Unidad de Genética y Mejora Animal, Departamento de Producción Animal, Facultad de Veterinaria, Universidad de la República, Montevideo 11600, Uruguay.
Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
J Anim Sci. 2022 May 1;100(5). doi: 10.1093/jas/skac110.
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.
眼部鳞状细胞癌和传染性角膜结膜炎是 Hereford 牛常见的眼部疾病，具有相当大的经济影响。这两种疾病都与下眼睑色素沉着减少有关，因此，通过遗传选择提高上眼睑色素沉着可以降低其发病率。本研究的目的是揭示 Hereford 牛眼睑色素沉着的遗传基础。分析包括单步全基因组关联研究（ssGWAS）和随后的基因集分析，以确定与该性状相关的个体基因、遗传机制和生物学途径。数据包括 1165 头 Hereford 公牛和阉牛的眼睑色素沉着记录，在 0%到 100%之间分为五个等级进行视觉评估。有色素沉着记录的 886 只动物的 774660 个单核苷酸多态性标记的基因型数据可用。本研究考虑了动物表型三代祖先的系谱信息，共有 4929 只动物。我们的分析表明，眼睑色素沉着是一种中度可遗传的性状，遗传力估计值约为 0.41。ssGWAS 确定了至少 8 个位于 BTA1、BTA3、BTA5、BTA14、BTA16、BTA18、BTA19 和 BTA24 上的区域与眼睑色素沉着有关。这些区域包含直接参与黑素细胞生物学和皮肤色素沉着的基因，如 ADCY8、PLD1、KITLG 和 PRKCA。基因集分析揭示了几个与黑素生成密切相关的功能术语，如黑素细胞分化的正调控和 ERK1 和 ERK2 级联的调控。总的来说，我们的研究结果表明，眼睑色素沉着是一种受许多基因影响的可遗传性状。事实上，ssGWAS 检测到了几个直接参与黑素细胞生物学的候选基因，包括黑素生成。本研究有助于更好地理解眼睑色素沉着的遗传和生物学基础，并提供了新的信息，可用于设计减少牛眼部疾病发病率的育种策略。需要进一步研究眼睑色素沉着与眼部疾病之间的遗传联系。
