title: Methylation Patterns of SOX3, SOX9, and WNT4 Genes in Gonads of Dogs with XX (SRY-Negative) Disorder of Sexual Development.
abstract: Ovotesticular or testicular disorder of sexual development in dogs with female karyotype and lack of SRY (XX DSD) is a common sexual anomaly diagnosed in numerous breeds. The molecular background, however, remains unclear, and epigenetic mechanisms, including DNA methylation, have not been studied. The aim of our study was comparative methylation analysis of CpG islands in promoters of candidate genes for XX DSD: SOX9, SOX3, and WNT4. Methylation studies were performed on DNA extracted from formalin-fixed/paraffin-embedded or frozen gonads from 2 dogs with ovotesticular and 2 dogs with testicular XX DSD as well as control females (n = 4) and males (n = 2). Bisulfite-converted DNA was used for CpG methylation analysis using quantitative pyrosequencing. Promoter regions of SOX9 and WNT4 showed similar CpG methylation in each group, ranging from 0 to 5.5% and from 39 to 74%, respectively. The SOX3 promoter showed significantly higher methylation in the ovotesticular XX DSD cases and the testicular XX DSD and control males, suggesting that SOX3 methylation may play a role in canine XX DSD pathogenesis.
authors.affiliation: Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Salamon
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Flisikowski
authors.forename: Marek
authors.initials: M
authors.lastname: Switonski
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D012734:Disorders of Sex Development / Q000235:genetics*; D004285:Dogs; D005260:Female; D006066:Gonads / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D060528:Wnt4 Protein / Q000235:genetics*
chemical_list: D055758:SOX9 Transcription Factor; D055748:SOXB1 Transcription Factors; D060528:Wnt4 Protein
keywords: Disorder of sexual development; Dog; Intersexuality; Methylation; SOX3; SOX9; WNT4