title: Genetic and parent-of-origin influences on X chromosome choice in Xce heterozygous mice.
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.
authors.affiliation: Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Lisa Helbling
authors.initials: LH
authors.lastname: Chadwick
authors.forename: Huntington F
authors.initials: HF
authors.lastname: Willard
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D017931:DNA Primers; D050172:Genes, X-Linked / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D040582:Inheritance Patterns / Q000235:genetics*; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase