Department of Biosciences, Biotechnology and Environment, University of Bari, Via Orabona 4, 70124 Bari, Italy.
Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy.
Int J Mol Sci. 2024 Oct 6;25(19):10763. doi: 10.3390/ijms251910763.
Disorders of sexual development (DSDs) in dogs, similar to humans, arise from genetic mutations, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSDs in a French Bulldog named , exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. We utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of . The sequence data were compared to three other male French Bulldogs' genome sequences with typical reproductive anatomy, including 's father and the canine reference genome (CanFam6). We found a Robertsonian fusion involving chromosome 23 previously reported in dogs as a causative mutation responsible for sex reversal syndrome. Our findings revealed a 22% mosaicism (78,XX/77,XX), the absence of the sex-determining region () gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the run of homozygosity (ROH) analysis showed has a higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. Although no direct causative genes for the DSD phenotype were identified, four candidate loci warrant further investigation. Our study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations.
犬类的性发育障碍（DSD）与人类相似，源于基因突变、性腺分化或表型性发育。法国斗牛犬作为一种受欢迎程度和需求急剧上升的犬种，其 DSD 发病率也显著增加。本研究旨在描述一只名为 的法国斗牛犬的 DSD 遗传基础，该犬具有两性生殖器官和内部性器官，同时探讨繁殖实践对该品种遗传多样性的影响。我们采用综合方法，结合常规细胞遗传学、分子技术和深度测序，研究了 的遗传特征。将序列数据与其他三只具有典型生殖器官解剖结构的雄性法国斗牛犬的基因组序列进行比较，包括 的父亲和犬参考基因组（CanFam6）。我们发现了一种先前在犬中报道的罗伯逊易位融合，该融合涉及染色体 23，是导致性反转综合征的致病突变。我们的研究结果显示，存在 22%的嵌合体（78,XX/77,XX），缺失性别决定区（）基因，存在 43 个独特的单核苷酸变异（SNVs），这些变异并非来自父亲。值得注意的是，纯合子片段分析（ROH）显示，与其他法国斗牛犬相比， 具有更多的纯合子片段，这些片段的总长度比平均值长 50%，强烈表明这只狗是兄弟姐妹交配的产物。虽然没有发现直接导致 DSD 表型的基因，但有四个候选基因座值得进一步研究。我们的研究强调了需要更好地注释和管理参考犬基因组，以确定任何特定表型的致病基因，提示了犬类 DSD 表型的潜在遗传基础，并强调了法国斗牛犬不受控制的繁殖实践的后果。这些发现突出了实施战略性遗传管理以保护犬类群体遗传健康和多样性的重要性。
