Dj De Koning

Segregation of QTL for production traits in commercial meat-type chickens.

This study investigated whether quantitative trait loci (QTL) identified in experimental crosses of chickens provide a short cut to the identification of QTL in commercial populations. A commercial population of broilers was targeted for chromosomal regions in which QTL for traits associated with meat production have previously been detected in extreme crosses. A three-generation design, consisting of 15 grandsires, 608 half-sib hens and over 15 000 third-generation offspring, was implemented within the existing breeding scheme of a broiler breeding company. The first two generations were typed for 52 microsatellite markers spanning regions of nine chicken chromosomes and covering a total of 730 cM, approximately one-fifth of the chicken genome. Using half-sib analyses with a multiple QTL model, linkage was studied between these regions and 17 growth and carcass traits. Out of 153 trait x region comparisons, 53 QTL exceeded the threshold for genome-wide significance while an additional 23 QTL were significant at the nominal 1% level. Many of the QTL affect the carcass proportions and feed intake, for which there are few published studies. Given intensive selection for efficient growth in broilers for more than 50 generations it is surprising that many QTL affecting these traits are still segregating. Future fine-mapping efforts could elucidate whether ancestral mutations are still segregating as a result of pleiotropic effects on fitness traits or whether this variation is due to new mutations.

Quantitative trait loci for resistance to fish pasteurellosis in gilthead sea bream (Sparus aurata)

Fish pasteurellosis is a bacterial disease causing important losses in farmed fish, including gilthead sea bream, a teleost fish of great relevance in marine aquaculture. We report in this study a QTL analysis for resistance to fish pasteurellosis in this species. An experimental population of 500 offspring originating from eight sires and six dams in a single mass-spawning event was subjected to a disease challenge with Photobacterium damselae subsp. piscicida (Phdp), the causative agent of fish pasteurellosis. A total of 151 microsatellite loci were genotyped in the experimental population, and half-sib regression QTL analysis was carried out on two continuous traits, body length at time of death and survival, and for two binary traits, survival at day 7 and survival at day 15, when the highest peaks of mortality were observed. Two significant QTLs were detected for disease resistance. The first one was located on linkage group LG3 affecting late survival (survival at day 15). The second one, for overall survival, was located on LG21, which allowed us to highlight a potential marker (Id13) linked to disease resistance. A significant QTL was also found for body length at death on LG6 explaining 5-8% of the phenotypic variation.

High throughput analyses of epistasis for swine body dimensions and organ weights

High throughput analyses were performed to detect epistatic QTL in 17 body dimension and organ weight traits from a large F(2) pig population derived from a White Duroc and Erhualian intercross. The analyses used a nested test framework to handle multiple tests and a combined search algorithm to map epistatic QTL with empirical genome-wide thresholds derived via prior permutation. Alternative statistical models (e.g. including vs. excluding carcass weight as a covariate) were tested to develop an in-depth understanding of the role of epistasis in these kinds of traits. Epistasis signals were detected in only two or three traits under each statistical model studied. The interaction component of each pair of epistatic QTL explained a small proportion (0.7 to 2.1%) of the phenotypic variance in general. About half of the detected epistatic QTL pairs involved one of the two major QTL on porcine chromosomes 7 and 4. In those traits, the Erhualian allele consistently increased the phenotypes for the chromosome 7 QTL but decreased them for the chromosome 4 QTL. Models including carcass weight as covariate detected epistasis in body dimension traits whereas those excluding carcass weight found epistasis in organ weight traits. In addition, the epistasis results suggested that a QTL on chromosome 14 could be important for a number of organ weight traits. Using the high-throughput analysis tool to examine different statistical models was essential for the generation of a complete picture of epistasis in a whole category of traits.

Efficiency of genomic prediction for boar taint reduction in Danish Landrace pigs

Summary Genetic selection against boar taint, which is caused by high skatole and androstenone concentrations in fat, is a more acceptable alternative than is the current practice of castration. Genomic predictors offer an opportunity to overcome the limitations of such selection caused by the phenotype being expressed only in males at slaughter, and this study evaluated different approaches to obtain such predictors. Samples from 1000 pigs were included in a design which was dominated by 421 sib pairs, each pair having one animal with high and one with low skatole concentration (≥0.3 μg/g). All samples were measured for both skatole and androstenone and genotyped using the Illumina SNP60 porcine BeadChip for 62 153 single nucleotide polymorphisms. The accuracy of predicting phenotypes was assessed by cross‐validation using six different genomic evaluation methods: genomic best linear unbiased prediction (GBLUP) and five Bayesian regression methods. In addition, this was compared to the accuracy of predictions using only QTL that showed genome‐wide significance. The range of accuracies obtained by different prediction methods was narrow for androstenone, between 0.29 (Bayes Lasso) and 0.31 (Bayes B), and wider for skatole, between 0.21 (GBLUP) and 0.26 (Bayes SSVS). Relative accuracies, corrected for h 2, were 0.54–0.56 and 0.75–0.94 for androstenone and skatole respectively. The whole‐genome evaluation methods gave greater accuracy than using only the QTL detected in the data. The results demonstrate that GBLUP for androstenone is the simplest genomic technology to implement and was also close to the most accurate method. More specialised models may be preferable for skatole.

Complex traits analysis of chicken growth using targeted genetical genomics

Dissecting the genetic control of complex trait variation remains very challenging, despite many advances in technology. The aim of this study was to use a major growth quantitative trait locus (QTL) in chickens mapped to chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a variant of the genetical genomics approach to investigate genome-wide gene expression differences between two contrasting genotypes of a marked QTL. This targeted approach allows the direct quantification of the link between the genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics studies. Four differentially expressed genes were localized under the region of the QTL. One of these genes is a potential positional candidate gene (AADAT) that affects lysine and tryptophan metabolism and has alternative splicing variants between the two genotypes. In addition, the lysine and glycolysis metabolism pathways were significantly enriched for differentially expressed genes across the genome. The targeted approach provided a complementary route to fine mapping of QTL by characterizing the local and the global downstream effects of the QTL and thus generating further hypotheses about the action of that QTL.

Genomewide rapid association using mixed model and regression

For pedigree-based quantitative trait loci (QTL) association analysis, a range of methods utilizing within-family variation such as transmission-disequilibrium test (TDT)-based methods have been developed. In scenarios where stratification is not a concern, methods exploiting between-family variation in addition to within-family variation, such as the measured genotype (MG) approach, have greater power. Application of MG methods can be computationally demanding (especially for large pedigrees), making genomewide scans practically infeasible. Here we suggest a novel approach for genomewide pedigree-based quantitative trait loci (QTL) association analysis: genomewide rapid association using mixed model and regression (GRAMMAR). The method first obtains residuals adjusted for family effects and subsequently analyzes the association between these residuals and genetic polymorphisms using rapid least-squares methods. At the final step, the selected polymorphisms may be followed up with the full measured genotype (MG) analysis. In a simulation study, we compared type 1 error, power, and operational characteristics of the proposed method with those of MG and TDT-based approaches. For moderately heritable (30%) traits in human pedigrees the power of the GRAMMAR and the MG approaches is similar and is much higher than that of TDT-based approaches. When using tabulated thresholds, the proposed method is less powerful than MG for very high heritabilities and pedigrees including large sibships like those observed in livestock pedigrees. However, there is little or no difference in empirical power of MG and the proposed method. In any scenario, GRAMMAR is much faster than MG and enables rapid analysis of hundreds of thousands of markers.

Integrating QTL mapping, gene-expression and next-generation sequencing to unravel a QTL affecting meat quality in chicken

Poor lamb survival is a major cause of reproductive inefficiency in sheep flocks in many countries. Since 2007, the Australian Cooperative Research Centre for Sheep Industry Innovation (the Sheep CRC) has had a major project on reproduction efficiency to help industry wean an extra 1 million lambs per year by 2014 from the national flock, the key target being improved neonatal lamb survival. In addition, work is also directed at improving post-weaning survival. This paper provides an overview of the project, its key findings and achievements to date, focussing on neonatal lamb survival.

Genome-wide Association using a 60k SNP chip to explore the genomic control of boar taint in pigs

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