Abstract
We investigated the effect of aging on X chromosome inactivation by performing a longitudinal study in a population of 178 normal females. We examined X-inactivation ratios (fraction of cells with the same X chromosome active) in two sets of peripheral blood DNA samples collected about two decades apart. We observed a strong correlation between the ratios of individual females at the two time points and found no significant difference between the two sets of measurements. These observations indicate that aging, per se (as opposed to being “aged”), has little effect on X-inactivation. However, we also found that several females who were older than 60 years of age at the time of the first measurement acquired significant changes in the X-inactivation ratio. We speculate that, if X-inactivation skewing is a frequently acquired trait in older females, it is acquired as the result of a discontinuous or catastrophic process and is not the result of constant selection for or against hematopoietic stem cells with a particular X chromosome active.
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Acknowledgements
We are grateful to Kenneth Morgan for helpful suggestions and to Laurie Mecham, Tena Varvil, and Sylvie Croteau for administrative and technical assistance. This work was supported by grants from the Canadian Institutes of Health Research (to A.K.N.) and the National Institutes of Health (NIH R21ES/CA11607 to C.S.). It was also supported by a Public Health Services research grant to the Huntsman General Clinical Research Center at the University of Utah and grant no. M01-RR00064 from the National Center for Research Resources and by generous gifts from the W.M. Keck Foundation and from the George S. and Delores Doré Eccles Foundation. A.K.N. is a CIHR New Investigator.
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Sandovici, I., Naumova, A.K., Leppert, M. et al. A longitudinal study of X-inactivation ratio in human females. Hum Genet 115, 387–392 (2004). https://doi.org/10.1007/s00439-004-1177-8
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DOI: https://doi.org/10.1007/s00439-004-1177-8