Comparison of X chromosome inactivation patterns in multiple tissues from human females

Douglas C Bittel ^1*, Mariana Theodoro ¹, Nataliya Kibiryeva ¹, William Fischer ¹, Zohreh Talebizadeh ¹ and Merlin G Butler ²

¹ Children's Mercy Hospital and Clinics, United States
² Children's Mercy Hospitals and Clinics, United States

^* To whom correspondence should be addressed. E-mail: dbittel{at}cmh.edu.

Accepted 27 November 2007

Abstract

Background: X-chromosome inactivation (XCI) is the mechanism by which gene dosage uniformity is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome and is thought to occur at random. For molecular genetic testing, tissues of convenience (e.g., blood) are commonly studied but the relationship with inaccessible tissues (e.g., brain) is poorly understood. For accessible tissues to be informative for genetic analysis, a high degree of concordance of genetic findings among tissue types would be required.

Objectives and Methods: To determine the relationship among multiple tissues within females at different ages (fetus to 82 years), we analyzed XCI patterns using the polymorphic androgen receptor (AR) gene assay using DNA isolated from 34 tissues representing the three embryonic germ layers in 26 different autopsies of human females without history of malignancy.

Results: Thirty three of the 280 tissue samples analyzed from 13 of the 26 females showed skewed XCI values (>80%:20%). However, the average XCI value was not significantly different among the tissues but a trend for increasing XCI variability was observed with age in blood and other tissues studied (e.g., the standard deviation for the 0-2 yr group was 9.9% compared to 14.8% in the >60 yr group). We found a significant correlation (rs = 0.51, p = 0.035) between XCI values for blood and/or spleen and brain tissue, as well as most other tissues representing the three embryonic germ layers.

Conclusions: In our study XCI data were comparable among accessible (e.g., blood) and inaccessible tissues (e.g., brain) in females at various ages and may be useful for genetic testing. A trend was seen for greater XCI variability with increasing age (particularly in older females, e.g., >60 years).

Keywords: Androgen receptor (AR) gene, Autopsy tissues, Germ layer, X-chromosome inactivation

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