title: Elucidation of distinctive genomic DNA structures in patients with 46,XX testicular disorders of sex development using genome wide analyses.
abstract: OBJECTIVE
  Although several genes, including the SRY gene, are involved in testicular differentiation, the entire mechanism of this differentiation remains unclear. We performed genome wide analysis in patients with 46,XX testicular disorders of sex development to comprehensively elucidate the mechanisms of testicular differentiation.
  
  
  METHODS
  Whole genomic DNA was extracted from the peripheral blood of 4 patients with 46,XX testicular disorders of sex development who were SRY negative. Genomic DNA was hybridized to a GeneChip® human mapping 250K array set. Compared to normal female data, we detected common loss of heterozygosity and copy number variation regions in 4 patients using Genotyping Console™ software.
  
  
  RESULTS
  Loss of heterozygosity was detected in 19 regions of 11 chromosomes. A total of 27 genes or nearby genomic areas were included in the applicable regions. Copy number loss was recognized in 13 regions of 10 chromosomes, and these regions included 55 genes. Copy number gain was detected in 6 regions of 4 chromosomes, which included the upstream region of the SOX3 gene.
  
  
  CONCLUSIONS
  The regions with loss of heterozygosity did not contain genes associated with testicular differentiation. However, the upstream area of the SOX3 gene, which is located in Xq27.1, was included in the region of copy number gain. These results suggest that high expression of the SOX3 gene led to testicular differentiation despite SRY gene loss. As this applicable area is not within a coding region, genome wide analyses were valuable for detecting the novel regions associated with testicular differentiation.
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kamisawa
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Moritoki
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakane
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurokawa
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya and Department of Urology, Fukushima Medical University School of Medicine, Fukushima (YK), Japan. Electronic address: yutaro@med.nagoya-cu.ac.jp.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D004247:DNA / Q000032:analysis*; D012734:Disorders of Sex Development / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans
chemical_list: D004247:DNA
keywords: comparative genomic hybridization; disorders of sex development; sex differentiation; testis