title: X-inactivation profile reveals extensive variability in X-linked gene expression in females.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. lcarrel@psu.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Carrel
authors.forename: Huntington F
authors.initials: HF
authors.lastname: Willard
mesh_terms: D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D010641:Phenotype; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D012727:Sex Characteristics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; C077885:XIST non-coding RNA