title: Copy number variation in the region harboring SOX9 gene in dogs with testicular/ovotesticular disorder of sex development (78,XX; SRY-negative).
abstract: Although the disorder of sex development in dogs with female karyotype (XX DSD) is quite common, its molecular basis is still unclear. Among mutations underlying XX DSD in mammals are duplication of a long sequence upstream of the SOX9 gene (RevSex) and duplication of the SOX9 gene (also observed in dogs). We performed a comparative analysis of 16 XX DSD and 30 control female dogs, using FISH and MLPA approaches. Our study was focused on a region harboring SOX9 and a region orthologous to the human RevSex (CanRevSex), which was located by in silico analysis downstream of SOX9. Two highly polymorphic copy number variable regions (CNVRs): CNVR1 upstream of SOX9 and CNVR2 encompassing CanRevSex were identified. Although none of the detected copy number variants were specific to either affected or control animals, we observed that the average number of copies in CNVR1 was higher in XX DSD. No copy variation of SOX9 was observed. Our extensive studies have excluded duplication of SOX9 as the common cause of XX DSD in analyzed samples. However, it remains possible that the causative mutation is hidden in highly polymorphic CNVR1.
authors.affiliation: European Centre of Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Marcinkowska-Swojak
authors.affiliation: Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Szczerbal
authors.affiliation: Chair of Animal Breeding, Technische Universität München, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Pausch
authors.affiliation: Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Nowacka-Woszuk
authors.affiliation: Chair of Livestock Biotechnology, Technische Universität München, Germany.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Flisikowski
authors.affiliation: Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Dzimira
authors.affiliation: Department of Reproduction and Clinic of Farm Animals, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nizanski
authors.affiliation: CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, Vila Real, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Payan-Carreira
authors.affiliation: Chair of Animal Breeding, Technische Universität München, Germany.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Fries
authors.affiliation: European Centre of Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
authors.affiliation: Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Switonski
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056915:DNA Copy Number Variations; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D020440:Gene Duplication; D056726:Genetic Association Studies; D050090:Ovotesticular Disorders of Sex Development / Q000235:genetics / Q000662:veterinary*; D011110:Polymorphism, Genetic; D055758:SOX9 Transcription Factor / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D055758:SOX9 Transcription Factor