X-linked genes and mental functioning

Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R27-32. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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*