A Post-GWAS Replication Study Confirming the PTK2 Gene Associated with Milk Production Traits in Chinese Holstein

Abstract

Our initial genome-wide association study (GWAS) demonstrated that two SNPs (ARS-BFGL-NGS-33248, UA-IFASA-9288) within the protein tyrosine kinase 2 (PTK2) gene were significantly associated with milk production traits in Chinese Holstein dairy cattle. To further validate if the statistical evidence provided in GWAS were true-positive findings, a replication study was performed herein through genotype-phenotype associations. The two tested SNPs were found to show significant associations with milk production traits, which confirmed the associations observed in the original study. Specifically, SNPs lying in the PTK2 gene were also detected by sequencing 14 unrelated sires in Chinese Holsteins and a total of thirty-three novel SNPs were identified. Thirteen out of these identified SNPs were genotyped and tested for association with milk production traits in an independent resource population. After Bonferroni correction for multiple testing, twelve SNPs were statistically significant for more than two milk production traits. Analyses of pairwise D’ measures of linkage disequilibrium (LD) between all SNPs were also explored. Two haplotype blocks were inferred and the association study at haplotype level revealed similar effects on milk production traits. In addition, the RNA expression analyses revealed that a non-synonymous coding SNP (g.4061098T>G) was involved in the regulation of gene expression. Thus the findings presented here provide strong evidence for associations of PTK2 variants with dairy production traits and may be applied in Chinese Holstein breeding program.

Genetic Analyses Confirm SNPs in HSPA8 and ERBB2 are Associated with Milk Protein Concentration in Chinese Holstein Cattle

“…Generally, a small proportion with less than 1% of the phenotypic variance was explained by polymorphisms underlying complex traits in livestock animals [42]. In the present study, six and four significant pairs of SNP-trait explaining phenotypic variations with greater than 1% were found in HSPA8 and ERBB2 , respectively.…”

Genomic analyses for predicted milk fatty acid composition throughout lactation in North American Holstein cattle

“…Important contributions were found on BTA14. This chromosome is well known to have a substantial number of QTL for milk and fat production traits (Viitala et al, 2003;Wang et al, 2013), including DGAT1, a gene involved in the last step of the synthesis of triacylglycerol and that has a major effect on milk fat content (Grisart, 2002;Cruz et al, 2019). Despite its importance, DGAT1 was not found in this study because of the absence of markers located in its proximity.…”

Regulation of DNA methylation on EEF1D and RPL8 expression in cattle

“…Milk production traits are the most important traits in dairy cattle. In the past decades, many studies have been carried out to reveal the genetic basis of milk production traits (Zhang et al 1998 ; Farnir et al 2002 ; Ashwell et al 2004 ; Jiang et al 2010 ; Mai et al 2010 ) and a lot of candidate genes or QTL affecting milk yield and milk components have been reported (Viitala et al 2006 ; Winter et al 2002 ; Wang et al 2013 ). Along with the development of cost-effective “omics” technology, many powerful tools are being used to identify functional genes (mutations) and their regulatory mechanisms recently, such as genome-wide association studies (GWAS) (Jiang et al 2010 ; Mai et al 2010 ; Meredith et al 2012 ; Cole et al 2011 ) and gene expression profiles (Wickramasinghe et al 2012 ; Connor et al 2013 ; Singh et al 2013 ; Cui et al 2014 ).…”