Non-Additive Interactions between Monomorphic and Polymorphic Loci: A Theoretical Explanation of the Genetic Underpinning for Complex Traits pp. 133-148
Authors: (Shinji Ijichi, Naomi Ijichi, Yukina Ijichi, Hisami Sameshima, Yoshinori Saeki, William W. Hall, Hirofumi Morioka, Health Service Center, Kagoshima University, Korimoto, Kagoshima, Japan, and others)
Abstract: Molecular insight of non-additive interactions between genes (epistasis in the broad sense) suggests that the inter-gene interactions may involve not only alleles at polymorphic loci but also monomorphic gene regions. Here, a theoretical contribution of monomorphic loci to the inter-gene network is proposed as the universal underpinning for the phenotypic variation in continuous (quantitative) traits. In this framework, the difficulty in detecting the causal variant alleles at the involved polymorphic loci in some human conditions can be plausibly explained by the involvement of monomorphic loci and the participation of functionally random genetic backgrounds. To show conceptually the epistatic functions of the monomorphic loci involvement, artificially simplified models with pauci- or mono-morphic loci which have the functional roles for the phenotype were exemplified. In order to simulate the maintenance of variation in some quantitative traits from generation to generation, a fully random contribution determined by the random genetic backgrounds was substituted for the supposed non-additive and reversible manner of the epistasis or for a possible balanced mixture of positive and negative epistatic effects without the reversibility of gene effects. This novel monolithic interpretation of the missing heritability problem in quantitative geneticssuggests the possible presence of human extreme conditions (or diseases) without any links to specific alleles (causal variants) at polymorphic loci.
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