Man to Mouse—Lessons Learned from the Distal End of the Human X Chromosome
- Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg, Germany
This extract was created in the absence of an abstract.
Conservation between human and murine X chromosomes has been accepted as an incontrovertible principle for a long time and was generally envisaged as a powerful model system for the evolution of vertebrate sex chromosomes. In fact, the original postulate of Ohno (1973) that the constraints imposed by X-inactivation would conserve genes on the mammalian X chromosomes was reevaluated to become a fundamental law underlying sex chromosome evolution.
Contrasting this overall picture of harmony, the most distal band of the human X chromosome (Xp22.3) reveals a unique and so far unprecedented picture of chromosomal rearrangements during the evolution in eutherian mammals. The result of efforts toward the mapping of murine homologs of human X chromosomal genes have not only illustrated the massive reshuffling of X chromosomes during their evolution but also refined our understanding of mouse models for certain X chromosomal human genetic disorders.
Human X Chromosome Genes with Murine Homologs Autosomal or Absent
Clearly the genes residing in the pseudoautosomal region (PAR1) of the human sex chromosomes are exceptional in their relative chromosomal localization in man and mouse. In 1992, Disteche et al. reported the first instance of a human pseudoautosomal gene with an autosomal localization in mouse. The gene for the α subunit of the granulocyte macrophage colony stimulating factor receptor (CSF2RA) resides on chromosome 19 in mouse (Disteche et al. 1992). This case indicated for the first time an incomplete conservation between the mouse and human X chromosomes and suggested that the genetic composition of the pseudoautosomal region may vary among eutherian mammals, probably because of chromosomal rearrangements. Disteche’s initial assumption was later confirmed by mapping additional murine homologs of human pseudoautosomal genes to mouse autosomes. The α chain of the heterodimeric interleukin-3 receptor (IL3RA) is encoded by a gene closely linked to the CSF2A receptor locus inPAR1 in humans (Kremer et al. 1993), yet its …
