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Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms

AutorMitchell, Emma; Klein, Shifra L.; Argyropoulos, Kimon V.; Sharma, Ali; Chan, Robin B.; Gal Toth, Judit; Barboza, Luendreo; Bavley, Charlotte; Bortolozzi, Analía ; Chen, Qiuying; Liu, Bingfang; Ingenito, Joanne; Mark, Willie; Dudakov, Jarrod; Gross, Steven; Di Paolo, Gilberto; Artigas, Francesc ; van den Brink, Marcel; Toth, Miklos
Palabras claveBiological sciences
Genetics
Neurosciences
Fecha de publicación13-may-2016
EditorNature Publishing Group
CitaciónNature Communications 7 (11492): 2016
ResumenParental 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.
Versión del editorhttp://dx.doi.org/10.1038/ncomms11492
URIhttp://hdl.handle.net/10261/132753
DOI10.1038/ncomms11492
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