Francesco Tiezzi

A Genome-Wide Association Study for Clinical Mastitis in First Parity US Holstein Cows Using Single-Step Approach and Genomic Matrix Re-Weighting Procedure

Clinical mastitis (CM) is one of the health disorders with large impacts on dairy farming profitability and animal welfare. The objective of this study was to perform a genome-wide association study (GWAS) for CM in first-lactation Holstein. Producer-recorded mastitis event information for 103,585 first-lactation cows were used, together with genotype information on 1,361 bulls from the Illumina BovineSNP50 BeadChip. Single-step genomic-BLUP methodology was used to incorporate genomic data into a threshold-liability model. Association analysis confirmed that CM follows a highly polygenic mode of inheritance. However, 10-adjacent-SNP windows showed that regions on chromosomes 2, 14 and 20 have impacts on genetic variation for CM. Some of the genes located on chromosome 14 (LY6K, LY6D, LYNX1, LYPD2, SLURP1, PSCA) are part of the lymphocyte-antigen-6 complex (LY6) known for its neutrophil regulation function linked to the major histocompatibility complex. Other genes on chromosome 2 were also involved in regulating immune response (IFIH1, LY75, and DPP4), or are themselves regulated in the presence of specific pathogens (ITGB6, NR4A2). Other genes annotated on chromosome 20 are involved in mammary gland metabolism (GHR, OXCT1), antibody production and phagocytosis of bacterial cells (C6, C7, C9, C1QTNF3), tumor suppression (DAB2), involution of mammary epithelium (OSMR) and cytokine regulation (PRLR). DAVID enrichment analysis revealed 5 KEGG pathways. The JAK-STAT signaling pathway (cell proliferation and apoptosis) and the ‘Cytokine-cytokine receptor interaction’ (cytokine and interleukines response to infectious agents) are co-regulated and linked to the ‘ABC transporters’ pathway also found here. Gene network analysis performed using GeneMania revealed a co-expression network where 665 interactions existed among 145 of the genes reported above. Clinical mastitis is a complex trait and the different genes regulating immune response are known to be pathogen-specific. Despite the lack of information in this study, candidate QTL for CM were identified in the US Holstein population.

Accounting for trait architecture in genomic predictions of US Holstein cattle using a weighted realized relationship matrix

BackgroundGenomic BLUP (GBLUP) can predict breeding values for non-phenotyped individuals based on the identity-by-state genomic relationship matrix (G). The G matrix can be constructed from thousands of markers spread across the genome. The strongest assumption of G and consequently of GBLUP is that all markers contribute equally to the genetic variance of a trait. This assumption is violated for traits that are controlled by a small number of quantitative trait loci (QTL) or individual QTL with large effects. In this paper, we investigate the performance of using a weighted genomic relationship matrix (wG) that takes into consideration the genetic architecture of the trait in order to improve predictive ability for a wide range of traits. Multiple methods were used to calculate weights for several economically relevant traits in US Holstein dairy cattle. Predictive performance was tested by k-means cross-validation.ResultsRelaxing the GBLUP assumption of equal marker contribution by increasing the weight that is given to a specific marker in the construction of the trait-specific G resulted in increased predictive performance. The increase was strongest for traits that are controlled by a small number of QTL (e.g. fat and protein percentage). Furthermore, bias in prediction estimates was reduced compared to that resulting from the use of regular G. Even for traits with low heritability and lower general predictive performance (e.g. calving ease traits), weighted G still yielded a gain in accuracy.ConclusionsGenomic relationship matrices weighted by marker realized variance yielded more accurate and less biased predictions for traits regulated by few QTL. Genome-wide association analyses were used to derive marker weights for creating weighted genomic relationship matrices. However, this can be cumbersome and prone to low stability over generations because of erosion of linkage disequilibrium between markers and QTL. Future studies may include other sources of information, such as functional annotation and gene networks, to better exploit the genetic architecture of traits and produce more stable predictions.

Variance component estimates for alternative litter size traits in swine

Litter size at d 5 (LS5) has been shown to be an effective trait to increase total number born (TNB) while simultaneously decreasing preweaning mortality. The objective of this study was to determine the optimal litter size day for selection (i.e., other than d 5). Traits included TNB, number born alive (NBA), litter size at d 2, 5, 10, 30 (LS2, LS5, LS10, LS30, respectively), litter size at weaning (LSW), number weaned (NW), piglet mortality at d 30 (MortD30), and average piglet birth weight (BirthWt). Litter size traits were assigned to biological litters and treated as a trait of the sow. In contrast, NW was the number of piglets weaned by the nurse dam. Bivariate animal models included farm, year-season, and parity as fixed effects. Number born alive was fit as a covariate for BirthWt. Random effects included additive genetics and the permanent environment of the sow. Variance components were plotted for TNB, NBA, and LS2 to LS30 using univariate animal models to determine how variances changed over time. Additive genetic variance was minimized at d 7 in Large White and at d 14 in Landrace pigs. Total phenotypic variance for litter size traits decreased over the first 10 d and then stabilized. Heritability estimates increased between TNB and LS30. Genetic correlations between TNB, NBA, and LS2 to LS29 with LS30 plateaued within the first 10 d. A genetic correlation with LS30 of 0.95 was reached at d 4 for Large White and at d 8 for Landrace pigs. Heritability estimates ranged from 0.07 to 0.13 for litter size traits and MortD30. Birth weight had an h of 0.24 and 0.26 for Large White and Landrace pigs, respectively. Genetic correlations among LS30, LSW, and NW ranged from 0.97 to 1.00. In the Large White breed, genetic correlations between MortD30 with TNB and LS30 were 0.23 and -0.64, respectively. These correlations were 0.10 and -0.61 in the Landrace breed. A high genetic correlation of 0.98 and 0.97 was observed between LS10 and NW for Large White and Landrace breeds, respectively. This would indicate that NW could possibly be used as an effective maternal trait, given a low level of cross-fostering, to avoid back calculating litter size traits from piglet records. Litter size at d 10 would be a compromise between gain in litter size at weaning and minimizing the potentially negative effects of the nurse dam and direct additive genetics of the piglets, as they are expected to increase throughout lactation.

Genome-wide association study on legendre random regression coefficients for the growth and feed intake trajectory on Duroc Boars

BackgroundFeed intake and growth are economically important traits in swine production. Previous genome wide association studies (GWAS) have utilized average daily gain or daily feed intake to identify regions that impact growth and feed intake across time. The use of longitudinal models in GWAS studies, such as random regression, allows for SNPs having a heterogeneous effect across the trajectory to be characterized. The objective of this study is therefore to conduct a single step GWAS (ssGWAS) on the animal polynomial coefficients for feed intake and growth.ResultsCorrected daily feed intake (DFIAdj) and average daily weight measurements (DBWAvg) on 8981 (n = 525,240 observations) and 5643 (n = 283,607 observations) animals were utilized in a random regression model using Legendre polynomials (order = 2) and a relationship matrix that included genotyped and un-genotyped animals. A ssGWAS was conducted on the animal polynomials coefficients (intercept, linear and quadratic) for animals with genotypes (DFIAdj: n = 855; DBWAvg: n = 590). Regions were characterized based on the variance of 10-SNP sliding windows GEBV (WGEBV). A bootstrap analysis (n =1000) was conducted to declare significance. Heritability estimates for the traits trajectory ranged from 0.34-0.52 to 0.07-0.23 for DBWAvg and DFIAdj, respectively. Genetic correlations across age classes were large and positive for both DBWAvg and DFIAdj, albeit age classes at the beginning had a small to moderate genetic correlation with age classes towards the end of the trajectory for both traits. The WGEBV variance explained by significant regions (P < 0.001) for each polynomial coefficient ranged from 0.2-0.9 to 0.3-1.01 % for DBWAvg and DFIAdj, respectively. The WGEBV variance explained by significant regions for the trajectory was 1.54 and 1.95 % for DBWAvg and DFIAdj. Both traits identified candidate genes with functions related to metabolite and energy homeostasis, glucose and insulin signaling and behavior.ConclusionsWe have identified regions of the genome that have an impact on the intercept, linear and quadratic terms for DBWAvg and DFIAdj. These results provide preliminary evidence that individual growth and feed intake trajectories are impacted by different regions of the genome at different times.

Thin and fat cows, and the nonlinear genetic relationship between body condition score and fertility

Thin and fat cows are often credited for low fertility, but body condition score (BCS) has been traditionally treated as a linear trait when genetic correlations with reproductive performance have been estimated. The aims of this study were to assess genetic parameters for fertility, production, and body condition traits in the Brown Swiss population reared in the Alps (Bolzano-Bozen Province, Italy), and to investigate the possible nonlinearity among BCS and other traits by analyzing fat and thin cows. Records of BCS measured on a 5-point scale were preadjusted for year-season and days in milk at scoring, and were considered positive (1) for fat cows if they exceeded the value of 1 residual standard deviation or null (0) otherwise, whereas positive values for thin cows were imputed to records below -1 residual standard deviation. Fertility indicators measured on first- and second-parity cows were interval from parturition to first service, interval from first service to conception, interval from parturition to conception, number of inseminations to conception, conception at first service, and nonreturn rate at 56 d after first service. Production traits were peak milk yield, lactation milk yield, and lactation length. Data were from 1,413 herds and included 16,324 records of BCS, fertility, and production for first-parity, and 10,086 fertility records for second-parity cows. Animals calved from 2002 to 2007 and were progeny of 420 artificial insemination bulls. Genetic parameters for the aforementioned traits were obtained under univariate and bivariate threshold and censored linear sire models implemented in a Bayesian framework. Posterior means of heritabilities for BCS, fat cows, and thin cows were 0.141, 0.122, and 0.115, respectively. Genetic correlations of body condition traits with contemporary production were moderate to high and were between -0.556 and 0.623. Body condition score was moderately related to fertility in first (-0.280 to 0.497) and second (-0.392 to 0.248) lactation. The fat cow trait was scarcely related to fertility, particularly in first-parity cows (-0.203 to 0.281). Finally, the genetic relationships between thin cows and fertility were higher than those between BCS and fertility, both in first (-0.456 to 0.431) and second (-0.335 to 0.524) lactation. Body condition score can be considered a predictor of fertility, and it could be included in evaluation either as linear measure or as thin cow. In the second case, the genetic relationship with fertility was stronger, exacerbating the poorest body condition and considering the possible nonlinearity between fertility and energy reserves of the cow.

Host contributes to longitudinal diversity of fecal microbiota in swine selected for lean growth

BackgroundIn pigs, gut bacteria have been shown to play important roles in nutritional, physiological, and immunological processes in the host. However, the contribution of their metagenomes or part of them, which are normally reflected by fragments of 16S rRNA-encoding genes, has yet to be fully investigated.ResultsFecal samples, collected from a population of crossbred pigs at three time points, including weaning, week 15 post weaning (hereafter “week 15”), and end-of-feeding test (hereafter “off-test”), were used to evaluate changes in the composition of the fecal microbiome of each animal over time. This study used 1205, 1295, and 1283 samples collected at weaning, week 15, and off-test, respectively. There were 1039 animals that had samples collected at all three time points and also had phenotypic records on back fat thickness (BF) and average daily body weight gain (ADG). Firmicutes and Bacteroidetes were the most abundant phyla at all three time points. The most abundant genera at all three time points included Clostridium, Escherichia, Bacteroides, Prevotella, Ruminococcus, Fusobacterium, Campylobacter, Eubacterium, and Lactobacillus. Two enterotypes were identified at each time point. However, only enterotypes at week 15 and off-test were significantly associated with BF. We report herein two novel findings: (i) alpha diversity and operational taxonomic unit (OTU) richness were moderately heritable at week 15, h2 of 0.15 ± 0.06 to 0.16 ± 0.07 and 0.23 ± 0.09 to 0.26 ± 0.08, respectively, as well as at off-test, h2 of 0.20 ± 0.09 to 0.33 ± 0.10 and 0.17 ± 0.08 to 0.24 ± 0.08, respectively, whereas very low heritability estimates for both measures were detected at weaning; and (ii) alpha diversity at week 15 had strong and negative genetic correlations with BF, − 0.53 ± 0.23 to − 0.45 ± 0.25, as well as with ADG, − 0.53 ± 0.32 to − 0.53 ± 0.29.ConclusionsThese results are important for efforts to genetically improve the domesticated pig because they suggest fecal microbiota diversity can be used as an indicator trait to improve traits that are expensive to measure.

Characterization of buffalo production of northeast of Italy

Abstract Aim of this study was to characterize the buffalo production in the Veneto region of Italy. Test day records of milk production traits (milk yield, protein, fat, and somatic cell count) of 845 buffalo cows from two herds were analyzed using a linear model. The effects included in the model were herd-test-day, days in milk, and parity. Days in milk was the most important source of variation for milk yield, protein, and fat. The patterns of milk yield traits across lactation followed the typical trend of buffalo cows. Results allowed a preliminary characterization of buffalo production in north of Italy.

Geno-Diver: A combined coalescence and forward-in-time simulator for populations undergoing selection for complex traits

Geno-Diver is a combined coalescence and forward-in-time simulator designed to simulate complex traits with a quantitative and/or fitness component and implement multiple selection and mating strategies utilizing pedigree or genomic information. The simulation is carried out in two steps. The first step generates whole-genome sequence data for founder individuals. A variety of trait architectures can be generated for quantitative and fitness traits along with their covariance. The second step generates new individuals forward-in-time based on a variety of selection and mating scenarios. Genetic values are predicted for individuals utilizing pedigree or genomic information. Relationship matrices and their associated inverses are generated using computationally efficient routines. We benchmarked Geno-Diver with a previous simulation program and described how to simulate a traditional quantitative trait along with a quantitative and fitness trait. A user manual with examples, source code in C++11 and executable versions of Geno-Diver for Linux are freely available at https://github.com/jeremyhoward/Geno-Diver.

Short communication: Genomic selection for hoof lesions in first-parity US Holsteins

Hoof lesions contributing to lameness are crucial economic factors that hinder the profitability of dairy enterprises. Producer-recorded hoof lesions data of US Holsteins were categorized into infectious (abscess, digital and interdigital dermatitis, heel erosion, and foot rot) and noninfectious (korn, corkscrew, sole and toe ulcer, sole hemorrhage, white line separation, fissures, thin soles, and upper leg lesions) categories of hoof lesions. Pedigree- and genomic-based univariate analyses were conducted to estimate the variance components and heritability of infectious and noninfectious hoof lesions. A threshold sire model was used with fixed effects of year-seasons and random effects of herd and sire. For genomic-based analysis, a single-step procedure was conducted, incorporating H matrix to estimate genomic variance components and heritability for hoof lesions. The pedigree-based analysis produced heritability estimates of 0.11 (±0.05) for infectious hoof lesions and 0.08 (±0.05) for noninfectious hoof lesions. The single-step genomic analysis produced heritability estimates of 0.14 (±0.06) for infectious hoof lesions and 0.12 (±0.08) for noninfectious hoof lesions. Approximated genetic correlations between hoof lesion traits and hoof type traits along with productive life and net merit were all low and ranged between -0.25 and 0.14. Sire reliabilities increased, on average, by 0.24 and 0.18 for infectious and noninfectious hoof lesions, respectively, with incorporation of genomic data.

Genomic prediction of disease occurrence using producer-recorded health data: a comparison of methods

BackgroundGenetic selection has been successful in achieving increased production in dairy cattle; however, corresponding declines in fitness traits have been documented. Selection for fitness traits is more difficult, since they have low heritabilities and are influenced by various non-genetic factors. The objective of this paper was to investigate the predictive ability of two-stage and single-step genomic selection methods applied to health data collected from on-farm computer systems in the U.S.MethodsImplementation of single-trait and two-trait sire models was investigated using BayesA and single-step methods for mastitis and somatic cell score. Variance components were estimated. The complete dataset was divided into training and validation sets to perform model comparison. Estimated sire breeding values were used to estimate the number of daughters expected to develop mastitis. Predictive ability of each model was assessed by the sum of χ2 values that compared predicted and observed numbers of daughters with mastitis and the proportion of wrong predictions.ResultsAccording to the model applied, estimated heritabilities of liability to mastitis ranged from 0.05 (SD=0.02) to 0.11 (SD=0.03) and estimated heritabilities of somatic cell score ranged from 0.08 (SD=0.01) to 0.18 (SD=0.03). Posterior mean of genetic correlation between mastitis and somatic cell score was equal to 0.63 (SD=0.17). The single-step method had the best predictive ability. Conversely, the smallest number of wrong predictions was obtained with the univariate BayesA model. The best model fit was found for single-step and pedigree-based models. Bivariate single-step analysis had a better predictive ability than bivariate BayesA; however, the latter led to the smallest number of wrong predictions.ConclusionsGenomic data improved our ability to predict animal breeding values. Performance of genomic selection methods depends on a multitude of factors. Heritability of traits and reliability of genotyped individuals has a large impact on the performance of genomic evaluation methods. Given the current characteristics of producer-recorded health data, single-step methods have several advantages compared to two-step methods.