2009
DOI: 10.1182/blood-2008-12-195677
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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 poly… Show more

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Cited by 82 publications
(77 citation statements)
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“…Busque et al studied 100 women from elderly and young cohorts combined (mean age, 64 years) using HUMARA and 2 independent transcription clonality assays (one based on a quantitative allele-specific PCR and the other based on TaqMan-SNP) and found similar skewing incidences with the 3 different methods (40% ± 2%). The authors conclude that their results validate previous studies in which HUMARA assay document age-dependent skewing in females and that skewing of XCI ratio seen in blood cells of aging women is a genuine biologic phenomenon [6].…”
Section: Introductionsupporting
confidence: 85%
See 1 more Smart Citation
“…Busque et al studied 100 women from elderly and young cohorts combined (mean age, 64 years) using HUMARA and 2 independent transcription clonality assays (one based on a quantitative allele-specific PCR and the other based on TaqMan-SNP) and found similar skewing incidences with the 3 different methods (40% ± 2%). The authors conclude that their results validate previous studies in which HUMARA assay document age-dependent skewing in females and that skewing of XCI ratio seen in blood cells of aging women is a genuine biologic phenomenon [6].…”
Section: Introductionsupporting
confidence: 85%
“…Deviation from the theoretical 1:1 ratio between the 2 parental alleles is called skewing. Several reports using the HUMARA assay show that the incidence of skewing is relatively low at birth and in adult non-hematopoietic tissues, but higher and agedependent in hematopoietic cells, with 30-40% of healthy elderly women reported to have skewing (greater than 75% expression of one parental X chromosome) [5][6][7][8][9][10][11][12]. T lymphocytes show less evidence of skewing with age than neutrophils, presumably reflecting the neutrophils' short half-life, whereas T lymphocytes are long-living cells, and in consequence, some T cells are produced near the time of study but others are derived from earlier stem cells [11][12][13].…”
mentioning
confidence: 99%
“…Early indications of this phenomenon came from observations that the ratio of maternal to paternal X-chromosome inactivation is skewed in the blood of some otherwise healthy individuals, especially among the elderly. [1][2][3][4] Skewing can be seen in all hematopoietic lineages, consistent with an origin in HSCs, but is most easily seen in nucleated cells of the myeloid lineage because they are short lived and require continuous replenishment from HSCs. 5,6 Age-related CH does not arise from a simple depletion of HSCs, as the abundance of HSCs in human bone marrow actually increases in older people.…”
Section: Introductionmentioning
confidence: 99%
“…Recently, however, skewing of X inactivation in aging women was confirmed by two transcriptionalbased assays. 8 There are two main hypotheses as to why DS increases with age in cross-sectional studies. One is that DS increases with age within the same individual and the other is that DS is associated with life expectancy in women.…”
Section: Introductionmentioning
confidence: 99%