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How do genes that escape from X‐chromosome inactivation contribute to Turner syndrome?
Author(s) -
Peeters Samantha B.,
Korecki Andrea J.,
Baldry Sarah E.L.,
Yang Christine,
Tosefsky Kira,
Balaton Bradley P.,
Simpson Elizabeth M.,
Brown Carolyn J.
Publication year - 2019
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31672
Subject(s) - gene silencing , gene , biology , x inactivation , dosage compensation , genetics , x chromosome , xist , skewed x inactivation , microrna , phenotype
X‐chromosome inactivation generally results in dosage equivalence for expression of X‐linked genes between 46,XY males and 46,XX females. The 20–30% of genes that escape silencing are thus candidates for having a role in the phenotype of Turner syndrome. Understanding which genes escape from silencing, and how they avoid this chromosome‐wide inactivation is therefore an important step toward understanding Turner Syndrome. We have examined the mechanism of escape using a previously reported knock‐in of a BAC containing the human escape gene RPS4X in mouse. We now demonstrate that escape from inactivation for RPS4X is already established by embryonic Day 9.5, and that both silencing and escape are faithfully maintained across the lifespan. No overt abnormalities were observed for transgenic mice up to 1 year of age despite robust transcription of the human RPS4X gene with no detectable downregulation of the mouse homolog. However, there was no significant increase in protein levels, suggesting translational compensation in the mouse. Finally, while many of the protein‐coding genes have been assessed for their inactivation status, less is known about the X‐linked RNA genes, and we propose that for many microRNA genes their inactivation status can be predicted as they are intronic to genes for which the inactivation status is known.