Exploring skeletal disorders in cattle and sheep: a WGS-based framework for diagnosis and classification

Area of Science:

• Veterinary Genetics
• Comparative Genomics
• Animal Science

Background:

• Genetic skeletal disorders in ruminants are diverse and often sporadic, with limited identified causal variants.
• Comprehensive genetic analyses of bovine and ovine skeletal defects are lacking.
• Understanding these genetic conditions is crucial for animal health and breeding.

Purpose of the Study:

• To establish a nosology for genetic skeletal disorders in cattle and sheep.
• To identify novel causative genetic variants in affected ruminants.
• To contribute genomic data to the classification of these developmental defects.

Main Methods:

• Literature review to compile existing knowledge and propose a nosology.
• Whole-genome sequencing (WGS) of affected bovine and ovine cases.
• Bioinformatic analysis to identify single nucleotide variants (SNVs), small insertions/deletions (indels), and aneuploidies.

Main Results:

• A nosology encompassing 43 disorders and 45 genes was proposed, including horn traits.
• Genomic analysis identified 17 candidate variants (11 pathogenic, 6 likely pathogenic) for 12 disorders, and two aneuploidies.
• The molecular genetic diagnostic rate was 64%, with various inheritance patterns detected.

Conclusions:

• Genomic analysis highlights significant heterogeneity in genetic skeletal disorders.
• A proposed nosology offers a framework for precise differential diagnosis in veterinary medicine.
• WGS is a powerful tool for enhancing genetic disease diagnosis in ruminants.