Search

BACKGROUND: Bone damage has welfare and economic impacts on modern commercial poultry and is known as one of the major challenges in the poultry industry. Bone damage is particularly common in laying hens and is probably due to the physiological link between bone and the egg laying process. Previous studies identified and validated quantitative trait loci (QTL) for bone strength in White Leghorn laying hens based on several measurements, including bone composition measurements on the cortex and medulla of the tibia bone. In a previous pedigree-based analysis, bone composition measurements showed heritabilities ranging from 0.18 to 0.41 and moderate to strong genetic correlations with tibia strength and density. Bone composition was measured using infrared spectroscopy and thermogravimetry. The aim of this study was to combine these bone composition measurements with genotyping data via a genome-wide association study (GWAS) to investigate genetic markers that contribute to genetic variance in bone composition in Rhode Island Red laying hens. In addition, we investigated the genetic correlations between bone composition and bone strength.RESULTS: We found novel genetic markers that are significantly associated with cortical lipid, cortical mineral scattering, medullary organic matter, and medullary mineralization. Composition of the bone organic matter showed more significant associations than bone mineral composition. We also found interesting overlaps between the GWAS results for tibia composition traits, particularly for cortical lipid and tibia strength. Bone composition measurements by infrared spectroscopy showed more significant associations than thermogravimetry measurements. Based on the results of infrared spectroscopy, cortical lipid showed the highest genetic correlations with tibia density, which was negative (- 0.20 ± 0.04), followed by cortical CO3/PO4 (0.18 ± 0.04). Based on the results of thermogravimetry, medullary organic matter% and mineral% showed the highest genetic correlations with tibia density (- 0.25 ± 0.04 and 0.25 ± 0.04, respectively).CONCLUSIONS: This study detected novel genetic associations for bone composition traits, particularly those involving organic matter, that could be used as a basis for further molecular genetic investigations. Tibia cortical lipids displayed the strongest genetic associations of all the composition measurements, including a significantly high genetic correlation with tibia density and strength. Our results also highlighted that cortical lipid may be a key measurement for further avian bone studies.

Routine implementation of genomic information for guiding selection decisions is not yet common in the majority of aquaculture species. Reduced representation sequencing approaches offer a cost-effective solution for obtaining genome-wide information in species with a limited availability of genomic resources. In the current study, we implemented double-digest restriction site-associated DNA sequencing (ddRAD-seq) on an Arctic charr strain with the longest known history of selection (approximately 40 years) aiming to improve selection decisions. In total, 1730 animals reared at four different farms in Sweden and spanning from year classes 2013-2017 were genotyped using ddRAD-seq. Approximately 5000 single nucleotide polymorphisms (SNPs) were identified, genetic diversity-related metrics were estimated, and genome-wide association studies (GWAS) for body length at different time points and age of sexual maturation were conducted. Low genetic differentiation amongst animals from the different farms was observed based on both the results from pairwise F-st values and principal component analysis (PCA). The existence of associations was investigated between the mean genome-wide heterozygosity of each full-sib family (year class 2017) and the corresponding inbreeding coefficient or survival to the eyed stage. A moderate correlation (-0.33) was estimated between the mean observed heterozygosity of each full-sib family and the corresponding inbreeding coefficient, while no linear association was obtained with the survival to the eyed stage. GWAS did not detect loci with major effect for any of the studied traits. However, genomic regions explaining more than 1% of the additive genetic variance for either studied traits were suggested across 14 different chromosomes. Overall, key insights valuable for future selection decisions of Arctic charr have been obtained, suggesting ddRAD as an attractive genotyping platform for obtaining genome-wide information in a cost-effective manner.

Supplemental tables for the manuscript Sallam et al. (2022):Across-countries genomic prediction using national breeding values or multitrait across-countries evaluation breeding valuesM. Sallam, H. Benhajali, S. Savoia, D. J. de Koning, and E. Strandberg** Manuscript in Journal of Dairy Science

Skeletal damage is a challenge for laying hens, as the adaptations for egg laying make them susceptible to osteoporosis. We know that activity, growth and puberty influence skeletal quality genetics. However, in this story, we follow the process of resolving a QTL for skeletal quality to a single gene. Providing both a nutritional and a genetic solution and illustrating another level of complexity. Using divergently selected populations in an F2 cross, a QTL for skeletal quality was described. Utilising a series of experiments in the commercial founder line the QTL was fine mapped on chromosome 1 and the differences in physiology of hens that segregated for markers at the locus defined e.g. tibia breaking strength 200.4 vs 218.1 Newton (p< 0.002). Transcriptome profiling of tibia from the high and low bone strength genotype revealed a highly differentially expressed gene co localising to the QTL, the enzyme cystathionine beta synthase (CBS). CBS is a component of one carbon metabolism. Plasma homocysteine, the substrate of CBS had a higher concentration in the genotype associated with poor bone quality. Homocysteine interferes with crosslinking of the collagen matrix, critical to bone formation. Homocysteine can be re-methylated into methionine, a limiting amino acid in laying hens, using betaine as a methyl donor. Testing the hypothesis that reducing plasma homocysteine by feeding betaine, a widely available feed additive, would improve bone quality in laying hens proved successful.This is just one component of a complex trait and its elucidation took us along unexpected routes. However, I am optimistic that with modern tools and an open mind we can progress more quickly. Alongside understanding the factors that determine skeletal quality genetics, the discovery of the mechanisms behind complex traits, although rarely easy, offer the potential for novel interventions to improve animal health and production.

Additional file 1: Figure S1. Predicted porcine PRDM9 binding site from the amino acid sequence, with reverse complement and the canonical PRDM9 motif for comparison. The sequence logos were generated with the online predictor of [45].

Den här rapporten är framtagen av SLUs vetenskapliga råd för djurskydd i syfte att utvärdera djurvälfärden hos minkar inom svensk pälsdjursproduktion och bedöma om den vetenskapliga litteraturen ger stöd för att produktionen, så som den bedrivs i dag, ger djuren möjlighet att bete sig naturligt. Minkar som föds upp för pälsproduktion i Sverige måste hållas och skötas enligt Statens jordbruksverks föreskrifter och allmänna råd (SJVFS 2012:14) om uppfödning och hållande av pälsdjur. Rapporten har tagits fram på uppdrag av Jordbruksverket som en del i ett regeringsuppdrag om minkhållning. Den beskriver minkens ursprung och domesticering, naturligt beteende hos vild mink, inhysning och skötsel vid pälsuppfödning, onormalt beteende, miljöberikningar, smittskydd, förekommande sjukdomar och avlivningsmetoder. I rapporten ges rekommendationer baserat på tillgänglig vetenskaplig litteratur, och behov av framtida forskning identifieras. Minken är en opportunistisk köttätare som behöver äta relativt ofta. I pälsdjursproduktionen tillämpas i princip fri tillgång på foder till digivande honor och växande valpar men inför parningssäsongen innebär den fria tillgången ökad risk för komplikationer vid valpningen på grund av övervikt hos honan. Fodringen behöver därför anpassas under vintern för att minska risken för feta honor och därmed ökad dödlighet vid valpningen. Neddragen fodertillgång kan orsaka frustration som då visar sig i beteendestörningar. Olika aspekter på utfodring bör därför beaktas i framtida forskning. Den vilda minken lever solitärt under stora delar av året, dock kan en till flera honor leva inom en hanes revir. I pälsdjursproduktionen bör därför vuxna minkar hållas individuellt, undantaget är växande ungminkar som med fördel kan hållas tillsammans. Att hålla två minkar tillsammans är det vanligaste, dock fungerar det att hålla tre ungminkar i etagebur om de ges extra foder och god tillsyn. Grupper med fler än tre djur bör undvikas då riskerna för aggression ökar. En lya fastsatt utanpå buren är viktigt för alla minkar året runt då de naturligt vilar mycket i sina bohål, samt även för att minkhonan ska kunna ta hand om de outvecklade ungarna första tiden efter födelsen. I fångenskap används halm för att skapa ett varmt bo under den kalla årstiden samt för att bygga ett bo för ungarna under uppfödningsperioden. Systematisk genetisk selektion för önskat beteende (temperament) förbättrar välfärden hos minken. Systemet tillämpas på svenska gårdar genom att minkar som uppvisar rädsla eller stress selekteras bort vid avelsurvalet. Urvalet av avelsdjur görs kontinuerligt från det att valparna föds, då reproduktion, valpöverlevnad och temperament registreras tidigt och är viktiga parametrar att ta hänsyn till i urvalet. Det slutliga urvalen sker på hösten då längd, vikt och pälsegenskaper graderas. Ju tidigare dessa urval görs desto tidigare kan utfodringen anpassas för att undvika att avelsdjuren blir överviktiga under hösten. Det är viktigt att aveln inte resulterar i för stora djur, då detta kan leda till välfärdsproblem i framtiden. Mink i vilt tillstånd använder vatten i sin jakt på bytesdjur, men är inget vattenlevande djur, per se. Badvatten till mink bedöms däremot vara en positiv berikning, dock inte vetenskapligt belagt, som ett grundläggande beteendebehov. Forskning visar att beteendestörningar kan förebyggas genom att minkarna ges fri tillgång på foder, hålls i etageburar med bolåda, hyllor, strömedel och berikningar som byts ut regelbundet. I svenska djurskyddsföreskrifter ingår dessa som krav för hållande av mink för pälsdjursproduktion. Mer kunskap behövs för hur ofta berikningar bör skiftas. Djurvälfärd i samband med livdjurstransport och avlivning av mink lyfts fram som angelägna forskningsområden. En snabb avlivning vid hemmaburen bedöms vara det bästa ur djurvälfärdssynpunkt. För att minska risken för spridning av sjukdomar bör importerade minkar hållas i karantän och hög biosäkerhet tillämpas på gården.

I Sverige tillåts idag generellt avvänjning av smågrisar i praktiken vid en individuell ålder om tidigast 28 dagar. Detta skiljer från EUs grisdirektiv där avvänjning tillåts från 21 dagars ålder. En digivningsperiod på 21 dagar ger en högre produktion eftersom medeltalet kullar per sugga och år teoretiskt då kan öka med 4,5 % (från 2,2 till 2,3 kullar per år). Det har även föreslagits att en kortare digivningsperiod skulle innebära mindre påfrestningar på suggorna, och därigenom medföra förbättrad välfärd för dessa. Rådet finner att det finns mycket få studier som jämför avvänjning vid just 21 och 28 dagar. De vetenskapliga studier som studerar detta mer i detalj är i de flesta fall genomförda i alternativa system, så som grupphållnings-system eller så kallade ”getaway pens” där suggan kan gå ifrån sina smågrisar. Resultat från dessa studier går därmed inte att generalisera till konventionella system där suggor med smågrisar hålls individuellt med små möjligheter för suggan att reglera t.ex. digivning eller födosöksbeteende. Trots bristen på vetenskapligt granskade rapporter konstaterades att en avvänjning vid 28 dagars ålder var att föredra sett ur smågrisens perspektiv, eftersom matsmältningsapparat och immunsystem är mer utvecklade den fjärde levnadsveckan. Det förefaller dock finnas en ganska tydlig skillnad i fysiologisk mognad mellan grisar som är yngre (

Breeding programs are crucial for boosting productivity and increase sustainability of aquaculture. Over years, Tanzania has witnessed fluctuation in its capture fisheries production from 320,900 to 375, 535 and back to 362,595 metric tonnes in the years 2000, 2005 and 2016, respectively (URT 2016). The declining trend in fish production has made fish supply in the country unstable and conversely, increased the demand for fishes to about 730,000 metric tonnes in 2017. However, the local aquaculture production has not increased accordingly. Tanzania is importing fish mainly from Asia to meet its increased demand. In 2017, a total of 2,055,721 kg of frozen tilapia were imported from China and Mozambique (URT 2017). The introduction of exotic fish species in Tanzania should be carefully managed because introduced species have many negative impacts to the indigenous species. Tanzania should have a moderate scale tilapia breeding program that will produce good quality fingerlings at affordable price for smallholder fish farmers. The availability of reliable good quality fingerlings is key to improve aquaculture production in the country. Among 17 existing hatcheries, only 12 hatcheries are active, however these hatcheries are not performing well due to low investment and technology leading to the production of low quantity and quality fingerlings. The need for a structured sustainable Tilapia breeding program with bio secured and reliable hatcheries to enhance aquaculture production in Tanzania is given in this review.Keywords: Aquaculture, Breeding programs, Nile tilapia, Local strains.

Biotechnology can provide innovative and efficient tools to support sustainable development of aquaculture. It is generally accepted that use of the term 'genetically modified' causes controversy and conflict among consumers, but little is known about how using the term 'biotechnology' as a salient feature on product packaging affects consumer preferences. In an online discrete choice experiment consisting of two treatments, a set of 1005 randomly chosen Swedish consumers were surveyed about use of hormone and triploidization sterilization techniques for salmonids. The information given to the treatment group included an additional sentence stating that the triploidization technique is an application of biotechnology, while the control group received the same text but without reference to biotechnology. Analysis using a hierarchical Bayes approach revealed significant consumer reactions to the term biotechnology. When the term was included in information, variation in consumer willingness-to-pay (WTP) estimates increased significantly. Moreover, some participants were dissuaded towards an option guaranteeing no biotechnological intervention in production of fish. These results have multiple implications for research and for the food industry. For research, they indicate the importance of examining the distribution of variation in WTP estimates for more complete characterization of the effects of information on consumer behavior. For the food industry, they show that associating food with biotechnology creates more variability in demand. Initiatives should be introduced to reduce the confusion associated with the term biotechnology among consumers.

BackgroundIn this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing load. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. Once deleterious variants have been identified, how can they be used in breeding?ResultsWe simulated a closed animal breeding population subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. Each strategy varied in how animals and variants were prioritized for editing or selection.ConclusionsGenome editing of deleterious alleles reduces deleterious load, but requires simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. The dominance of deleterious variants affects both the efficiency of genome editing and selection against carriers, and which variant prioritization strategy is the most efficient. Our results suggest that in the future, there is the potential to use RAGE against deleterious load in animal breeding.

Because mastitis is very frequent and unavoidable, adding recovery information into the analysis for genetic evaluation of mastitis is of great interest from economical and animal welfare point of view. Here we have performed genome-wide association studies (GWAS) to identify associated single nucleotide polymorphisms (SNPs) and investigate the genetic background not only for susceptibility to – but also for recoverability from mastitis. Somatic cell count records from 993 Danish Holstein cows genotyped for a total of 39378 autosomal SNP markers were used for the association analysis. Single SNP regression analysis was performed using the statistical software package DMU. Substitution effect of each SNP was tested with a t-test and a genome-wide significance level of P-value < 10-4 was used to declare significant SNP-trait association. A number of significant SNP variants were identified for both traits. Many of the SNP variants associated either with susceptibility to – or recoverability from mastitis were located in or very near to genes that have been reported for their role in the immune system. Genes involved in lymphocyte developments (e.g., MAST3 and STAB2) and genes involved in macrophage recruitment and regulation of inflammations (PDGFD and PTX3) were suggested as possible causal genes for susceptibility to – and recoverability from mastitis, respectively. However, this is the first GWAS study for recoverability from mastitis and our results need to be validated. The findings in the current study are, therefore, a starting point for further investigations in identifying causal genetic variants or chromosomal regions for both susceptibility to – and recoverability from mastitis.

Bone fracture in egg laying hens is a growing welfare and economic concern in the industry. Although environmental conditions and management (especially nutrition) can exacerbate it, the primary cause of bone weakness and the resulting fractures is believed to have a genetic basis. To test this hypothesis, we performed a genome-wide association study to identify the loci associated with bone strength in laying hens. Genotype and phenotype data were obtained from 752 laying hens belonging to the same pure line population. These hens were genotyped for 580,961 SNPs, with 232,021 SNPs remaining after quality control. Each of the SNPs were tested for association with tibial breaking strength using the family-based score test for association. A total of 52 SNPs across chromosomes 1, 3, 8, and 16 were significantly associated with tibial breaking strength with the genome-wide significance threshold set as a corrected P value of 10e−5. Based on the local linkage disequilibrium around the significant SNPs, 5 distinct and novel QTLs were identified on chromosomes 1 (2 QTLs), 3 (1 QTL), 8 (1 QTL) and 16 (1 QTL). The strongest association was detected within the QTL region on chromosome 8, with the most significant SNP having a corrected P value of 4e−7. A number of candidate genes were identified within the QTL regions, including the BRD2 gene that is required for normal bone physiology. Bone-related pathways involving some of the genes were also identified including chloride channel activity, which regulates bone reabsorption, and intermediate filament organization, which plays a role in the regulation of bone mass. Our result supports previous studies that suggest that bone strength is highly regulated by genetics. It is therefore possible to reduce bone fractures in laying hens through genetic selection and ultimately improve hen welfare.

Mastitis in dairy cows is an unavoidable problem and variation in recovery from mastitis is therefore of interest, in addition to resistance to mastitis. Genetic parameters for mastitis resistance and recovery were estimated for Danish Holstein-Friesian cows using data from Automatic Milking Systems equipped with online somatic cell count (OCC) measuring units. The OCC measurements were converted to elevated mastitis risks (EMR), a continuous variable (on a [0-1] scale) indicating the risk of mastitis. EMR values above 0.6 were assumed to indicate that a cow had mastitis. For each cow and lactation the sequence of health states (mastitic or healthy) was converted to weekly transitions: 0 if the cow stayed within the same state and 1 if the cow changed state. The result was two series of transitions: one for healthy to diseased (HD, to model mastitis resistance) and the other for diseased to healthy (DH, to model recovery). The two series of transitions were analyzed with a bivariate threshold model including a linear combination of systematic effects and of a function of time. The model included effects of herd and parity, herd-test-week, permanent environment (to account for the repetitive nature of transition records from a cow) plus two time-varying effects (lactation stage and time within episode). In early lactation, there was an increased risk of getting mastitis but the risk remained stable afterwards. Mean recovery rate was 45.7%. Posterior mean of correlations between the traits were -0.853 (PSD=0.108), -0.909 (PSD=0.076), -0.292 (PSD=0.105) and 0.052 (PSD=0.157) for the random effects of genetic, permanent environment, cow-parity interaction, and herd-test-week, respectively. Heritabilities were 0.080 (PSD=0.026) for HD and 0.075 (PSD=0.030) for DH. Recovery could be considered as a new trait for selection even though the negative correlation suggests that a cow that easily contracts mastitis has greater difficulty to recover.

Non-coagulating (NC) milk, defined as milk not coagulating within 40 min after rennet-addition, can have a negative influence on cheese production. Its prevalence is estimated at 18% in the Swedish Red (SR) cow population. Our study aimed at identifying genomic regions and causal variants associated with NC milk in SR cows, by doing a GWAS using 777k SNP genotypes and using imputed sequences to fine map the most promising genomic region. Phenotypes were available from 382 SR cows belonging to 21 herds in the south of Sweden, from which individual morning milk was sampled. NC milk was treated as a binary trait, receiving a score of one in case of non-coagulation within 40 min. For all 382 SR cows, 777k SNP genotypes were available as well as the combined genotypes of the genetic variants of αs1-β-κ-caseins. In addition, whole–genome sequences from the 1000 Bull Genome Consortium (Run 3) were available for 429 animals of 15 different breeds. From these sequences, 33 sequences belonged to SR and Finish Ayrshire bulls with a large impact in the SR cow population. Single-marker analyses were run in ASReml using an animal model. After fitting the casein loci, 14 associations at −Log10(P-value) > 6 identified a promising region located on BTA18. We imputed sequences to the 382 genotyped SR cows using Beagle 4 for half of BTA18, and ran a region-wide association study with imputed sequences. In a seven mega base-pairs region on BTA18, our strongest association with NC milk explained almost 34% of the genetic variation in NC milk. Since it is possible that multiple QTL are in strong LD in this region, 59 haplotypes were built, genetically differentiated by means of a phylogenetic tree, and tested in phenotype-genotype association studies. Haplotype analyses support the existence of one QTL underlying NC milk in SR cows. A candidate gene of interest is the VPS35 gene, for which one of our strongest association is an intron SNP in this gene. The VPS35 gene belongs to the mammary gene sets of pre-parturient and of lactating cows.

Genomic selection is a promising development in agriculture, aiming improved production by exploiting molecular genetic markers to design novel breeding programs and to develop new markers-based models for genetic evaluation. It opens opportunities for research, as novel algorithms and lab methodologies are developed. Genomic selection can be applied in many breeds and species. Further research on the implementation of genomic selection in breeding programs is highly desirable not only for the common good, but also the private sector (breeding companies). It has been projected that this approach will improve selection routines, especially in species with long reproduction cycles, late or sex-limited or expensive trait recording and for complex traits. The task of integrating genomic selection into existing breeding programs is, however, not straightforward. Despite successful integration into breeding programs for dairy cattle, it has yet to be shown how much emphasis can be given to the genomic information and how much additional phenotypic information is needed from new selection candidates. Genomic selection is already part of future planning in many breeding companies of pigs and beef cattle among others, but further research is needed to fully estimate how effective the use of genomic information will be for the prediction of the performance of future breeding stock. Genomic prediction of production in crossbreeding and across-breed schemes, costs and choice of individuals for genotyping are reasons for a reluctance to fully rely on genomic information for selection decisions. Breeding objectives are highly dependent on the industry and the additional gain when using genomic information has to be considered carefully. This review synthesizes some of the suggested approaches in selected livestock species including cattle, pig, chicken and fish. It outlines tasks to help understanding possible consequences when applying genomic information in breeding scenarios.

Androstenone and skatole accumulate in the fat of mature non- castrated male pigs and is detected as boar taint - an offensive odour affecting the smell and taste of cooked pork. Genetic variation exists for their concentrations and so selection may provide a more sustainable solution than castration for reducing taint in commercial pigs. Genetic progress is limited by the inability to measure taint prior to selection in young animals. The study objectives were to investigate the potential value of genomic selection methodology for predicting breeding values of androstenone and skatole within a commercial Danish Landrace population. Five hundred male pigs with high skatole (>0.3 μg/g) at slaughter were matched with low skatole male litter mates and measured for androstenone. Phenotypes for both traits were corrected for farm as a fixed effect and age as a covariate prior to genetic analysis. Genotyping was performed using the Illumina SNP60 porcine beadchip. After QC (call rate >0.95, MAF >0.01), 42, 916 SNPs and 938 individuals remained. A 5- fold cross- validation study (~751 training and ~187 validation animals per group) was carried out to compare the accuracy of GBLUP, Bayes A, Bayes SSVS and Bayesian Lasso to predict the unobserved phenotypes. Accuracy was calculated as the correlation between the estimated genomic breeding value and phenotype of validation animals. The range of accuracies obtained by different methods was narrow for androstenone, between 0.29 (Bayes SSVS) and 0.30 (Bayes A), but wider for skatole, between 0.21 (GBLUP) and 0.26 (Bayes SSVS). Relative accuracies corrected for h2, were 0.55- 0.56 and 0.77-0.96 for androstenone and skatole respectively, although these are biased by the selection of the cases and controls. Increasing the size of the training set should further improve genomic prediction, especially for androstenone. The results demonstrate that genomic selection has great potential for reducing boar taint in commercial pigs.

This study focused on haplotype effects and linkage disequilibrium (LD) for the K232A locus and the promoter VNTR in the DGAT1 gene. Analyses were carried out in three German Holstein Frisian populations (including 492, 305, and 518 animals) for milk yield, milk fat and protein yield, and milk fat and protein content. We found that effects of the promoter VNTR were not significant and explain only a small amount of the variation of the QTL on BTA14. Haplotype effects were less significant than the K232A locus by itself, but the haplotype containing the A allele of the K232A locus and allele 3 with five repeats of the promoter VNTR showed negative effects on protein content when paternally inherited, whereas the haplotype with the A allele and VNTR allele 2 (with six repeats) increased the protein content. Significant differences between these two haplotypes occurred for protein yield as well, pointing to a linked effect that is picked up by the haplotypes rather than a direct effect of the VNTR. The linkage disequilibrium, estimated by D', showed values between 0.29 and 0.59 which is unexpectedly low for a distance of similar to 10kb. Only a very low correlation between the two loci was observed due to the almost similar frequencies of haplotypes containing the A or K allele of the K232A locus.

As part of the QTLMAS XII workshop, a simulated dataset was distributed and participants were invited to submit analyses of the data based on genome-wide association, fine mapping and genomic selection. We have evaluated the findings from the groups that reported fine mapping and genome-wide association (GWA) efforts to map quantitative trait loci (QTL). Generally the power to detect QTL was high and the Type 1 error was low. Estimates of QTL locations were generally very accurate. Some methods were much better than others at estimating QTL effects, and with some the accuracy depended on simulated effect size or minor allele frequency. There were also indications of bias in the effect estimates. No epistasis was simulated, but the two studies that included searches for epistasis reported several interacting loci, indicating a problem with controlling the Type I error rate in these analyses. Although this study is based on a single dataset, it indicates that there is a need to improve fine mapping and GWA methods with respect to estimation of genetic effects, appropriate choice of significance thresholds and analysis of epistasis As part of the QTLMAS XII workshop, a simulated dataset was distributed and participants were invited to submit analyses of the data based on genome-wide association, fine mapping and genomic selection. We have evaluated the findings from the groups that reported fine mapping and genome-wide association (GWA) efforts to map quantitative trait loci (QTL). Generally the power to detect QTL was high and the Type 1 error was low. Estimates of QTL locations were generally very accurate. Some methods were much better than others at estimating QTL effects, and with some the accuracy depended on simulated effect size or minor allele frequency. There were also indications of bias in the effect estimates. No epistasis was simulated, but the two studies that included searches for epistasis reported several interacting loci, indicating a problem with controlling the Type I error rate in these analyses. Although this study is based on a single dataset, it indicates that there is a need to improve fine mapping and GWA methods with respect to estimation of genetic effects, appropriate choice of significance thresholds and analysis of epistasis

A dataset was simulated and distributed to participants of the QTLMAS XII workshop who were invited to develop genomic selection models. Each contributing group was asked to describe the model development and validation as well as to submit genomic predictions for three generations of individuals, for which they only knew the genotypes. The organisers used these genomic predictions to perform the final validation by comparison to the true breeding values, which were known only to the organisers. Methods used by the 5 groups fell in 3 classes 1) fixed effects models 2) BLUP models, and 3) Bayesian MCMC based models. The Bayesian analyses gave the highest accuracies, followed by the BLUP models, while the fixed effects models generally had low accuracies and large error variance. The best BLUP models as well as the best Bayesian models gave unbiased predictions. The BLUP models are clearly sensitive to the assumed SNP variance, because they do not estimate SNP variance, but take the specified variance as the true variance. The current comparison suggests that Bayesian analyses on haplotypes or SNPs are the most promising approach for Genomic selection although the BLUP models may provide a computationally attractive alternative with little loss of efficiency. On the other hand fixed effect type models are unlikely to provide any gain over traditional pedigree indexes for selection A dataset was simulated and distributed to participants of the QTLMAS XII workshop who were invited to develop genomic selection models. Each contributing group was asked to describe the model development and validation as well as to submit genomic predictions for three generations of individuals, for which they only knew the genotypes. The organisers used these genomic predictions to perform the final validation by comparison to the true breeding values, which were known only to the organisers. Methods used by the 5 groups fell in 3 classes 1) fixed effects models 2) BLUP models, and 3) Bayesian MCMC based models. The Bayesian analyses gave the highest accuracies, followed by the BLUP models, while the fixed effects models generally had low accuracies and large error variance. The best BLUP models as well as the best Bayesian models gave unbiased predictions. The BLUP models are clearly sensitive to the assumed SNP variance, because they do not estimate SNP variance, but take the specified variance as the true variance. The current comparison suggests that Bayesian analyses on haplotypes or SNPs are the most promising approach for Genomic selection although the BLUP models may provide a computationally attractive alternative with little loss of efficiency. On the other hand fixed effect type models are unlikely to provide any gain over traditional pedigree indexes for selection

The aim of this paper was to describe, and when possible compare, the multivariate methods used by the participants in the EADGENE WP1.4 workshop. The first approach was for class discovery and class prediction using evidence from the data at hand. Several teams used hierarchical clustering (HC) or principal component analysis (PCA) to identify groups of differentially expressed genes with a similar expression pattern over time points and infective agent (E. coli or S. aureus). The main result from these analyses was that HC and PCA were able to separate tissue samples taken at 24 h following E. coli infection from the other samples. The second approach identified groups of differentially co-expressed genes, by identifying clusters of genes highly correlated when animals were infected with E. coli but not correlated more than expected by chance when the infective pathogen was S. aureus. The third approach looked at differential expression of predefined gene sets. Gene sets were defined based on information retrieved from biological databases such as Gene Ontology. Based on these annotation sources the teams used either the GlobalTest or the Fisher exact test to identify differentially expressed gene sets. The main result from these analyses was that gene sets involved in immune defence responses were differentially expressed

International audience; Abstract – Microarray analyses have become an important tool in animal genomics. While their use is becoming widespread, there is still a lot of ongoing research regarding the analysis of microarray data. In the context of a European Network of Excellence, 31 researchers representing 14 research groups from 10 countries performed and discussed the statistical analysesof real and simulated 2-colour microarray data that were distributed among participants. The real data consisted of 48 microarrays from a disease challenge experiment in dairy cattle, while the simulated data consisted of 10 microarrays from a direct comparison of two treatments (dye-balanced). While there was broader agreement with regards to methods of microarray normalisation and significance testing, there were major differences with regards to quality control.The quality control approaches varied from none, through using statistical weights, to omitting a large number of spots or omitting entire slides. Surprisingly, these very different approaches gave quite similar results when applied to the simulated data, although not all participating groups analysed both real and simulated data. The workshop was very successful in facilitating interaction between scientists with a diverse background but a common interest in microarray analyses.

The subject area for this thesis is detection of chromosomal regions or QTL causing complex variation at the phenotypic level. In particular, the differentiation of sources of additive and non additive variation. Unlike QTL mapping using divergent or inbred lines, this study aims to explore methods within populations, facilitating direct application of techniques such as marker assisted selection. Specifically, objectives were to evaluate a linear model or variance components (VC) approach to explore the existence and magnitude of variation caused by additive, dominant and imprinted QTL segregating in general pedigrees. This has been achieved by combining extensive simulation and analysis of real commercial poultry data. Linear models were constructed to simultaneously estimate fixed, polygenic and QTL effects. Different genetic models were compared by hierarchical extension to incorporate more variance components, and likelihood ratio test statistics derived from the comparison of full with reduced or null models. A range of additive, dominant and imprinted QTL effects were simulated within two-generation poultry, pig and human type pedigrees. Effects of family size and structure on power, accuracy of variance component estimation, and distribution of the test statistic, were evaluated. Empirical thresholds were derived by simulating populations under the null hypotheses for each type of simulated pedigree and permutation analysis in real data. In the commercial poultry data, dominant and imprinted QTL effects were found for bodyweight and conformation score. Under simulation, although power to detect QTL effects was high in two-generation livestock pedigrees, considerable variation was found in power and behaviour of test statistics. Power to detect dominance was greater in pig and poultry than human type pedigrees with theoretical thresholds increasingly conservative as the number of dams per sire decreased, highlighting the need for empirical derivation of the critical test statistic. The detection of variance caused by imprinted genes and in particular estimates of variance components were also heavily dependent upon the number of sire and dam families used to estimate them. Results showed that VC analysis can be used to routinely detect genetic effects including imprinting and dominance in complex pedigrees. The work presented is the most extensive evaluation of the detection of non additive QTL using VC methods to date. Results challenge standard assumptions made about power and null distributions and show that optimal use of methodology is dependent on pedigree structure.