全基因组测序鉴定出犬类睾丸/卵睾型XX性发育障碍相关的PADI6错义多态性。

Whole genome sequencing identifies a missense polymorphism in PADI6 associated with testicular/ovotesticular XX disorder of sex development in dogs.

作者信息

Nowacka-Woszuk Joanna, Stachowiak Monika, Szczerbal Izabela, Szydlowski Maciej, Szabelska-Beresewicz Alicja, Zyprych-Walczak Joanna, Krzeminska Paulina, Nowak Tomasz, Lukomska Anna, Ligocka Zuzanna, Biezynski Janusz, Dzimira Stanislaw, Nizanski Wojciech, Switonski Marek

机构信息

Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637 Poznan, Poland.

Department of Mathematical and Statistical Methods, Poznan University of Life Sciences, Wojska Polskiego 28, 60-637 Poznan, Poland.

出版信息

Genomics. 2022 Jul;114(4):110389. doi: 10.1016/j.ygeno.2022.110389. Epub 2022 May 18.

DOI:10.1016/j.ygeno.2022.110389

PMID:35597501

Abstract

Disorders of sex development (DSDs) are congenital malformations defined as discrepancies between sex chromosomes and phenotypical sex. Testicular or ovotesticular XX DSDs are frequently observed in female dogs, while monogenic XY DSDs are less frequent. Here, we applied whole genome sequencing (WGS) to search for causative mutations in XX DSD females in French Bulldogs (FB) and American Staffordshire Terries (AST) and in XY DSD Yorkshire Terries (YT). The WGS results were validated by Sanger sequencing and ddPCR. It was shown that a missense SNP of the PADI6 gene, is significantly associated with the XX DSD (SRY-negative) phenotype in AST (P = 0.0051) and FB (P = 0.0306). On the contrary, we did not find any associated variant with XY DSD in YTs. Our study suggests that the genetic background of the XX DSD may be more complex and breed-specific.

摘要

性发育障碍（DSDs）是先天性畸形，定义为性染色体与表型性别之间的差异。睾丸或卵睾型XX DSD在雌性犬中经常出现，而单基因XY DSD则较少见。在此，我们应用全基因组测序（WGS）来寻找法国斗牛犬（FB）和美国斯塔福郡梗犬（AST）中XX DSD雌性以及XY DSD约克夏梗犬（YT）中的致病突变。WGS结果通过桑格测序和数字液滴PCR进行了验证。结果表明，PADI6基因的一个错义单核苷酸多态性与AST（P = 0.0051）和FB（P = 0.0306）中的XX DSD（SRY阴性）表型显著相关。相反，我们在YT中未发现与XY DSD相关的任何变异。我们的研究表明，XX DSD的遗传背景可能更复杂且具有品种特异性。