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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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HEMATOPOIESIS AND STEM CELLS

Brief Report

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

Lambert Busque13, Yves Paquette1, Sylvie Provost4, Denis-Claude Roy13, Ross L. Levine5, Luigina Mollica13, and D. Gary Gilliland6

1 Research Centre and 2 Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC; 3 University of Montreal, Montreal, QC; 4 Montreal Heart Institute, Montreal, QC; 5 Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY; and 6 Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Nonrandom X-chromosome inactivation (XCI), also known as skewing, has been documented in the blood cells of a significant proportion of normal aging women by the use of methylation-based assays at the polymorphic human androgen receptor locus (HUMARA). Recent data obtained with a new transcription-based XCI determination method, termed suppressive polymerase chain reaction (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 years with the use of HUMARA (n = 100), a TaqMan single nucleotide polymorphism (SNP) assay (n = 90), and the suppressive polymerase chain reaction (PCR) assay (n = 67). The 3 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 biologic phenomenon.


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