Genomic Sequencing to Detect Cross-Breeding Quality in Dogs: An Example Studying Disorders in Sexual Development

Area of Science:

• Veterinary Genetics
• Canine Reproduction
• Developmental Biology

Background:

• Disorders of Sexual Development (DSDs) in dogs share similarities with human conditions, arising from genetic or developmental anomalies.
• The French Bulldog breed exhibits a rising incidence of DSDs, coinciding with its increasing popularity.
• Understanding the genetic basis of DSDs is crucial for breed health management.

Purpose of the Study:

• To genetically characterize DSDs in a French Bulldog with ambiguous genitalia.
• To investigate the influence of breeding practices on genetic diversity within the French Bulldog breed.
• To identify potential genetic factors contributing to DSDs in this breed.

Main Methods:

• Comprehensive genetic analysis including conventional cytogenetics and deep sequencing.
• Comparative genomics: Brutus's genome compared to three other male French Bulldogs and the canine reference genome (CanFam6).
• Analysis of Robertsonian fusion, sex-determining region (SRY) gene, Single Nucleotide Variants (SNVs), and runs of homozygosity (ROH).

Main Results:

• A Robertsonian fusion on chromosome 23, a known cause of sex reversal syndrome, was identified.
• Mosaicism (78,XX/77,XX) and absence of the SRY gene were detected.
• Elevated homozygosity (50% greater ROH length) indicated potential sibling mating, suggesting inbreeding impacts DSD incidence.

Conclusions:

• While direct causative genes for Brutus's DSD phenotype were not identified, four candidate loci require further study.
• A more robust canine reference genome is needed for accurate phenotype-gene association.
• Uncontrolled breeding practices in French Bulldogs contribute to DSDs and reduced genetic diversity, necessitating strategic genetic management.