Despite a strong genetic contribution to obesity and diabetes, genome wide association studies have identiﬁed variants that can only explain less than 10% of the observed heritability. This discrepancy, known as the missing heritability problem, has stimulated research aimed at understanding the bases and possible explanations for this observation. One prominent hypothesis, now supported by substantial amount of experimental evidence, points at epigenetic inheritance. Parental environmental experiences indeed cause phenotypic variation in unexposed offspring through geneticindependent epigenetic mechanisms. Beside environmentally acquired epigenetic inheritance, published ﬁndings and our own preliminary data suggest that parental genetics can also control phenotypic variation in the wild-type progeny through epigenetic mechanisms. A preliminary in silico screening in our lab identiﬁed several potential non-canonical epigenetic modiﬁers. Aim of this PhD project is to further characterise one of these candidates by coupling systemic phenotyping in the mouse with state-of-the art bulk and single cell molecular proﬁlings.
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Posavec Marjanović M1,2, Hurtado-Bagès S2,3, Lassi M4,5, Valero V3, Malinverni R3, Delage H6, Navarro M7,8, Corujo D3, Guberovic I3, Douet J3, Gama-Perez P9, Garcia-Roves PM9, Ahel I10, Ladurner AG11, Yanes O7,8, Bouvet P6,12, Suelves M1, Teperino R4,5,13, Pospisilik JA13, Buschbeck M1,3.