Abstract
BackgroundImproving resistance to mastitis, one of the costliest diseases in dairy production, has become an important objective in dairy cattle breeding. However, mastitis resistance is influenced by many genes involved in multiple processes, including the response to infection, inflammation, and post-infection healing. Low genetic heritability, environmental variations, and farm management differences further complicate the identification of links between genetic variants and mastitis resistance. Consequently, studies of the genetics of variation in mastitis resistance in dairy cattle lack agreement about the responsible genes.ResultsWe associated 15,552,968 imputed whole-genome sequencing markers for 5147 Nordic Holstein cattle with mastitis resistance in a genome-wide association study (GWAS). Next, we augmented P-values for markers in genes in the associated regions using Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and mammalian phenotype database. To confirm results of gene-based analyses, we used gene expression data from E. coli-challenged cow udders. We identified 22 independent quantitative trait loci (QTL) that collectively explained 14% of the variance in breeding values for resistance to clinical mastitis (CM). Using association test statistics with multiple pieces of independent information on gene function and differential expression during bacterial infection, we suggested putative causal genes with biological relevance for 12 QTL affecting resistance to CM in dairy cattle.ConclusionCombining information on the nearest positional genes, gene-based analyses, and differential gene expression data from RNA-seq, we identified putative causal genes (candidate genes with biological evidence) in QTL for mastitis resistance in Nordic Holstein cattle. The same strategy can be applied for other traits.
Highlights
Improving resistance to mastitis, one of the costliest diseases in dairy production, has become an important objective in dairy cattle breeding
According to Uniport [28], this gene encodes a protein involved in the N-glycan degradation pathway, but there is no known biological function relating this gene to mastitis resistance
The lead Single nucleotide polymorphism (SNP) on BTA19 was BTA19:43038655, located near STAT5A. Previous research proposed this gene as a candidate gene for cattle mastitis [31, 32]. This lead SNP was near BRCA1 (BTA19:43714457 ~ 43,783,351), which was previously proposed as a candidate gene for mastitis resistance [33]
Summary
One of the costliest diseases in dairy production, has become an important objective in dairy cattle breeding. Previous studies have identified quantitative trait loci (QTL) that are associated with variations in CM and its indicator trait, somatic cell count (SCC) [8,9,10,11]. These studies have proposed candidate genes, such as GC, NPFFR2 [12], TRAPPC, ARHGAP39 [13], LY6K, LY6D, LYNX1, LYPD2, SLURP1, and PSCA [14]. A gene-based association statistical approach accounts for the correlation structure among single-nucleotide polymorphisms (SNPs) within the gene and may have higher power to prioritize genes within an identified region to be candidates [15]. We expect that the causal gene will be enriched in trait-associated SNPs compared to neighboring genes
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