Genetic and parent-of-origin influences on X chromosome choice in Xce heterozygous mice

Mamm Genome. 2005 Sep;16(9):691-9. doi: 10.1007/s00335-005-0059-2. Epub 2005 Oct 20.

Abstract

X chromosome inactivation is unique among dosage compensation mechanisms in that the two X chromosomes in females are treated differently within the same cell; one X chromosome is stably silenced while the other remains active. It is widely believed that, when X inactivation is initiated, each cell makes a random choice of which X chromosome will be silenced. In mice, only one genetic locus, the X-linked X controlling element (X ce), is known to influence this choice, because animals that are heterozygous at X ce have X-inactivation patterns that differ markedly from a mean of 0.50. To document other genetic and epigenetic influences on choice, we have performed a population-based study of the effect of X ce genotype on X-inactivation patterns. In B 6 CAST F(1) females (X ce(b)/X ce(c)), the X-inactivation pattern followed a symmetric distribution with a mean of 0.29 (SD=0.08). Surprisingly, however, in a population of X ce(b)/X ce(c) heterozygous B 6 CAST F(2) females, we observed significant differences in both the mean (p=0.004) and variance (p=0.004) of the X-inactivation patterns. This finding is incompatible with a single-locus model and suggests that additional genetic factors also influence X chromosome choice. We show that both parent-of-origin and naturally occurring genetic variation at autosomal loci contribute to these differences. Taken together, these data reveal further genetic complexity in this epigenetic control pathway.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Crosses, Genetic
  • Cyclin-Dependent Kinases / genetics
  • DNA Primers
  • Genes, X-Linked / genetics*
  • Genetic Variation*
  • Genotype
  • Inheritance Patterns / genetics*
  • Mice
  • Microsatellite Repeats / genetics
  • Models, Genetic*
  • Protein-Serine-Threonine Kinases / genetics
  • X Chromosome Inactivation / genetics*

Substances

  • DNA Primers
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • PCTAIRE-1 protein kinase