Stochastic epistasis that is one of the characteristics of epistatic gene modules can have an important role in the maintenance of intraspecific population diversity. The effect of an epistatic modifier variant can vary in size and direction among the modifier careers on the basis of stochastic genetic individuality and the entire module effect can be also individually stochastic. This stochastic genetic contribution under a genetic background may be conditional upon the presence of a monomorphic switch locus in the gene module. The genetic background includes multiple modifier variants and the gene module is composed of the switch and the modifiers. The bell-shaped distribution of quantitative traits can be well simulated by the involvement of multiple stochastic epistatic modules. The phenotypic stochasticity makes the presence of switch and modifiers cryptic or missing in the research field and this cryptic gene networks can maintain and innovate in the phenotypic diversity under selection as a process of the evolution of complexity.
In the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), autistic characteristics in social interaction and communication are described as qualitative impairments. However, the difference between autistics and nonautistics in the draft of the 5th edition (DSM-5 draft) is quantitative rather than qualitative. The word “qualitative” is deleted in the draft text, and it is specified that the relation between social demands and individual limited capacities is critical for symptom manifestation (criterion C). Because the proposed levels of support requirement in the draft are mere observable outcomes of social vulnerability, the boundary between level 1 and nonautistic condition is determined by the relation between social demands and individual capacities. In addition to the introduction of the single category (autism spectrum disorder (ASD)) to cover the entire case spectrum, the DSM-5 draft is clearly based on a conviction that ASD is indistinguishable from the normal behavioral range. This concise review provides an explanation for this implicit paradigm shift from qualitative to quantitative. Importantly, the conditional role of social demands for symptom manifestation in the draft can be plausibly interpreted using a unique liability-probability model.
The ignorance of Helsinki declaration is continuing in Japan for approximately 20 years. More than 400 children including preschoolers with developmental conditions including temper tantrums, hyperactivity, and/or autistic characteristics have been already operated. The cranioplasty for isolated mild trigonocephaly had been empirically introduced by a physician to re-establish the brain spatial environment, and a government-granted and multi-centered clinical observation study is now in operation without scientific verification of the procedure's validity. The characteristic of the skull shape are too mild and sometimes too subtle to be recognized by the parents and health checkup doctors. A physician may tentatively and extraordinarily use an unproven procedure in exceptional circumstances where proven and effective interventions do not exist. However, the intervention must as soon as possible be subjected to scientific scrutiny according to ethical principles in order to stop the utilization in case of misprediction (no evidence of the efficacy).
The continuing prevalence of a highly heritable and hypo-reproductive extreme tail of a human neurobehavioral quantitative diversity suggests the reproductive majority retains the genetic mechanisms for extremes. From the perspective of stochastic epistasis, the effect of an epistatic modifier variant can randomly vary in both phenotypic value and effect direction among carriers depending on the genetic identity and the modifier carriers are ubiquitous in the population. The neutrality of the mean genetic effect in carriers ensures the survival of the variant under selection pressures. Functionally or metabolically related modifier variants make an epistatic network module and dozens of modules may be involved in the phenotype. To assess the significance of stochastic epistasis, a simplified module-based model was simulated. The individual repertoire of the modifier variants in a module also contributes in genetic identity, which determines the genetic contribution of each carrier modifier. Because the entire contribution of a module to phenotypic outcome is unpredictable in the model, the module effect represents the total contribution of related modifiers as a stochastic unit in simulations. As a result, the intrinsic compatibility between distributional robustness and quantitative changeability could mathematically be simulated using the model. The artificial normal distribution shape in large-sized simulations was preserved in each generation even if the lowest fitness tail was non-reproductive. The robustness of normality across generations is analogous to the real situation of complex human diversity, including neurodevelopmental conditions. The repeated regeneration of a non-reproductive extreme tail may be essential for survival and change of the reproductive majority, implying extremes for others. Further simulation to illustrate how the fitness of extreme individuals can be low across generations may be necessary to increase the plausibility of this stochastic epistasis model.
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