Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Apr 9;113(15):3472-4.
doi: 10.1182/blood-2008-12-195677. Epub 2009 Feb 6.

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

Lambert Busque  1 , Yves Paquette, Sylvie Provost, Denis-Claude Roy, Ross L Levine, Luigina Mollica, D Gary Gilliland
Affiliations

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

Lambert Busque et al. Blood. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Correlation of XCI patterns obtained with the use of 3 different methods. (A) HUMARA assay versus TaqMan SNP assay at the IDS locus. For each individual, the %Sup measured by HUMARA was compared with the percentage of IDS allele obtained with the TaqMan SNP assay, which was quantitatively closer to the HUMARA value. Data from both assays were available for 90 women. (B) HUMARA assay versus suppressive PCR assay at the IDS locus. The %Sup obtained by HUMARA was compared with the percentage of IDS allele obtained with the suppressive PCR assay, which was quantitatively closer to the HUMARA value. Data from both assays were available for 67 women. (C) TaqMan SNP assay versus suppressive PCR assay. The percentage of IDS allele obtained with the TaqMan SNP assay was compared with that obtained with the suppressive PCR assay. Data from both assays were available for 60 women. Those aged 44 to 65 years are represented by ▵, whereas those older than 65 years are represented by ●.
See this image and copyright information in PMC

Comment in

References

    1. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961;190:372–373. - PubMed
    1. Busque L, Mio R, Mattioli J, et al. Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood. 1996;88:59–65. - PubMed
    1. Gale RE, Fielding AK, Harrison CN, Linch DC. Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age. Br J Haematol. 1997;98:512–519. - PubMed
    1. Tonon L, Bergamaschi G, Dellavecchia C, et al. Unbalanced X-chromosome inactivation in haemopoietic cells from normal women. Br J Haematol. 1998;102:996–1003. - PubMed
    1. Sharp A, Robinson D, Jacobs P. Age- and tissue-specific variation of X chromosome inactivation ratios in normal women. Hum Genet. 2000;107:343–349. - PubMed

Publication types