Whole exome sequencing as a screening tool in dogs: A pilot study

Area of Science:

• Genomics
• Veterinary Genetics
• Molecular Diagnostics

Background:

• Whole-exome sequencing (WES) is a cost-effective method for identifying variants in protein-coding genes.
• While established in human medical genetics, WES is primarily a research tool in veterinary medicine.
• This study evaluates a WES design for potential clinical use in dogs.

Purpose of the Study:

• To assess the baseline performance characteristics of a WES design for veterinary clinical genetics.
• To determine the suitability of WES for identifying phenotype-associated variants in dogs.

Main Methods:

• 49 canine samples were analyzed using WES to detect 352 known phenotype-associated variants.
• Sequencing performance was compared for single nucleotide variants (SNVs) in exons, larger indels (≤20 bp) in exons, and intronic variants.
• Variant detection was assessed based on sequencing depth (≥10x).

Main Results:

• On average, 85% of exonic SNVs and 82% of larger exonic variants achieved ≥10x sequencing depth across 49 samples.
• Individual sample performance varied, with exonic SNV coverage ranging from 71% to 94% at ≥10x depth.
• The WES design showed efficacy in detecting variants within and outside the intended target regions.

Conclusions:

• This is the first report on the performance of a research-intended WES design for clinical veterinary genetics.
• WES demonstrated high efficacy in detecting variants, though performance varied by variant type and location.
• Future work should focus on developing improved WES designs and settings for veterinary clinical applications.