Companion animals

Genetic Analysis of Labrador Retriever Primary Ciliary Dyskinesia Using Genome-Wide Association and Sequencing

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Abstract

The objective of this study was to elucidate the genetic basis of canine primary ciliary dyskinesia (PCD) in Labrador Retrievers and Labrador à— Golden Retriever crosses from a guide dog breeding program. The dataset comprised of 20 clinically confirmed PCD cases and 1,400 unaffected controls. Genotypes were imputed and pruned for linkage disequilibrium, resulting in a final dataset of 438,480 SNPs. To address the extreme case-control imbalance and high relatedness among samples, genome-wide association analysis (GWAS) was conducted using a generalized linear mixed model (GLMM) with saddlepoint approximation implemented in SAIGE which is optimized to handle unbalanced datasets and cryptic relatedness while preserving statistical power and controlling for type I error. A significant association (Bonferroni P < 0.05) was identified on an 8.8 Mb (0.22 - 9.02 Mb) region on chromosome 2 containing several genes implicated in ciliary function, including SPAG6, MYO3A, ARMC3, MEIG1, ENKUR, and ITGB1. 156 SNPs reached genome wide significance, with the lead SNP at 2:3565037 (-log10 P = 7.49) Runs of homozygosity analysis revealed 100% homozygosity across the region in all cases, supporting a recessive founder mutation. Whole-genome sequencing of 24 dogs, including 5 cases, identified 156 homozygous recessive variants; 155 of which were within the GWAS significance region, all exhibiting perfect segregation in cases and in complete linkage. Of these, only two were protein altering: a missense variant and a frame-shift mutation in SPAG6. RNA sequencing of 12 dogs, including 4 cases, revealed that MYO3A was the only gene in the region significantly upregulated in the cases. However further analysis showed allele specific expression of SPAG6 in cases and allelic imbalance in carriers, suggesting RNA instability of the SPAG6 transcript. These results establish a specific genomic locus for PCD in Labrador Retrievers, providing a basis for genetic screening and further understanding of the molecular mechanisms of ciliopathies.

Keywords: 2026

How to Cite:

Srikanth, K., Thorsrud, J., Quigley, K., Evans, K. & Huson, H., (2026) “Genetic Analysis of Labrador Retriever Primary Ciliary Dyskinesia Using Genome-Wide Association and Sequencing”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2287295. doi: https://doi.org/10.31274/wcgalp.24258

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