Project description:Our initial RNA sequencing work identified that lipin 1 (LPIN1) was differentially expressed during dry period, early lactation, and peak of lactation in dairy cows, and it was enriched into the fat metabolic Gene Ontology (GO) terms and pathways, thus we considered LPIN1 as the candidate gene for milk production traits. In this study, we detected the polymorphisms of LPIN1 and verified their genetic effects on milk yield and composition in a Chinese Holstein cow population. We found seven SNPs by re-sequencing the entire coding region and partial flanking region of LPIN1, including one in 5' flanking region, four in exons, and two in 3' flanking region. Of these, four SNPs, c.637T > C, c.708A > G, c.1521C > T, and c.1555A > C, in the exons were predicted to result in the amino acid replacements. With the Haploview 4.2, we found that seven SNPs in LPIN1 formed two haplotype blocks (D' = 0.98-1.00). Single-SNP association analyses showed that SNPs were significantly associated with milk yield, fat yield, fat percentage, or protein yield in the first or second lactation (p = < 0.0001-0.0457), and only g.86049389C > T was strongly associated with protein percentage in both lactations (p = 0.0144 and 0.0237). The haplotype-based association analyses showed that the two haplotype blocks were significantly associated with milk yield, fat yield, protein yield, or protein percentage (p = < 0.0001-0.0383). By quantitative real-time PCR (qRT-PCR), we found that LPIN1 had relatively high expression in mammary gland and liver tissues. Furthermore, we predicted three SNPs, c.637T > C, c.708A > G, and c.1521C > T, using SOPMA software, changing the LPIN1 protein structure that might be potential functional mutations. In summary, we demonstrated the significant genetic effects of LPIN1 on milk production traits, and the identified SNPs could serve as genetic markers for dairy breeding.
Project description:Our initial RNA sequencing (RNA-seq) revealed that the Serum amyloid A1 (SAA1) gene was differentially expressed in the mammary glands of lactating Holstein cows with extremely high versus low phenotypic values of milk protein and fat percentage. To further validate the genetic effect and potential molecular mechanisms of SAA1 gene involved in regulating milk production traits in dairy cattle, we herein performed a study through genotype-phenotype associations. Six identified SNPs were significantly associated with one or more milk production traits (0.00002< P < 0.0025), providing additional evidence for the potential role of SAA1 variants in milk production traits in dairy cows. Subsequently, both luciferase assay and electrophoretic mobility shift assay (EMSA) clearly demonstrated that the allele A of g.-963C>A increased the promoter activity by binding the PARP factor while allele C did not. Bioinformatics analysis indicated that the secondary structure of SAA protein changed by the substitution A/G in the locus c. +2510A>G. Our findings were the first to reveal the significant associations of the SAA1 gene with milk production traits, providing basis for further biological function validation, and two identified SNPs, g.-963C>A and c. +2510A>G, may be considered as genetic markers for breeding in dairy cattle.
Project description:OBJECTIVE:This study was conducted to test the efficiency of genomic selection for milk production traits in a Korean Holstein cattle population. METHODS:A total of 506,481 milk production records from 293,855 animals (2,090 heads with single nucleotide polymorphism information) were used to estimate breeding value by single step best linear unbiased prediction. RESULTS:The heritability estimates for milk, fat, and protein yields in the first parity were 0.28, 0.26, and 0.23, respectively. As the parity increased, the heritability decreased for all milk production traits. The estimated generation intervals of sire for the production of bulls (LSB) and that for the production of cows (LSC) were 7.9 and 8.1 years, respectively, and the estimated generation intervals of dams for the production of bulls (LDB) and cows (LDC) were 4.9 and 4.2 years, respectively. In the overall data set, the reliability of genomic estimated breeding value (GEBV) increased by 9% on average over that of estimated breeding value (EBV), and increased by 7% in cows with test records, about 4% in bulls with progeny records, and 13% in heifers without test records. The difference in the reliability between GEBV and EBV was especially significant for the data from young bulls, i.e. 17% on average for milk (39% vs 22%), fat (39% vs 22%), and protein (37% vs 22%) yields, respectively. When selected for the milk yield using GEBV, the genetic gain increased about 7.1% over the gain with the EBV in the cows with test records, and by 2.9% in bulls with progeny records, while the genetic gain increased by about 24.2% in heifers without test records and by 35% in young bulls without progeny records. CONCLUSION:More genetic gains can be expected through the use of GEBV than EBV, and genomic selection was more effective in the selection of young bulls and heifers without test records.
Project description:The premises for the potential success of molecular breeding is the ability to identify major genes associated with important dairy related traits. The present study was taken up with the objectives to identify single nucleotide polymorphism (SNP) of bovine MASP2 and SIRT1 genes and its effect on estimated breeding values (EBVs) and to estimate genetic parameters for lactation milk yield (LMY), 305-day milk yield (305dMY), 305-day fat yield (305dFY), 305-day solid not fat yield (305dSNFY) and lactation length (LL) in Sahiwal dairy cattle to devise a promising improvement strategy. Genetic parameters and breeding values of milk production traits were estimated from 935 Sahiwal cattle population (1979-2019) reared at National Dairy Research Institute at Karnal, India. A total of 7 SNPs, where one SNP (g.499C>T) in exon 2 and four SNPs (g.576G>A, g.609T>C, g.684G>T and g.845A>G) in exon 3 region of MASP2 gene and 2 SNPs (g.-306T>C and g.-274G>C) in the promoter region of SIRT1 gene were identified in Sahiwal cattle population. Five of these identified SNPs were chosen for further genotyping by PCR-RFLP and association analysis. Association analysis was performed using estimated breeding values (n = 150) to test the effect of SNPs on LMY, 305dMY, 305dFY, 305dSNFY and LL. Association analysis revealed that, three SNP markers (g.499C>T, g.609T>C and g.-306T>C) were significantly associated with all milk yield traits. The estimates for heritability using repeatability model for LMY, 305dMY, 305dFY, 305dSNFY and LL were low, however the corresponding estimates from first parity were 0.20±0.08, 0.17±0.08, 0.13±0.09, 0.13±0.09 and 0.24, respectively. The repeatability estimates were moderate to high indicating consistency of performance over the parities and hence reliability of first lactation traits. Genetic correlations among the traits of first parity were high (0.55 to 0.99). From the results we could conclude that optimum strategy to improve the Sahiwal cattle further would be selecting the animals based on their first lactation 305dMY. Option top include the significant SNP in selection criteria can be explored. Taken together, a 2-stage selection approach, select Sahiwal animals early for the SNP and then on the basis of first lactation 305dMY will help to save resources.
Project description:BACKGROUND: Identification of the processes and mutations responsible for the large genetic variation in milk production among dairy cattle has proved challenging. One approach is to identify a biological process potentially involved in milk production and to determine the genetic influence of all the genes included in the process or pathway. Angiogenin encoded by angiogenin, ribonuclease, RNase A family 5 (RNASE5) is relatively abundant in milk, and has been shown to regulate protein synthesis and act as a growth factor in epithelial cells in vitro. However, little is known about the role of angiogenin in the mammary gland or if the polymorphisms present in the bovine RNASE5 gene are associated with lactation and milk production traits in dairy cattle. Given the high economic value of increased protein in milk, we have tested the hypothesis that RNASE5 or genes in the RNASE5 pathway are associated with milk production traits. First, we constructed a "RNASE5 pathway" based on upstream and downstream interacting genes reported in the literature. We then tested SNP in close proximity to the genes of this pathway for association with milk production traits in a large dairy cattle dataset. RESULTS: The constructed RNASE5 pathway consisted of 11 genes. Association analysis between SNP in 1 Mb regions surrounding these genes and milk production traits revealed that more SNP than expected by chance were associated with milk protein percent (P < 0.05 significance). There was no significant association with other traits such as milk fat content or fertility. CONCLUSIONS: These results support a role for the RNASE5 pathway in milk production, specifically milk protein percent, and indicate that polymorphisms in or near these genes explain a proportion of the variation for this trait. This method provides a novel way of understanding the underlying biology of lactation with implications for milk production and can be applied to any pathway or gene set to test whether they are responsible for the variation of complex traits.
Project description:BackgroundGenome-wide association studies (GWAS) are a powerful tool for detecting genomic regions explaining variation in phenotype. The objectives of the present study were to identify or refine the positions of genomic regions affecting milk production, milk components and fertility traits in Canadian Holstein cattle, and to use these positions to identify genes and pathways that may influence these traits.ResultSeveral QTL regions were detected for milk production (MILK), fat production (FAT), protein production (PROT) and fat and protein deviation (FATD, PROTD respectively). The identified QTL regions for production traits (including milk production) support previous findings and some overlap with genes with known relevant biological functions identified in earlier studies such as DGAT1 and CPSF1. A significant region on chromosome 21 overlapping with the gene FAM181A and not previous linked to fertility in dairy cattle was identified for the calving to first service interval and days open. A functional enrichment analysis of the GWAS results yielded GO terms consistent with the specific phenotypes tested, for example GO terms GO:0007595 (lactation) and GO:0043627 (response to estrogen) for milk production (MILK), GO:0051057 (positive regulation of small GTPase mediated signal transduction) for fat production (FAT), GO:0040019 (positive regulation of embryonic development) for first service to calving interval (CTFS) and GO:0043268 (positive regulation of potassium ion transport) for days open (DO). In other cases the connection between the enriched GO terms and the traits were less clear, for example GO:0003279 (cardiac septum development) for FAT and GO:0030903 (notochord development) for DO trait.ConclusionThe chromosomal regions and enriched pathways identified in this study confirm several previous findings and highlight new regions and pathways that may contribute to variation in production or fertility traits in dairy cattle.
Project description:BackgroundMilkability, primarily evaluated by measurements of milking speed and time, has an economic impact in milk production of dairy cattle. Recently the Italian Brown Swiss Breeders Association has included milking speed in genetic evaluations. The main objective of this study was to investigate the possibility of implementing genomic selection for milk flow traits in the Italian Brown Swiss population and thereby evaluate the potential of genomic selection for novel traits in medium-sized populations. Predicted breeding values and reliabilities based on genomic information were compared with those obtained from traditional breeding values.MethodsMilk flow measures for total milking time, ascending time, time of plateau, descending time, average milk flow and maximum milk flow were collected on 37 213 Italian Brown Swiss cows. Breeding values for genotyped sires (n = 1351) were obtained from standard BLUP and genome-enhanced breeding value techniques utilizing two-stage and single-step methods. Reliabilities from a validation dataset were estimated and used to compare accuracies obtained from parental averages with genome-enhanced predictions.ResultsGenome-enhanced breeding values evaluated using two-stage methods had similar reliabilities with values ranging from 0.34 to 0.49 for the different traits. Across two-stage methods, the average increase in reliability from parental average was approximately 0.17 for all traits, with the exception of descending time, for which reliability increased to 0.11. Combining genomic and pedigree information in a single-step produced the largest increases in reliability over parent averages: 0.20, 0.24, 0.21, 0.14, 0.20 and 0.21 for total milking time, ascending time, time of plateau, descending time, average milk flow and maximum milk flow, respectively.ConclusionsUsing genomic models increased the accuracy of prediction compared to traditional BLUP methods. Our results show that, among the methods used to predict genome-enhanced breeding values, the single-step method was the most successful at increasing the reliability for most traits. The single-step method takes advantage of all the data available, including phenotypes from non-genotyped animals, and can easily be incorporated into current breeding evaluations.
Project description:The estimation of dominance effects requires the availability of direct phenotypes, i.e., genotypes and phenotypes in the same individuals. In dairy cattle, classical QTL mapping approaches are, however, relying on genotyped sires and daughter-based phenotypes like breeding values. Thus, dominance effects cannot be estimated. The number of dairy bulls genotyped for dense genome-wide marker panels is steadily increasing in the context of genomic selection schemes. The availability of genotyped cows is, however, limited. Within the current study, the genotypes of male ancestors were applied to the calculation of genotype probabilities in cows. Together with the cows' phenotypes, these probabilities were used to estimate dominance effects on a genome-wide scale. The impact of sample size, the depth of pedigree used in deriving genotype probabilities, the linkage disequilibrium between QTL and marker, the fraction of variance explained by the QTL, and the degree of dominance on the power to detect dominance were analyzed in simulation studies. The effect of relatedness among animals on the specificity of detection was addressed. Furthermore, the approach was applied to a real data set comprising 470,000 Holstein cows. To account for relatedness between animals a mixed-model two-step approach was used to adjust phenotypes based on an additive genetic relationship matrix. Thereby, considerable dominance effects were identified for important milk production traits. The approach might serve as a powerful tool to dissect the genetic architecture of performance and functional traits in dairy cattle.
Project description:The Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway genes along with suppressors of cytokine signalling (SOCS) family genes play a crucial role in controlling cytokine signals in the mammary gland and thus mammary gland development. Mammary gene expression studies showed differential expression patterns for all the JAK-STAT pathway genes. Gene expression studies using qRT-PCR revealed differential expression of SOCS2, SOCS4, and SOCS5 genes across the lactation cycle in dairy cows. Using genotypes from 1,546 Australian Holstein-Friesian bulls, a statistical model for an association analysis based on SNPs within 500 kb of JAK-STAT pathway genes, and SOCS genes alone was constructed. The analysis suggested that these genes and pathways make a significant contribution to the Australian milk production traits. There were 24 SNPs close to SOCS1, SOCS3, SOCS5, SOCS7, and CISH genes that were significantly associated with Australian Profit Ranking (APR), Australian Selection Index (ASI), and protein yield (PY). This study supports the view that there may be some merit in choosing SNPs around functionally relevant genes for the selection and genetic improvement schemes for dairy production traits.