| Abstract: |
Nonrandom X-chromosome inactivation (XCI), also known as skewing, has been documented in the blood cells of a signifi-cant proportion of normal aging women by the use of methylation-based assays at the polymorphic human androgen re-ceptor locus (HUMARA). Recent data ob-tained with a new transcription-based XCI determination method, termed suppres-sive 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 reac-tion (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 © 2009 by The American Society of Hematology. |
| Keywords: |
adult; aged; aged, 80 and over; middle aged; human cell; single nucleotide polymorphism; polymorphism, single nucleotide; polymerase chain reaction; reproducibility of results; cohort analysis; gene locus; dna methylation; neutrophil; chromosomes, human, x; blood cell; x chromosome inactivation; androgen receptor; aging; dosage compensation, genetic; models, genetic; neutrophils
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