Vorsanova Svetlana G, Zelenova Maria A, Yurov Yuri B, Iourov Ivan Y
Separated Structural Unit "Clinical Research Institute of Pediatrics at Pirogov Russian National Research Medical University named after Y.E Veltishev", Ministry of Health of Russian Federation, Moscow125412, Russian Federation.
Mental Health Research Center, Moscow117152, Russian Federation.
Curr Genomics. 2018 Apr;19(3):158-162. doi: 10.2174/1389202918666170719165339.
Behavioral sciences are inseparably related to genetics. A variety of neurobehavioral phenotypes are suggested to result from genomic variations. However, the contribution of genetic factors to common behavioral disorders (i.e. autism, schizophrenia, intellectual disability) remains to be understood when an attempt to link behavioral variability to a specific genomic change is made. Probably, the least appreciated genetic mechanism of debilitating neurobehavioral disorders is somatic mosaicism or the occurrence of genetically diverse (neuronal) cells in an individual's brain. Somatic mosaicism is assumed to affect directly the brain being associated with specific behavioral patterns. As shown in studies of chromosome abnormalities (syndromes), genetic mosaicism is able to change dynamically the phenotype due to inconsistency of abnormal cell proportions. Here, we hypothesize that brain-specific postzygotic changes of mosaicism levels are able to modulate variability of behavioral phenotypes. More precisely, behavioral phenotype variability in individuals exhibiting somatic mosaicism might correlate with changes in the amount of genetically abnormal cells throughout the lifespan. If proven, the hypothesis can be used as a basis for therapeutic interventions through regulating levels of somatic mosaicism to increase functioning and to improve overall condition of individuals with behavioral problems.
行为科学与遗传学有着千丝万缕的联系。多种神经行为表型被认为是由基因组变异导致的。然而，当试图将行为变异性与特定的基因组变化联系起来时，遗传因素对常见行为障碍（如自闭症、精神分裂症、智力障碍）的作用仍有待进一步了解。或许，导致神经行为障碍的最不为人所重视的遗传机制是体细胞镶嵌现象，即个体大脑中出现基因不同的（神经元）细胞。体细胞镶嵌现象被认为会直接影响与特定行为模式相关的大脑。正如染色体异常（综合征）研究所示，由于异常细胞比例不一致，遗传镶嵌现象能够动态改变表型。在此，我们假设大脑特异性的合子后镶嵌水平变化能够调节行为表型的变异性。更确切地说，表现出体细胞镶嵌现象的个体的行为表型变异性可能与一生中基因异常细胞数量的变化相关。如果这一假设得到证实，那么它可以作为通过调节体细胞镶嵌水平来增加功能并改善有行为问题个体的整体状况的治疗干预基础。
