Address of Corresponding Author

Cytogenet Genome Res 2005;111:260-265 (DOI: 10.1159/000086898)

  Abstract.

Recently, we reported that skewed X chromosome inactivation (XCI) was more common in women who had experienced a trisomic pregnancy as compared to control women. Rather than an overall shift in the distribution of skewing there appears to only be an excess of extreme (= 95%) skewing. Further analysis of our data reveals that the increase in skewed XCI is dependent on which chromosome is involved in the trisomy and how many trisomies the woman has experienced, although sample sizes in each group are small. In this review we discuss limitations of the commonly used assays of XCI, which use measurements of DNA methylation to infer skewing patterns, and review the data based on current knowledge of the causes of XCI skewing. Gonadal mosaicism, premature aging, loss of methylation at some CpGs, and X-linked mutations can all be considered as potential mechanisms explaining both increased risk of trisomy and skewed XCI. While further research is needed to evaluate the role of each of these, the association of trisomy with apparent skewed XCI in the mother offers new opportunities to clarify the risk factors for and causes of the high incidence of aneuploidy in human females.   

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Request reprints from Dr. Wendy Robinson
University of British Columbia Department of Medical Genetics
BC Research Institute for Children's and Women's Health
950 W 28^th Ave. (Room 3086), Vancouver, BC, V5Z 4H4 (Canada)
telephone: +1 (604) 875-3229; fax: +1 (604) 875-3120
e-mail: wprobins@interchange.ubc.ca

  Article Information

Supported by Canadian Institutes of Health Research grant MOP-38051 to W.P.R. K.B. is funded by the Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research, and the Interdisciplinary Women's Reproductive Health Training Program at the BC Research Institute for Children's and Women's Health.

Manuscript received 22 October 2004;
accepted in revised form for publication by R. Martin, 22 February 2005.
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 45