X-linked genes and mental functioning.
The X-chromosome has played a crucial role in the development of sexually selected characteristics for over 300 million years. During that time it has accumulated a disproportionate number of genes concerned with mental functions. Evidence is emerging, from studies of both humans and mice, for a general influence upon intelligence (as indicated by the large number of X-linked mental retardation syndromes). In addition, there is evidence for relatively specific effects of X-linked genes on social-cognition and emotional regulation. Sexually dimorphic processes could be influenced by several mechanisms. First, a small number of X-linked genes are apparently expressed differently in male and female brains in mouse models. Secondly, many human X-linked genes outside the X-Y pairing pseudoautosomal regions escape X-inactivation. Dosage differences in the expression of such genes (which might comprise at least 20% of the total) are likely to play an important role in male-female neural differentiation. To date, little is known about the process but clues can be gleaned from the study of X-monosomic females who are haploinsufficient for expression of all non-inactivated genes relative to 46,XX females. Finally, from studies of both X-monosomic humans (45,X) and mice (39,X), we are learning more about the influences of X-linked imprinted genes upon brain structure and function. Surprising specificity of effects has been described in both species, and identification of candidate genes cannot now be far off.
Skuse
David H
DH
Behavioural and Brain Sciences Unit, Institute of Child Health, London, UK. dskuse@ich.ucl.ac.uk
D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D041321:Chromosomes, Human, X; D003071:Cognition; D004303:Dosage Compensation, Genetic; D005260:Female; D018628:Gene Dosage; D008040:Genetic Linkage; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D012727:Sex Characteristics; D012737:Sex Factors; D014424:Turner Syndrome / Q000235:genetics; D014960:X Chromosome