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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3472-3474.
Prepublished online as a Blood First Edition Paper on February 6, 2009; DOI 10.1182/blood-2008-12-195677.


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Submitted December 19, 2008
Accepted February 2, 2009

Skewing of X-inactivation ratios in blood cells of aging women is confirmed by independent methodologies

Lambert Busque*, Yves Paquette, Sylvie Provost, Denis-Claude Roy, Ross L. Levine, Luigina Mollica, and D. Gary Gilliland

Research Centre, Maisonneuve-Rosemont Hospital, Montreal, Canada
Montreal Heart Institute, Montreal, Canada
Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Canada
Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States
University of Montreal, Montreal, Canada
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

* Corresponding author; email: lbusque.hmr{at}ssss.gouv.qc.ca.

Non-random X chromosome inactivation (XCI), also known as skewing, has been documented in the blood cells of a significant proportion of normal aging women using methylation-based assays at the polymorphic human androgen receptor locus (HUMARA). Recent data obtained with a new transcription-based XCI determination method, termed "suppressive PCR", has shed controversy over the validity of XCI ratio results obtained with HUMARA. To resolve this disparity, we analyzed XCI in polymorphonuclear leukocytes of a large cohort of women aged 43 to 100 using HUMARA (n=100), a Taqman SNP assay (n=90), and the suppressive PCR assay (n=67). The three methods yielded similar skewing incidences (42%, 38%, and 40%, respectively), and highly concordant XCI ratios. This confirms that the skewing of XCI ratio seen in blood cells of aging women is a bona fide and robust biological phenomenon.


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