X-linked genes and mental functioning
Behavioural and Brain Sciences Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
* To whom correspondence should be addressed. Tel: +44 207 831 0975; Fax: +44 207 831 7050; Email: dskuse{at}ich.ucl.ac.uk
Received January 20, 2005; Revised February 3, 2005; Accepted February 17, 2005
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.
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