Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives
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Genetic control of non‑genetic inheritance in mammals: state‑of‑the‑art and perspectives A. Tomar1,2 · R. Teperino1,2 Received: 27 March 2020 / Accepted: 3 June 2020 © The Author(s) 2020
Abstract Thought to be directly and uniquely dependent from genotypes, the ontogeny of individual phenotypes is much more complicated. Individual genetics, environmental exposures, and their interaction are the three main determinants of individual’s phenotype. This picture has been further complicated a decade ago when the Lamarckian theory of acquired inheritance has been rekindled with the discovery of epigenetic inheritance, according to which acquired phenotypes can be transmitted through fertilization and affect phenotypes across generations. The results of Genome-Wide Association Studies have also highlighted a big degree of missing heritability in genetics and have provided hints that not only acquired phenotypes, but also individual’s genotypes affect phenotypes intergenerationally through indirect genetic effects. Here, we review available examples of indirect genetic effects in mammals, what is known of the underlying molecular mechanisms and their potential impact for our understanding of missing heritability, phenotypic variation. and individual disease risk.
Classical and extended heredity Years of genetics have attributed uniquely to genes (and genotypes) the ability to generate and transfer phenotypes across generations (Gayon 2016). In 1893, August Weismann in his thesis introduced the theory of heredity where he proposed that in multicellular organisms heritable information is transmitted from germ-plasm (germ cells) to the soma, and this movement is a one way road (Weismann 1893). This theoretical impenetrable barrier is referred to as the Weismann barrier and has blocked till a decade ago any possibility of acquired inheritance since no acquired information can be stored and transferred from the soma to the germline to be inherited (Sabour and Scholer 2012). Studies from the last decades have broken this dogma and shown that continuous phenotypic traits (such as body mass index—BMI, glucose tolerance, and blood pressure among others) are plastic, respond to environmental challenges during the lifetime and these responses can be inherited across * R. Teperino raffaele.teperino@helmholtz‑muenchen.de 1
Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany
2
two or more generations, through epigenetic mechanisms (Sabour and Scholer 2012; Skvortsova et al. 2018). This phenomenon, known as epigenetic inheritance, has constituted one of the biggest paradigm shifts in science of the recent years, and extends the classical concept of genetic inheritance to the non-genetic inheritance of acquired characteristics. Phenotypes are thus determined by both genetic and acquired (epigenetic) elements.
Genome‑Wide Association Studies and the Missing Heritability Genome-Wide Ass
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