9 research outputs found
Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms
Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring.
Although trait transmission via sperm has been extensively researched, epidemiological
studies indicate the exclusive/prominent maternal transmission of many non-genetic traits.
Since maternal conditions impact the offspring during gametogenesis and through
fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive
germline and somatic effects; a concept that has not been previously studied. Here, we
dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized
anxiety/depression, to elementary behaviours/domains and their transmission mechanisms
in mice. We show that four anxiety/stress-reactive traits are transmitted via independent
iterative-somatic and gametic epigenetic mechanisms across multiple generations.
Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes
whose functions can be linked to the behavioural traits. Traits have generation-dependent
penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept
can refine current inheritance models of psychiatric diseases and facilitate the development
of better animal models and new therapeutic approaches.We are grateful for grant support R01-MH103102 and R21-MH103715 from the NIH to M.T., PO1-HD067244 and R37-HL87062 to S.S.G., 2R01-NS056049 to G.D.P., R01-HL069929, R01-AI080455 and R01-AI101406 to M.R.M. Also supported by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and grants SAF2015-68346-P to F.A. and PI13/01390 to A.B., co-financed by the European Regional Development Fund. E.M. was supported in part by NIH T32-GM073546.Peer reviewe
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