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Mamm Genome. 2005 Sep;16(9):691-9. Epub 2005 Oct 20.

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

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  • 1Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.

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.

PMID:
16245026
[PubMed - indexed for MEDLINE]
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