title: Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain.
abstract: Genes escaping X-inactivation are predicted to contribute to differences in gene dosage between the sexes and are the prime candidates for being involved in the phenotype observed in individuals with X chromosome aneuploidies. Of particular interest is ProtocadherinX (PCDH11X or PCDHX), a recently described gene expressed in brain. In humans, PCDH11X has a homologue on the Y chromosome and is predicted to escape from X-inactivation. Employing bisulphite sequencing analysis we found absence of CpG island methylation on both the active and the inactive X chromosomes, providing a strong indication that PCDH11X escapes inactivation in humans. Furthermore, a sexual dimorphism in levels of expression in brain tissue was observed by quantitative real-time PCR, with females presenting an up to 2-fold excess in the abundance of PCDH11X transcripts. We relate these findings to sexually dimorphic traits in the human brain. Interestingly, PCDH11X/Y gene pair is unique to Homo sapiens, since the X-linked gene was transposed to the Y chromosome after the human-chimpanzee lineages split. Although no differences in promoter methylation were found between humans and chimpanzees, evidence of an upregulation of PCDH11X in humans deserves further investigation.
authors.affiliation: IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, R. Dr Roberto Frias, S/N, 4200-465, Porto, Portugal. alopes@ipatimup.pt
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Lopes
authors.forename: Norman
authors.initials: N
authors.lastname: Ross
authors.forename: James
authors.initials: J
authors.lastname: Close
authors.forename: Adam
authors.initials: A
authors.lastname: Dagnall
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Crow
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D002679:Pan troglodytes / Q000235:genetics; D000091363:Protocadherins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
chemical_list: D015820:Cadherins; C404498:PCDH11X protein, human; D000091363:Protocadherins