epigenetic information and participate in chromatin organization during maternal-to-zygote transition.
ABSTRACT
BACKGROUND: GenIO is a novel web-server, designed to assist clinical genomics researchers and medical doctors in the diagnostic process of rare genetic diseases. The tool identifies the most probable variants causing a rare disease, using the genomic and clinical information provided by a medical practitioner. Variants identified in a whole-genome, whole-exome or target sequencing studies are annotated, classified and filtered by clinical significance. Candidate genes associated with the patient's symptoms, suspected disease and complementary findings are identified to obtain a small manageable number of the most probable recessive and dominant candidate gene variants associated with the rare disease case. Additionally, following the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and recommendations, all potentially pathogenic variants that might be contributing to disease and secondary findings are identified. RESULTS: A retrospective study was performed on 40 patients with a diagnostic rate of 40%. All the known genes that were previously considered as disease causing were correctly identified in the final inherit model output lists. In previously undiagnosed cases, we had no additional yield. CONCLUSION: This unique, intuitive and user-friendly tool to assists medical doctors in the clinical genomics diagnostic process is openly available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .
Subject(s)
Rare Diseases/genetics , User-Computer Interface , Genetic Association Studies , Genotype , Humans , Internet , Phenotype , Rare Diseases/pathologyABSTRACT
We investigated an individual ability to identify whether choices were made freely or forced by external parameters. We capitalized on magical setups where the notion of psychological forcing constitutes a well trodden path. In live stage magic, a magician guessed cards from spectators while inquiring how freely they thought they had made the choice. Our data showed a marked blindness in the introspection of free choice. Spectators assigned comparable ratings when choosing the card that the magician deliberately forced them compared to any other card, even in classical forcing, where the magician literally handles a card to the participant This observation was paralleled by a laboratory experiment where we observed modest changes in subjective reports by factors with drastic effect in choice. Pupil dilatation, which is known to tag slow cognitive events related to memory and attention, constitutes an efficient fingerprint to index subjective and objective aspects of choice.
