After genome-wide association studies: Gene networks elucidating candidate genes divergences for number of teats across two pig populations.

Number of teats (NT) is an important trait affecting both piglet's welfare and the production level of pig farms. Biologically, embryonic mammary gland development requires the coordination of many signaling pathways necessary for the proper development of teats. Several QTL for NT have been identified; however, further analysis is still lacking. Therefore, gene networks derived from genomewide association study (GWAS) results can be used to examine shared pathways and functions of putative candidate genes. Besides, such analyses may also be helpful to understand the genetic diversity between populations for the same trait or traits. In this study, we identified significant SNP for Landrace-based (line C) and Large White-based (line D) dam lines. Besides, gene-transcription factor (TF) networks were constructed aiming to obtain the most likely candidate genes for NT in each line followed by a comparative analysis between both lines to access similarities or dissimilarities at the marker and gene level. We identified 24 and 19 significant SNP (Bayes factor ≥ 100) for lines C and D, respectively. Only 1 significant SNP overlapped both lines. Network analysis illustrated gene interactions consistent with known mammal's breast biology and captured known TF. We observed different sets of putative candidate genes for NT in each line evaluated that may have common effects on the phenotype. Based on these results, we demonstrated the importance of post-GWAS analyses increasing the biological understanding of relevant genes for a complex trait. Moreover, we believe that this genomic diversity across lines should be taken into account, considering breed-specific reference populations for genomic selection.

Genetic parameters for natural antibody isotype titers in milk of Dutch Holstein-Friesians.

The objective of the present study was to estimate genetic parameters for natural antibody isotypes immunoglobulin (Ig) A, IgG1 and IgM titers binding the bacterial antigens lipopolysaccharide, peptidoglycan and the model antigen keyhole limpet hemocyanin in Dutch Holstein-Friesian cows (n = 1695). Further, this study included total natural antibody titers binding the antigens mentioned above, making no isotype distinction, as well as total natural antibody titers and natural antibody isotypes IgA, IgG1 and IgM binding lipoteichoic acid. The study showed that natural antibody isotype titers are heritable, ranging from 0.06 to 0.55, and that these heritabilities were generally higher than heritabilities for total natural antibody titers. Genetic correlations, the combinations of total natural antibody titers and natural antibody isotype titers, were nearly all positive and ranged from -0.23 to 0.99. Strong genetic correlations were found between IgA and IgM. Genetic correlations were substantially weaker when they involved an IgG1 titer, indicating that IgA and IgM have a common genetic basis, but that the genetic basis for IgG1 differs from that for IgA or IgM. Results from this study indicate that natural antibody isotype titers show the potential for effective genetic selection. Further, natural antibody isotypes may provide a better characterization of different elements of the immune response or immune competence. As such, natural antibody isotypes may enable more effective decisions when breeding programs start to include innate immune parameters.

Genome-wide associations for fertility traits in Holstein-Friesian dairy cows using data from experimental research herds in four European countries.

Genome-wide association studies for difficult-to-measure traits are generally limited by the sample population size with accurate phenotypic data. The objective of this study was to utilise data on primiparous Holstein-Friesian cows from experimental farms in Ireland, the United Kingdom, the Netherlands and Sweden to identify genomic regions associated with traditional measures of fertility, as well as a fertility phenotype derived from milk progesterone profiles. Traditional fertility measures investigated were days to first heat, days to first service, pregnancy rate to first service, number of services and calving interval (CI); post-partum interval to the commencement of luteal activity (CLA) was derived using routine milk progesterone assays. Phenotypic and genotypic data on 37 590 single nucleotide polymorphisms (SNPs) were available for up to 1570 primiparous cows. Genetic parameters were estimated using linear animal models, and univariate and bivariate genome-wide association analyses were undertaken using Bayesian stochastic search variable selection performed using Gibbs sampling. Heritability estimates of the traditional fertility traits varied from 0.03 to 0.16; the heritability for CLA was 0.13. The posterior quantitative trait locus (QTL) probabilities, across the genome, for the traditional fertility measures were all <0.021. Posterior QTL probabilities of 0.060 and 0.045 were observed for CLA on SNPs each on chromosome 2 and chromosome 21, respectively, in the univariate analyses; these probabilities increased when CLA was included in the bivariate analyses with the traditional fertility traits. For example, in the bivariate analysis with CI, the posterior QTL probability of the two aforementioned SNPs were 0.662 and 0.123. Candidate genes in the vicinity of these SNPs are discussed. The results from this study suggest that the power of genome-wide association studies in cattle may be increased by sharing of data and also possibly by using physiological measures of the trait under investigation.

Genomic associations with somatic cell score in first-lactation Holstein cows.

This genome-wide association study aimed to identify loci associated with lactation-average somatic cell score (LASCS) and the standard deviation of test-day somatic cell score (SCS-SD). It is one of the first studies to combine detailed phenotypic and genotypic cow data from research dairy herds located in different countries. The combined data set contained up to 52 individual test-days per lactation and thereby aimed to capture temporary increases in somatic cell score associated with infection. Phenotypic data for analysis consisted of 46,882 test-day records on 1,484 cows, and genotypic data consisted of 37,590 single nucleotide polymorphisms (SNP). Using an animal model, the associations between each individual SNP and the phenotypic data were estimated. To account for the risk of false positives, a false discovery rate threshold of 0.20 was set. The analyses showed that LASCS was significantly associated with a SNP on Bos taurus autosome (BTA) 4 and a SNP on BTA18. Likewise, SCS-SD was associated with this SNP on BTA18. In addition, SCS-SD significantly associated with a SNP on BTA6. Relatively few associations were found, suggesting that LASCS and SCS-SD are controlled by multiple loci distributed across the genome, each with a relatively small effect. Increased knowledge on genetic regulation of LASCS and SCS-SD may aid in identification of genes that play a role in mastitis resistance. Such knowledge helps us understand the genetic mechanisms leading to mastitis and in discovery of targets for mastitis therapeutics.

Genetic variation of natural antibodies in milk of Dutch Holstein-Friesian cows.

Defense mechanisms of dairy cows against diseases partly rest on their naturally present disease resistance capacity. Natural antibodies (NAb) form a soluble part of the innate immune system, being defined as antibodies circulating in animals without prior intentional antigenic stimulation. Genetic selection on NAb titers in milk, therefore, might improve disease resistance. We estimated genetic parameters of NAb titers binding lipopolysaccharide, lipoteichoic acid (LTA), peptidoglycan, and keyhole limpet hemocyanin, and titers of the NAb isotypes IgG1, IgM, and IgA binding LTA in milk of Dutch Holstein-Friesian heifers. Natural antibody titers were measured in 1 milk sample from each of 1,939 Holstein-Friesian heifers and used for estimating genetic parameters of NAb titers. The data show that phenotypic variation exists among heifers in NAb titers binding lipopolysaccharide, LTA, peptidoglycan, and keyhole limpet hemocyanin, and the NAb isotypes IgG1, IgM, and IgA binding LTA in milk. High genetic correlations among NAb (ranging from 0.45 to 0.99) indicated a common genetic basis for the levels of different NAb in bovine milk. Intra-herd heritability estimates for NAb ranged from 0.10 to 0.53. The results indicated that NAb levels have potential for genetic selection.

Genetic parameters for levels of natural antibodies in chicken lines divergently selected for specific antibody response.

The present study estimated the heritability of natural antibody (NAb) levels binding rabbit red blood cells at the day of immunization with SRBC (NAb0) and 5 d postimmunization (NAb5) in 2 chicken lines divergently selected for specific antibody levels (SpAb) against SRBC and a randombred control line. In addition, genetic correlations between the levels of NAb binding rabbit red blood cells and levels of SpAb binding SRBC were estimated. The heritability of the SpAb level against SRBC was estimated based on data from 23 generations of selection and in total 21,842 chickens. The heritability of NAb levels against rabbit red blood cells was estimated on 1,764 chickens in generations 22 and 23 using a bivariate analysis including the trait under selection (i.e., SpAb responses to SRBC). Maternal environmental effects were accounted for in the analyses. The heritability for SpAb was 0.17, the heritability for NAb0 levels was 0.23, and the heritability for NAb5 was 0.09. The genetic correlation between SpAb and NAb0 was 0.15 and the genetic correlation between SpAb and NAb5 was 0.50. The weak, though positive, genetic correlation between SpAb responses and the NAb0 levels in nonimmunized chickens, as well as the moderate genetic correlation between SpAb responses and the NAb levels 5 d postimmunization with SRBC, suggest that selection for enhanced adaptive immune system results in a positive correlated response of the innate immunity of chickens.