Identifying Genetic Predisposition to Dozer Lamb Syndrome: A Semi-Lethal Muscle Weakness Disease in Sheep.

Abstract

Background: Lamb health is crucial for producers; however, the percentage of lambs that die before weaning is still 15-20%. One factor that can contribute to lamb deaths is congenital diseases. A novel semi-lethal disease has been identified in newborn Polypay lambs and termed dozer lamb syndrome. This study aims to determine if there is a genetic predisposition to dozer lamb syndrome. These lambs are weak and unable to lift their heads, suckle, and swallow, resulting in nasal reflux.

Methods: Genetic analyses, including a genome-wide association, runs of homozygosity, and fine mapping to determine haploblock within regions of interest, were utilized in determining genetic predispositions to dozer lamb syndrome.

Results: The genome-wide association study identified a region of chromosome 15 with three significant SNPs (p-values of 6.81 × 10^-6, 5.71 × 10^-6, and 8.52 × 10^-6). Genetic analysis identified a run of homozygosity on the same region of chromosome 15 with an odds ratio of 236.7. Fine mapping of this region identified three haploblocks associated with the dozer lamb syndrome (p-value = 2.41 × 10^-5).

Conclusions: The most significant and promising gene in this region is CELF1, which is known to play an important role in muscle development. Abnormal CELF1 abundance and cellular location are reported to result in abnormal muscle development. Identification of genetic aberrations associated with dozer lamb syndrome provides a tool for decreasing or eliminating the genotype and, thus, the associated phenotype(s) from Polypay sheep.