TY - JOUR
T1 - X-inactivation profile reveals extensive variability in X-linked gene expression in females
AU - Carrel, Laura
AU - Willard, Huntington F.
N1 - Funding Information:
Acknowledgements We thank M. Risio, E. David and their staffs for pathology, M. Cilli for mouse surgery, R. Albano, A. Ferraro and R. Lo Noce for technical assistance, and M. Belluardo for computational analysis. We thank A.Cignetto for secretarial assistance. G.S. is the recipient of an AIRC fellowship. This research was supported by AIRC, CNR-MIUR, FIRB-MIUR, MIUR-PRIN and the Foundations CRT and ‘Compagnia di San Paolo’.
Funding Information:
Acknowledgements We thank M. Ross for sharing information before publication and gratefully acknowledge technical assistance from G. Nickel, K. Trevarthen, J. Dunn, A. Cottle and M. Moon. This work was supported in part by a National Institutes of Health research grant to H.F.W. and L.C.
PY - 2005/3/17
Y1 - 2005/3/17
N2 - In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation. However, some genes escape X-inactivation and are expressed from both the active and inactive X chromosome. Such genes are potential contributors to sexually dimorphic traits, to phenotypic variability among females heterozygous for X-linked conditions, and to clinical abnormalities in patients with abnormal X chromosomes. Here, we present a comprehensive X-inactivation profile of the human X chromosome, representing an estimated 95% of assayable genes in fibroblast-based test systems. In total, about 15% of X-linked genes escape inactivation to some degree, and the proportion of genes escaping inactivation differs dramatically between different regions of the X chromosome, reflecting the evolutionary history of the sex chromosomes. An additional 10% of X-linked genes show variable patterns of inactivation and are expressed to different extents from some inactive X chromosomes. This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females.
AB - In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation. However, some genes escape X-inactivation and are expressed from both the active and inactive X chromosome. Such genes are potential contributors to sexually dimorphic traits, to phenotypic variability among females heterozygous for X-linked conditions, and to clinical abnormalities in patients with abnormal X chromosomes. Here, we present a comprehensive X-inactivation profile of the human X chromosome, representing an estimated 95% of assayable genes in fibroblast-based test systems. In total, about 15% of X-linked genes escape inactivation to some degree, and the proportion of genes escaping inactivation differs dramatically between different regions of the X chromosome, reflecting the evolutionary history of the sex chromosomes. An additional 10% of X-linked genes show variable patterns of inactivation and are expressed to different extents from some inactive X chromosomes. This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females.
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U2 - 10.1038/nature03479
DO - 10.1038/nature03479
M3 - Article
C2 - 15772666
AN - SCOPUS:15244353967
SN - 0028-0836
VL - 434
SP - 400
EP - 404
JO - Nature
JF - Nature
IS - 7031
ER -