title: Epigenetic control of the critical region for premature ovarian failure on autosomal genes translocated to the X chromosome: a hypothesis.
abstract: Chromosomal rearrangements in Xq are frequently associated to premature ovarian failure (POF) and have contributed to define a POF "critical region" from Xq13.3 to Xq26. Search for X-linked genes responsible for the phenotype has been elusive as most rearrangements did not interrupt genes and many were mapped to gene deserts. We now report that ovary-expressed genes flanked autosomal breakpoints in four POF cases analyzed whose X chromosome breakpoints interrupted a gene poor region in Xq21, where no ovary-expressed candidate genes could be found. We also show that the global down regulation in the oocyte and up regulation in the ovary of X-linked genes compared to the autosomes is mainly due to genes in the POF "critical region". We thus propose that POF, in X;autosome balanced translocations, may not only be caused by haploinsufficiency, but also by a oocyte-specific position effect on autosomal genes, dependent on dosage compensation mechanisms operating on the active X chromosome in mammals.
authors.affiliation: Department of Molecular Biology and Functional Genomics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sala
authors.forename: Simone
authors.initials: S
authors.lastname: Alboresi
authors.forename: Silvia
authors.initials: S
authors.lastname: Bione
authors.forename: Serena
authors.initials: S
authors.lastname: Gilli
authors.forename: Mara
authors.initials: M
authors.lastname: Goegan
authors.forename: Tiziano
authors.initials: T
authors.lastname: Pramparo
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
mesh_terms: D001483:Base Sequence; D019457:Chromosome Breakage; D041321:Chromosomes, Human, X; D004303:Dosage Compensation, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic