A better understanding of the genetic architecture of complex traits can contribute to improve genomic prediction. We hypothesized that genomic variants associated with mastitis and milk production traits in dairy cattle are enriched in hepatic transcriptomic regions that are responsive to intra-mammary infection (IMI). Genomic markers [e.g. single nucleotide polymorphisms (SNPs)] from those regions, if included, may improve the predictive ability of a genomic model. We applied a genomic feature best linear unbiased prediction model (GFBLUP) to implement the above strategy by considering the hepatic transcriptomic regions responsive to IMI as genomic features. GFBLUP, an extension of GBLUP, includes a separate genomic effect of SNPs within a genomic feature, and allows differential weighting of the individual marker relationships in the prediction equation. Since GFBLUP is computationally intensive, we investigated whether a SNP set test could be a computationally fast way to preselect predictive genomic features. The SNP set test assesses the association between a genomic feature and a trait based on single-SNP genome-wide association studies. We applied these two approaches to mastitis and milk production traits (milk, fat and protein yield) in Holstein (HOL, n = 5056) and Jersey (JER, n = 1231) cattle. We observed that a majority of genomic features were enriched in genomic variants that were associated with mastitis and milk production traits. Compared to GBLUP, the accuracy of genomic prediction with GFBLUP was marginally improved (3.2 to 3.9%) in within-breed prediction. The highest increase (164.4%) in prediction accuracy was observed in across-breed prediction. The significance of genomic features based on the SNP set test were correlated with changes in prediction accuracy of GFBLUP (P < 0.05). GFBLUP provides a framework for integrating multiple layers of biological knowledge to provide novel insights into the biological basis of complex traits, and to improve the accuracy of genomic prediction. The SNP set test might be used as a first-step to improve GFBLUP models. Approaches like GFBLUP and SNP set test will become increasingly useful, as the functional annotations of genomes keep accumulating for a range of species and traits.

A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic regions defined by genes grouped on the basis of “Gene Ontology” (GO), and that incorporating this independent biological information into genomic prediction models might improve their predictive ability. Four complex traits (i.e., milk, fat and protein yields, and mastitis) together with imputed sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased prediction model (GBLUP) to a genomic feature BLUP (GFBLUP) model, including an additional genomic effect quantifying the joint effect of a group of variants located in a genomic feature. The GBLUP model using a single random effect assumes that all genomic variants contribute to the genomic relationship equally, whereas GFBLUP attributes different weights to the individual genomic relationships in the prediction equation based on the estimated genomic parameters. Our results demonstrate that the immune-relevant GO terms were more associated with mastitis than milk production, and several biologically meaningful GO terms improved the prediction accuracy with GFBLUP for the four traits, as compared with GBLUP. The improvement of the genomic prediction between breeds (the average increase across the four traits was 0.161) was more apparent than that it was within the HOL (the average increase across the four traits was 0.020). Our genomic feature modelling approaches provide a framework to simultaneously explore the genetic architecture and genomic prediction of complex traits by taking advantage of independent biological knowledge.

Background: Over several decades, a wide range of natural and artificial selection events in response to subtropical environments, intensive pasture and intensive feedlot systems have greatly changed the customary behaviour, appearance, and important economic traits of Shanghai Holstein cattle. In particular, the longevity of the Shanghai Holstein cattle population is generally short, approximately the 2nd to 3rd lactation. In this study, two complementary approaches, integrated haplotype score (iHS) and runs of homozygosity (ROH), were applied for the detection of selection signatures within the genome using genotyping by genome-reduced sequence data from 1092 cows. Results: In total, 101 significant iHS genomic regions containing selection signatures encompassing a total of 256 candidate genes were detected. There were 27 significant |iHS| genomic regions with a mean |iHS| score > 2. The average number of ROH per individual was 42.15 ± 25.47, with an average size of 2.95 Mb. The length of 78 % of the detected ROH was within the range of 1–2 MB and 2–4 MB, and 99 % were shorter than 8 Mb. A total of 168 genes were detected in 18 ROH islands (top 1 %) across 16 autosomes, in which each SNP showed a percentage of occurrence > 30 %. There were 160 and 167 genes associated with the 52 candidate regions within health-related QTL intervals and 59 candidate regions within reproduction-related QTL intervals, respectively. Annotation of the regions harbouring clustered |iHS| signals and candidate regions for ROH revealed a panel of interesting candidate genes associated with adaptation and economic traits, such as IL22RA1, CALHM3, ITGA9, NDUFB3, RGS3, SOD2, SNRPA1, ST3GAL4, ALAD, EXOSC10, and MASP2. In a further step, a total of 1472 SNPs in 256 genes were matched with 352 cis-eQTLs in 21 tissues and 27 trans-eQTLs in 6 tissues. For SNPs located in candidate regions for ROH, a total of 108 cis-eQTLs in 13 tissues and 4 trans-eQTLs were found for 1092 SNPs. Eighty-one eGenes were significantly expressed in at least one tissue relevant to a trait (P value < 0.05) and matched the 256 genes detected by iHS. For the 168 significant genes detected by ROH, 47 gene-tissue pairs were significantly associated with at least one of the 37 traits. Conclusions: We provide a comprehensive overview of selection signatures in Shanghai Holstein cattle genomes by combining iHS and ROH. Our study provides a list of genes associated with immunity, reproduction and adaptation. For functional annotation, the cGTEx resource was used to interpret SNP-trait associations. The results may facilitate the identification of genes relevant to important economic traits and can help us better understand the biological processes and mechanisms affected by strong ongoing natural or artificial selection in livestock populations.

Information about genetic parameters is population specific and it is crucial for designing animal breeding programs and predicting response to selection. This study was carried out to estimate the genetic parameters for 23 body conformation traits of 45,517 Chinese Holstein reared in Eastern China from 1995 to 2017 with the Bayesian inference method using a linear animal mixed model. The methods to integrate these traits included (1) using the composite index from the Dairy Association of China and (2) applying principal component analysis and factor analysis to explore the relationship between the conformation traits. Estimates of heritability using the composite index were low (0.04; feet and legs) to moderate (0.23; body capacity). Strong genetic correlations were observed between the individual body conformation traits. Both principal components (1 to 7; eigenvalues ≥ 1) and latent factors (1 to 7; eigenvalues ≥ 1) explained 60.37% of total variability. Principal component 1 and factor 1 accounted for the traits that are usually associated with milk production. Moderate to low heritability were estimated through multi-trait analysis for principal components (from 0.07 to 0.21) and latent factors (from 0.07 to 0.23). Genetic correlations among the 2 multivariate techniques are typically lower compared with the one existing among the measured traits. Results from these analyses suggest the possibility of using both principal component analysis and factor analysis in morphological evaluation, simplifying the information given by the body conformation traits into new variables that could be useful for the genetic improvement of the Chinese Holstein population. This information could also be used to avoid analyzing large number of correlated traits, thereby improving precision and reducing computation burdens to analyze large and complex data.

The aim of this study was to investigate the genetic parameters and genetic architectures of six milk production traits in the Shanghai Holstein population. The data used to estimate the genetic parameters consisted of 1,968,589 test-day records for 305,031 primiparous cows. Among the cows with phenotypes, 3,016 cows were genotyped with Illumina Bovine SNP50K BeadChip, GeneSeek Bovine 50K BeadChip, GeneSeek Bovine LD BeadChip v4, GeneSeek Bovine 150K BeadChip, or low-depth whole-genome sequencing. A genome-wide association study was performed to identify quantitative trait loci and genes associated with milk production traits in the Shanghai Holstein population using genotypes imputed to whole-genome sequences and both fixed and random model circulating probability unification and a mixed linear model with rMVP software. Estimated heritabilities (h2) varied from 0.04 to 0.14 for somatic cell score (SCS), 0.07 to 0.22 for fat percentage (FP), 0.09 to 0.27 for milk yield (MY), 0.06 to 0.23 for fat yield (FY), 0.09 to 0.26 for protein yield (PY), and 0.07 to 0.35 for protein percentage (PP), respectively. Within lactation, genetic correlations for SCS, FP, MY, FY, PY, and PP at different stages of lactation estimated in random regression model were ranged from -0.02 to 0.99, 0.18 to 0.99, 0.04 to 0.99, 0.04 to 0.99, 0.01 to 0.99, and 0.33 to 0.99, respectively. The genetic correlations were highest between adjacent DIM but decreased as DIM got further apart. Candidate genes included those related to production traits (DGAT1, MGST1, PTK2, and SCRIB), disease-related (LY6K, COL22A1, TECPR2, and PLCB1), heat stress–related (ITGA9, NDST4, TECPR2, and HSF1), and reproduction-related (7SK and DOCK2) genes. This study has shown that there are differences in the genetic mechanisms of milk production traits at different stages of lactation. Therefore, it is necessary to conduct research on milk production traits at different stages of lactation as different traits. Our results can also provide a theoretical basis for subsequent molecular breeding, especially for the novel genetic loci.

Introduction:Chinese Holstein in South China suffer heat stress for a long period, which leads to evolutionary differences from Chinese Holstein in North China. The aim of this study was to estimate the genetic parameters of fertility traits for Chinese Holstein in South China.Methods:A total of 167,840 Chinese Holstein heifers and cows from Guangming Animal Husbandry Co., LTD farms were used in this study. The fertility traits analyzed were calving interval (CI), days open (DO), age of first service (AFS), age of first calving (AFC), calving to first insemination (CTFS), first insemination to conception (FSTC), gestation length (GL), non-return rate to 56 days (NRR), and number of services (NS).Results:The descriptive statistics revealed that the same trait in heifers performed better than in cows, which was consistent with the other studies. The heritabilities of fertility traits in this study ranged from close to 0 (for NS of cows) to 0.2474 (for AFC of heifers). The genetic correlation of NRR between heifers and cows was 0.9993, which indicates that the NRR for heifers and cows could be treated as one trait in this population.Conclusion:The heritabilities of fertility traits in Chinese Holstein in south China were quite different from the heritabilities of fertility traits in North China. NRR56, NS, AFC, and CI were suggested to be included into the selection index to improve fertility performance of Chinsese Holstein of south China. The results of this study could provide genetic parameters for the animal breeding program of Chinese Holstein in the south of China.