X-linked genes and mental functioning

• Published in: Human molecular genetics Vol. 14; no. suppl-1; pp. R27 - R32
• Main Author: Skuse, David H
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.04.2005; Oxford Publishing Limited (England)
• Subjects: Animals; Brain - metabolism; Cell Differentiation; Chromosomes, Human, X; Cognition; Dosage Compensation, Genetic; Female; Gene Dosage; Genetic Linkage; Genomic Imprinting; Humans; Male; Mice; Models, Biological; Models, Genetic; Neurons - metabolism; Sex Characteristics; Sex Factors; Turner Syndrome - genetics; X Chromosome
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddi112

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.