The essence of being human is the ability to communicate with language. This project addresses the questions what is the neural correlate of the capacity for language and what was the genetic nature of the transitions from a great ape-hominid precursor to modern H sapiens? Paul Broca's hypothesis that asymmetry is the feature that defines the human brain will be investigated in skull and brain structure and followed through the lead that a genetic determinant is located in a region of X-Y homology subject to change in the hominid lineage. It is argued that a series of changes influenced the timing of brain development. The Xq21.3/Yp sapiens-specific region of homology that includes the ProtocadherinX and ProtocadherinY gene pair is the salient candidate genomic region. The project investigates these hypotheses through i) great ape-human comparisons of skull structure including asymmetries, ii) great ape-human comparisons of asymmetries of the cellular structure of association cortex, iii) great ape-human comparisons of the structure and organization of inter-hemispheric connexions, iv) studies of the splice structure and expression of ProtocadherinX and Y, and investigations of the epigenetic control of sapiens-specific regions of homology, and v) studies of brain structure and the lateralisation of language in individuals with sex chromosome aneuploidies as exemplar anomalies of expression of the asymmetry determinant.