title: Skewing of X-inactivation ratios in blood cells of aging women is confirmed by independent methodologies.
abstract: 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.
authors.affiliation: Research Centre, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. lbusque.hmr@ssss.gouv.qc.ca
authors.forename: Lambert
authors.initials: L
authors.lastname: Busque
authors.forename: Yves
authors.initials: Y
authors.lastname: Paquette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Provost
authors.forename: Denis-Claude
authors.initials: DC
authors.lastname: Roy
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Luigina
authors.initials: L
authors.lastname: Mollica
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009504:Neutrophils / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D049951:X Chromosome Inactivation / Q000235:genetics*