TY - JOUR
T1 - Copy number variation in the region harboring SOX9 gene in dogs with testicular/ovotesticular disorder of sex development (78,XX; SRY-negative)
AU - Marcinkowska-Swojak, Malgorzata
AU - Szczerbal, Izabela
AU - Pausch, Hubert
AU - Nowacka-Woszuk, Joanna
AU - Flisikowski, Krzysztof
AU - Dzimira, Stanislaw
AU - Nizanski, Wojciech
AU - Payan-Carreira, Rita
AU - Fries, Ruedi
AU - Kozlowski, Piotr
AU - Switonski, Marek
N1 - Funding Information:
This study was financed by the National Science Center in Poland - grant 2012/05/B/NZ9/00907 and 2011/01/B/NZ5/02773. We wish to thank Dr. Alex Kind for his comments on the manuscript and Mrs Sylwia Salamon, M.Sc. for technical assistance.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84942884672&partnerID=8YFLogxK
U2 - 10.1038/srep14696
DO - 10.1038/srep14696
M3 - Article
C2 - 26423656
AN - SCOPUS:84942884672
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 14696
ER -