title: Global gene profiling and comprehensive bioinformatics analysis of a 46,XY female with pericentric inversion of the Y chromosome.
abstract: XY females are rare individuals who carry a Y chromosome but are phenotypically female. In approximately 80-90% of these cases, there are no mutations in the SRY gene, a testis-determining gene on the short arm of the Y chromosome, and the pathophysiology of XY females without SRY mutation remains unclear. In the present study, we used a molecular data mining technique to analyze the pathophysiology of an XY female with functional SRY and pericentric inversion of the Y chromosome, and compared the results with those of a normal male. Interestingly, upregulations of numerous genes included in the development category of the Biological Process ontology, including genes associated with sex determination and organ morphogenesis, were seen in the patient. Additionally, the transforming growth factor-beta (TGF-beta) signaling pathway and Wnt signaling pathway, in which most cell-cell interactions during embryonic development are involved, were altered. Alterations in the expression of numerous genes at the developmental stage, including alterations at both the gene and pathway levels, may persist as a vestige of anomalies of sex differentiation that presumably began in the fetal period. The present study indicates that a data mining technique using bioinformatics contributes to identification of not only genes responsible for birth defects, but also disorders of sex development (DSD)-specific pathways, and that this kind of analysis is an important tool for clarifying the pathophysiology of human idiopathic XY gonadal dysgenesis. Our findings could serve as one of the basic datasets which will be used for future follow-up investigations.
authors.affiliation: Department of Animal Science, Kobe University, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mitsuhashi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Warita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Teruo
authors.initials: T
authors.lastname: Sugawara
authors.forename: Fumio
authors.initials: F
authors.lastname: Hayashi
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ebina
authors.forename: Hideto
authors.initials: H
authors.lastname: Yamada
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nanmori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kant
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
mesh_terms: D000293:Adolescent; D041322:Chromosomes, Human, Y; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012729:Sex Chromosome Aberrations; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors