The effect of human-specific genetic variants on neuronal spinogenesis

Fundamental morphological and functional differences between the brains of animal models and humans are at least partially related to human-specific genes and genetic variants. As one of the structural underpinnings of brain function is the dendritic spine, we systematically queried a curated list of human-specific genes and genetic variants. We found that with the current knowledge base, 4.3% are linked to the dendritic spine. Functionally these genes converge on the cytoskeleton, Ca²⁺ signaling, small GTPases, NMDAR, and WNT signaling and trafficking suggesting human specific modification of canonical pathways. Significant gaps in knowledge are identified and concerted efforts are needed. Understanding human-specific genetic contributions to the unique features of the human brain will address existing translational gaps and facilitate the development of successful treatments for neuropsychiatric disorders, advance environmental neuroscience for early childhood intervention and environmental risk reduction in aging and dementia.