Ocular squamous cell carcinoma and infectious keratoconjunctivitis are common ocular pathologies in Hereford cattle with considerable economic impact. Both pathologies have been associated with low eyelid pigmentation, and thus, genetic selection for higher eyelid pigmentation could reduce their incidence. The objective of the present study was to reveal the genetic basis of eyelid pigmentation in Hereford cattle. The analysis included a single-step genome-wide association study (ssGWAS) and a subsequent gene-set analysis in order to identify individual genes, genetic mechanisms, and biological pathways implicated in this trait. Data consisted of eyelid pigmentation records in 1,165 Hereford bulls and steers, visually assessed in five categories between 0% and 100%. Genotypic data for 774,660 single-nucleotide polymorphism markers were available for 886 animals with pigmentation records. Pedigree information of three generations of ancestors of animals with phenotype was considered in this study, with a total of 4,929 animals. Our analyses revealed that eyelid pigmentation is a moderately heritable trait, with heritability estimates around 0.41. The ssGWAS identified at least eight regions, located on BTA1, BTA3, BTA5, BTA14, BTA16, BTA18, BTA19, and BTA24, associated with eyelid pigmentation. These regions harbor genes that are directly implicated in melanocyte biology and skin pigmentation, such as ADCY8, PLD1, KITLG, and PRKCA. The gene-set analysis revealed several functional terms closely related to melanogenesis, such as positive regulation of melanocyte differentiation and regulation of ERK1 and ERK2 cascade. Overall, our findings provide evidence that eyelid pigmentation is a heritable trait influenced by many loci. Indeed, the ssGWAS detected several candidate genes that are directly implicated in melanocyte biology, including melanogenesis. This study contributes to a better understanding of the genetic and biological basis of eyelid pigmentation and presents novel information that could aid to design breeding strategies for reducing the incidence of ocular pathologies in cattle. Additional research on the genetic link between eyelid pigmentation and ocular pathologies is needed.
Keywords: beef cattle; melanocyte biology; ocular pathologies.
Low eyelid pigmentation is considered as a predisposing factor associated with common ocular pathologies in cattle, such as ocular squamous cell carcinoma and infectious keratoconjunctivitis, with considerable economic impact. The aim of our study was to investigate the genetic basis of eyelid pigmentation in Hereford cattle. The analysis included estimation of genetic parameters, a genome-wide association study, and a subsequent gene-set analysis to identify individual genes, genetic mechanisms, and biological pathways implicated in eyelid pigmentation. Our results indicate that eyelid pigmentation is a complex trait, with a moderate heritability around 0.41, and affected by multiple loci, including genes related to melanocyte biology, melanogenesis, skin pigmentation, and development of melanoma. Evidence that biological processes such as melanocyte development and melanocyte differentiation explain part of the observed variation in eyelid pigmentation were also found. Overall, this study provides a better understanding of the genetics underlying eyelid pigmentation in Hereford. Our findings could contribute to point out breeding strategies for reducing the incidence of ocular pathologies in cattle.
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