Understanding genomic prediction in chickens

Genomic prediction (GP) is a novel tool used for prediction of EBVs by using molecular markers. Within the last decade, GP has been widely introduced into routine evaluations of cattle, pig and sheep populations, however, its application in poultry has been somewhat delayed, and studies published to date have been limited in terms of population size and marker densities. This study shows a thorough evaluation of the benefits that GP could bring into routine evaluations of broiler chickens, with particular attention given to the accuracy and bias of Genomic BLUP (GBLUP) predictions. The data used for these evaluations exceeds the numbers of both individuals and marker genotypes of previously published reports, with the studied population consisting of up to 23,500 individuals, genotyped for up to 600K SNPs. The evaluation of GBLUP is preceded by evaluation of the variance components using traditional restricted maximum likelihood (REML) approach sourcing information from phenotypic records and pedigree, which provide an up to date reference for the estimates of variance components. Chapter 2 tested several models exploring potential sources of genetic variation and revealed the presence of significant maternal genetic and environmental effects affecting several commercial traits. In Chapter 3, a vast dataset containing 1.3M birds spread over 24 generations was used to evaluate changes in genetic variance of juvenile body weight and hen housed production over time. The results showed a slow but steady decline of the variance. Chapter 4 provided initial estimates of the accuracy and bias of genomic predictions for several sex-limited and fitness traits, obtained for a moderately sized population of over 5K birds, genotyped with 600K Affymetrix Axiom panel from which several chips of varying marker densities were extracted. The accuracy of those predictions showed a great potential for most traits, with GBLUP performance exceeding that of traditional BLUP. Chapter 5 investigated the effect of marker choice, with two chips used: one created from GWAS hits and second from evenly spaced markers, both with constant density of 27K SNPs. The two chips were used to calculate genomic relationship matrices using Linkage Analysis and Linkage Disequilibrium approaches. Markers selected through GWAS performed better in Linkage Analysis than in Linkage Disequilibrium approach. The optimum results however were found for relationship matrices which regressed the genomic relationships back to expected pedigree-based relationships, with the best regression coefficient dependent on the chip used. Chapter 6 formed a comprehensive evaluation of the utility of GBLUP in a large broiler population, exceeding 23,500 birds genotyped using 600K Affymetrix Axiom panel. By splitting the data into variable scenarios of training and testing populations, with several lower density chips extracted from the full range of genotypes available, the effect of population size and marker density was evaluated. While the latter proved to have little effect once 20K SNPs threshold was exceeded, the effect of the population size was found to be the major limiting factor for the accuracy of EBV predictions. The discrepancy between empirical results found and theoretical expectations of accuracy based on the similar genomic and population parameters showed an underestimation of the previously proposed requirements

Additive and non-additive genetic variance in juvenile Sitka spruce (Picea sitchensis Bong. Carr)

Many quantitative genetic models assume that all genetic variation is additive because of a lack of data with sufficient structure and quality to determine the relative contribution of additive and non-additive variation. Here the fractions of additive (fa) and non-additive (fd) genetic variation were estimated in Sitka spruce for height, bud burst and pilodyn penetration depth. Approximately 1500 offspring were produced in each of three sib families and clonally replicated across three geographically diverse sites. Genotypes from 1525 offspring from all three families were obtained by RADseq, followed by imputation using 1630 loci segregating in all families and mapped using the newly developed linkage map of Sitka spruce. The analyses employed a new approach for estimating fa and fd, which combined all available genotypic and phenotypic data with spatial modelling for each trait and site. The consensus estimate for fa increased with age for height from 0.58 at 2 years to 0.75 at 11 years, with only small overlap in 95% support intervals (I95). The estimated fa for bud burst was 0.83 (I95=[0.78, 0.90]) and 0.84 (I95=[0.77, 0.92]) for pilodyn depth. Overall, there was no evidence of family heterogeneity for height or bud burst, or site heterogeneity for pilodyn depth, and no evidence of inbreeding depression associated with genomic homozygosity, expected if dominance variance was the major component of non-additive variance. The results offer no support for the development of sublines for crossing within the species. The models give new opportunities to assess more accurately the scale of non-additive variation

A genome-wide association analysis for body weight at 35 days measured on 137,343 broiler chickens

Background: Body weight (BW) is an economically important trait in the broiler (meat-type chickens) industry. Under the assumption of polygenicity, a "large" number of genes with "small" effects is expected to control BW. To detect such effects, a large sample size is required in genome-wide association studies (GWAS). Our objective was to conduct a GWAS for BW measured at 35 days of age with a large sample size.Methods: The GWAS included 137,343 broilers spanning 15 pedigree generations and 392,295 imputed single nucleotide polymorphisms (SNPs). A false discovery rate of 1% was adopted to account for multiple testing when declaring significant SNPs. A Bayesian ridge regression model was implemented, using AlphaBayes, to estimate the contribution to the total genetic variance of each region harbouring significant SNPs (1 Mb up/downstream) and the combined regions harbouring non-significant SNPs.Results: GWAS revealed 25 genomic regions harbouring 96 significant SNPs on 13 Gallus gallus autosomes (GGA1 to 4, 8, 10 to 15, 19 and 27), with the strongest associations on GGA4 at 65.67-66.31 Mb (Galgal4 assembly). The association of these regions points to several strong candidate genes including: (i) growth factors (GGA1, 4, 8, 13 and 14); (ii) leptin receptor overlapping transcript (LEPROT)/leptin receptor (LEPR) locus (GGA8), and the STAT3/STAT5B locus (GGA27), in connection with the JAK/STAT signalling pathway; (iii) T-box gene (TBX3/TBX5) on GGA15 and CHST11 (GGA1), which are both related to heart/skeleton development); and (iv) PLAG1 (GGA2). Combined together, these 25 genomic regions explained similar to 30% of the total genetic variance. The region harbouring significant SNPs that explained the largest portion of the total genetic variance (4.37%) was on GGA4 (similar to 65.67-66.31 Mb).Conclusions: To the best of our knowledge, this is the largest GWAS that has been conducted for BW in chicken to date. In spite of the identified regions, which showed a strong association with BW, the high proportion of genetic variance attributed to regions harbouring non-significant SNPs supports the hypothesis that the genetic architecture of BW35 is polygenic and complex. Our results also suggest that a large sample size will be required for future GWAS of BW35

Use and optimization of different sources of information for genomic prediction

Abstract Background Molecular data is now commonly used to predict breeding values (BV). Various methods to calculate genomic relationship matrices (GRM) have been developed, with some studies proposing regression of coefficients back to the reference matrix of pedigree-based relationship coefficients (A). The objective was to compare the utility of two GRM: a matrix based on linkage analysis (LA) and anchored to the pedigree, i.e. $${\mathbf{G}}_{{{\mathbf{LA}}}} ,$$ G LA , and a matrix based on linkage disequilibrium (LD), i.e. $${\mathbf{G}}_{{{\mathbf{LD}}}}$$ G LD , using genomic and phenotypic data collected on 5416 broiler chickens. Furthermore, the effects of regressing the coefficients of $${\mathbf{G}}_{{{\mathbf{LD}}}}$$ G LD back to A (LDA) and to $${\mathbf{G}}_{{{\mathbf{LA}}}}$$ G LA (LDLA) were evaluated, using a range of weighting factors. The performance of the matrices and their composite products was assessed by the fit of the models to the data, and the empirical accuracy and bias of the BV that they predicted. The sensitivity to marker choice was examined by using two chips of equal density but including different single nucleotide polymorphisms (SNPs). Results The likelihood of models using GRM and composite matrices exceeded the likelihood of models based on pedigree alone and was highest with intermediate weighting factors for both the LDA and LDLA approaches. For these data, empirical accuracies were not strongly affected by the weighting factors, although they were highest when different sources of information were combined. The optimum weighting factors depended on the type of matrices used, as well as on the choice of SNPs from which the GRM were constructed. Prediction bias was strongly affected by the chip used and less by the form of the GRM. Conclusions Our findings provide an empirical comparison of the efficacy of pedigree and genomic predictions in broiler chickens and examine the effects of fitting GRM with coefficients regressed back to a reference anchored to the pedigree, either A or $${\mathbf{G}}_{{{\mathbf{LA}}}}$$ G LA . For the analysed dataset, the best results were obtained when $${\mathbf{G}}_{{{\mathbf{LD}}}}$$ G LD was combined with relationships in A or $${\mathbf{G}}_{{{\mathbf{LA}}}}$$ G LA , with optimum weighting factors that depended on the choice of SNPs used. The optimum weighting factor for broiler body weight differed from weighting factors that were based on the density of SNPs and theoretically derived using generalised assumptions

Method specific calibration corrects for DNA extraction method effects on relative telomere length measurements by quantitative PCR

Telomere length (TL) is increasingly being used as a biomarker in epidemiological, biomedical and ecological studies. A wide range of DNA extraction techniques have been used in telomere experiments and recent quantitative PCR (qPCR) based studies suggest that the choice of DNA extraction method may influence average relative TL (RTL) measurements. Such extraction method effects may limit the use of historically collected DNA samples extracted with different methods. However, if extraction method effects are systematic an extraction method specific (MS) calibrator might be able to correct for them, because systematic effects would influence the calibrator sample in the same way as all other samples. In the present study we tested whether leukocyte RTL in blood samples from Holstein Friesian cattle and Soay sheep measured by qPCR was influenced by DNA extraction method and whether MS calibration could account for any observed differences. We compared two silica membrane-based DNA extraction kits and a salting out method. All extraction methods were optimized to yield enough high quality DNA for TL measurement. In both species we found that silica membrane-based DNA extraction methods produced shorter RTL measurements than the non-membrane-based method when calibrated against an identical calibrator. However, these differences were not statistically detectable when a MS calibrator was used to calculate RTL. This approach produced RTL measurements that were highly correlated across extraction methods (r > 0.76) and had coefficients of variation lower than 10% across plates of identical samples extracted by different methods. Our results are consistent with previous findings that popular membrane-based DNA extraction methods may lead to shorter RTL measurements than non-membrane-based methods. However, we also demonstrate that these differences can be accounted for by using an extraction method-specific calibrator, offering researchers a simple means of accounting for differences in RTL measurements from samples extracted by different DNA extraction methods within a study

Longitudinal changes in telomere length and associated genetic parameters in dairy cattle analysed using random regression models

Telomeres cap the ends of linear chromosomes and shorten with age in many organisms. In humans short telomeres have been linked to morbidity and mortality. With the accumulation of longitudinal datasets the focus shifts from investigating telomere length (TL) to exploring TL change within individuals over time. Some studies indicate that the speed of telomere attrition is predictive of future disease. The objectives of the present study were to 1) characterize the change in bovine relative leukocyte TL (RLTL) across the lifetime in Holstein Friesian dairy cattle, 2) estimate genetic parameters of RLTL over time and 3) investigate the association of differences in individual RLTL profiles with productive lifespan. RLTL measurements were analysed using Legendre polynomials in a random regression model to describe TL profiles and genetic variance over age. The analyses were based on 1,328 repeated RLTL measurements of 308 female Holstein Friesian dairy cattle. A quadratic Legendre polynomial was fitted to the fixed effect of age in months and to the random effect of the animal identity. Changes in RLTL, heritability and within-trait genetic correlation along the age trajectory were calculated and illustrated. At a population level, the relationship between RLTL and age was described by a positive quadratic function. Individuals varied significantly regarding the direction and amount of RLTL change over life. The heritability of RLTL ranged from 0.36 to 0.47 (SE = 0.05–0.08) and remained statistically unchanged over time. The genetic correlation of RLTL at birth with measurements later in life decreased with the time interval between samplings from near unity to 0.69, indicating that TL later in life might be regulated by different genes than TL early in life. Even though animals differed in their RLTL profiles significantly, those differences were not correlated with productive lifespan (p = 0.954)