Searching new signals for production traits through gene-based association analysis in three Italian cattle breeds

Abstract

Genome-wide association studies (GWAS) have been widely applied to disentangle the genetic basis of complex traits. In cattle breeds, classical GWAS approaches with medium-density marker panels are far from conclusive, especially for complex traits. This is due to the intrinsic limitations of GWAS and the assumptions that are made to step from the association signals to the functional variations. Here, we applied a gene-based strategy to prioritize genotype-phenotype associations found for milk production and quality traits with classical approaches in three Italian dairy cattle breeds with different sample sizes (Italian Brown n = 745; Italian Holstein n = 2058; Italian Simmental n = 477). Although classical regression on single markers revealed only a single genome-wide significant genotype-phenotype association, for Italian Holstein, the gene-based approach identified specific genes in each breed that are associated with milk physiology and mammary gland development. As no standard method has yet been established to step from variation to functional units (i.e., genes), the strategy proposed here may contribute to revealing new genes that play significant roles in complex traits, such as those investigated here, amplifying low association signals using a gene-centric approach.

Genome-wide detection of copy-number variations in local cattle breeds

“…The SERPIND1 gene in mammals plays a crucial role in the control of the endopeptidases that mediate important pathways, such as blood coagulation, fibrinolysis, inflammation and complement activation (Rau et al 2007;Silverman et al 2001), some of which are considered the host's first line of defence to hematophagous and blood-dwelling parasites. The POU1F1 gene encodes a protein reportedly involved in productive life (Huang et al 2008), whereas PTK2 , FOXF2 (Capomaccio et al 2015) and LAMB3 (Gutiérrez-Gil et al 2015) reportedly encode proteins associated with milk production traits. ZBTB20 is a gene that overlaps the bovine QTL regions associated with milk traits and encodes a transcription factor that has been implicated in hematopoiesis, oncogenesis and the immune response in mammals (dos Santos et al 2017).…”

Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays

“…The classical GWAS approach aims to identify genomic regions associated with the investigated trait (QTL), but it is limited by the nature of the SNP information considered [i.e., known investigated variants (tag-SNP) are associated with unknown causative SNP, but the link with possible functional units (genes) is lost (Capomaccio et al, 2015a)]. To improve the usability of the results and enhance low-signal catching, various strategies can be applied.…”

Proliferation and apoptosis in subcutaneous adipose tissue of lactating cows with different genetic merit for milk yield

“…** = P < 0.01. higher performances, which are preferentially used for reproduction purposes. Genotype to phenotype genome wide association studies have demonstrated that selecting for EBV leads to a significant changes of the frequency of DNA variants in the progenies, most of them in the regulatory or coding sequence of genome (Capomaccio et al, 2015). Recently, it has also been reported that the variable genetic merit for milk yield can influence the expression of genes also involved in fat metabolism and can produce specific molecular signature (Sandri et al, 2015).…”