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Molecular mechanisms of X-inactivation in voles of genus Microtus

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The XIST gene from all four vole species has been cloned and characterised in some detail. Genetic mapping experiments have been carried out to localise XIST and a number of other X-linked genes on the vole X chromosomes. These studies have provided important insights into the relationship of the Xic and constitutive heterochromatin blocks in vole species. Information concerning the evolution of the mammalian X chromosome and the interrelationship of individual vole species has also been obtained. The M. transcaspicus XISTgene has been sequenced to completion. Approximately 70% of the gene has been sequenced in the other species under study. All species except M. arvalis exhibit a remarkably high degree of primary sequence conservation. The divergence of M. arvalis sequence is consistent with the hypothesis that non random X inactivation in F1 hybrids is attributable to variant Xicsequences. Future studies will attempt to identify which divergent sequences play a causative role in non random X inactivation. Data obtained will also beused to study evolution of the XIST gene and to determine aspects ofXIST RNA secondary structure by phylogenetic methods.

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