Title

Bovine X chromosome inactivation and epimutation of X-linked genes in deceased bovine clones

Date of Completion

January 2004

Keywords

Biology, Molecular

Degree

Ph.D.

Abstract

This thesis investigated a unique biological and developmental phenomenon: X chromosome inactivation in bovine and bovine clones. It is speculated that low somatic cloning efficiency and abnormalities in cloned animals are due to inaccurate epigenetic reprogramming. This work studied the epigenetic reprogramming in cloned cattle, using X chromosome inactivation as model system. This study has shown that bovine X chromosome inactivation is random in somatic cells, like human and mice; is imprinted in placenta, same as mice but different from human. It has demonstrated that the structure and function of Tsix, a gene that is thought to regulate imprinted XCI in mice, are similar to mice but not to human. In this work, XCI has been shown normal in live clones, abnormal in deceased clones. Although aberrant expression patterns of X-linked genes vary from clone to clone, organ to organ, the following certain aberrant patterns were identified in every deceased clones analyzed: missing of 3 end of Xist transcript and hyper- or hypo-methylation of Xist; skewed XCI in lung. The inaccurate reprogramming of the two epigenetic marks, Xist transcript and methylation, are correlated with aberrant expression patterns of other X-linked genes, and may contribute to the death of clones. ^