Genomic prediction in an admixed population of Atlantic salmon (Salmo salar)

Reliability of genomic selection (GS) models was tested in an admixed population of Atlantic salmon, originating from crossing of several wild subpopulations. The models included ordinary genomic BLUP models (GBLUP), using genome-wide SNP markers of varying densities (1 to 220k), a genomic identity-by-descent model (IBD-GS), using linkage analysis of sparse genome-wide markers, as well as a classical pedigree-based model. Reliabilities of the models were compared through 5-fold cross-validation. The traits studied were salmon lice (Lepeophtheirus salmonis) resistance (LR), measured as (log) density on the skin and fillet color (FC), with respective estimated heritabilities of 0.14 and 0.43. All genomic models outperformed the classical pedigree-based model, for both traits and at all marker densities. However, the relative improvement differed considerably between traits, models and marker densities. For the highly heritable FC, the IBD-GS had similar reliability as GBLUP at high marker densities (>22k). In contrast, for the lowly heritable LR, IBD-GS was clearly inferior to GBLUP, irrespective of marker density. Hence, GBLUP was robust to marker density for the lowly heritable LR, but sensitive to marker density for the highly heritable FC. We hypothesize that this phenomenon may be explained by historical admixture of different founder populations, expected to reduce short-range LD and induce long-range LD. The relative importance of LD/relationship information is expected to decrease/increase with increasing heritability of the trait. Still, using the ordinary GBLUP, the typical long-range LD of an admixed population may be effectively captured by sparse markers, while efficient utilization of relationship information may require denser markers (e.g., 22k or more)

Estimation of heritability from limited family data using genome-wide identity-by-descent sharing

<p>Abstract</p> <p>Background</p> <p>In classical pedigree-based analysis, additive genetic variance is estimated from between-family variation, which requires the existence of larger phenotyped and pedigreed populations involving numerous families (parents). However, estimation is often complicated by confounding of genetic and environmental family effects, with the latter typically occurring among full-sibs. For this reason, genetic variance is often inferred based on covariance among more distant relatives, which reduces the power of the analysis. This simulation study shows that genome-wide identity-by-descent sharing among close relatives can be used to quantify additive genetic variance solely from within-family variation using data on extremely small family samples.</p> <p>Methods</p> <p>Identity-by-descent relationships among full-sibs were simulated assuming a genome size similar to that of humans (effective number of loci ~80). Genetic variance was estimated from phenotypic data assuming that genomic identity-by-descent relationships could be accurately re-created using information from genome-wide markers. The results were compared with standard pedigree-based genetic analysis.</p> <p>Results</p> <p>For a polygenic trait and a given number of phenotypes, the most accurate estimates of genetic variance were based on data from a single large full-sib family only. Compared with classical pedigree-based analysis, the proposed method is more robust to selection among parents and for confounding of environmental and genetic effects. Furthermore, in some cases, satisfactory results can be achieved even with less ideal data structures, i.e., for selectively genotyped data and for traits for which the genetic variance is largely under the control of a few major genes.</p> <p>Conclusions</p> <p>Estimation of genetic variance using genomic identity-by-descent relationships is especially useful for studies aiming at estimating additive genetic variance of highly fecund species, using data from small populations with limited pedigree information and/or few available parents, i.e., parents originating from non-pedigreed or even wild populations.</p

The power to detect artificial selection acting on single loci in recently domesticated species

<p>Abstract</p> <p>Background</p> <p>An increasing number of aquaculture species are subjected to artificial selection in systematic breeding programs. Rapid improvements of important commercial traits are reported, but little is known about the effects of the strong directional selection applied, on gene level variation. Large numbers of genetic markers are becoming available, making it feasible to detect and estimate these effects. Here a simulation tool was developed in order to explore the power by which single genetic loci subjected to uni-directional selection in parallel breeding populations may be detected.</p> <p>Findings</p> <p>Two simulation models were pursued: 1) screening for loci displaying higher genetic differentiation than expected (high-F_SToutliers), from neutral evolution between a pool of domesticated populations and a pool of wild populations; 2) screening for loci displaying lower genetic differentiation (low-F_SToutliers) between domesticated strains than expected from neutral evolution. The premise for both approaches was that the isolated domesticated strains are subjected to the same breeding goals. The power to detect outlier loci was calculated under the following parameter values: number of populations, effective population size per population, number of generations since onset of selection, initial F_ST, and the selection coefficient acting on the locus. Among the parameters investigated, selection coefficient, the number of generation since onset of selection, and number of populations, had the largest impact on power. The power to detect loci subjected to directional in breeding programmes was high when applying the between farmed and wild population approach, and low for the between farmed populations approach.</p> <p>Conclusions</p> <p>A simulation tool was developed for estimating the power to detect artificial selection acting directly on single loci. The simulation tool should be applicable to most species subject to domestication, as long as a reasonable high accuracy in input parameters such as effective population size, number of generations since the initiation of selection, and initial differentiation (F_ST) can be obtained. Identification of genetic loci under artificial selection would be highly valuable, since such loci could be used to monitor maintenance of genetic variation in the breeding populations and monitoring possible genetic changes in wild populations from genetic interaction between escapees and their wild counterpart.</p

Mapping of quantitative trait loci for flesh colour and growth traits in Atlantic salmon (Salmo salar)

<p>Abstract</p> <p>Background</p> <p>Flesh colour and growth related traits in salmonids are both commercially important and of great interest from a physiological and evolutionary perspective. The aim of this study was to identify quantitative trait loci (QTL) affecting flesh colour and growth related traits in an F2 population derived from an isolated, landlocked wild population in Norway (Byglands Bleke) and a commercial production population.</p> <p>Methods</p> <p>One hundred and twenty-eight informative microsatellite loci distributed across all 29 linkage groups in Atlantic salmon were genotyped in individuals from four F2 families that were selected from the ends of the flesh colour distribution. Genotyping of 23 additional loci and two additional families was performed on a number of linkage groups harbouring putative QTL. QTL analysis was performed using a line-cross model assuming fixation of alternate QTL alleles and a half-sib model with no assumptions about the number and frequency of QTL alleles in the founder populations.</p> <p>Results</p> <p>A moderate to strong phenotypic correlation was found between colour, length and weight traits. In total, 13 genome-wide significant QTL were detected for all traits using the line-cross model, including three genome-wide significant QTL for flesh colour (Chr 6, Chr 26 and Chr 4). In addition, 32 suggestive QTL were detected (chromosome-wide P < 0.05). Using the half-sib model, six genome-wide significant QTL were detected for all traits, including two for flesh colour (Chr 26 and Chr 4) and 41 suggestive QTL were detected (chromosome-wide P < 0.05). Based on the half-sib analysis, these two genome-wide significant QTL for flesh colour explained 24% of the phenotypic variance for this trait.</p> <p>Conclusions</p> <p>A large number of significant and suggestive QTL for flesh colour and growth traits were found in an F2 population of Atlantic salmon. Chr 26 and Chr 4 presented the strongest evidence for significant QTL affecting flesh colour, while Chr 10, Chr 5, and Chr 4 presented the strongest evidence for significant QTL affecting growth traits (length and weight). These QTL could be strong candidates for use in marker-assisted selection and provide a starting point for further characterisation of the genetic components underlying flesh colour and growth.</p

The genetic architecture of growth and fillet traits in farmed Atlantic salmon (Salmo salar)

BACKGROUND: Performance and quality traits such as harvest weight, fillet weight and flesh color are of economic importance to the Atlantic salmon aquaculture industry. The genetic factors underlying these traits are of scientific and commercial interest. However, such traits are typically polygenic in nature, with the number and size of QTL likely to vary between studies and populations. The aim of this study was to investigate the genetic basis of several growth and fillet traits measured at harvest in a large farmed salmon population by using SNP markers. Due to the marked heterochiasmy in salmonids, an efficient two-stage mapping approach was applied whereby QTL were detected using a sire-based linkage analysis, a sparse SNP marker map and exploiting low rates of recombination, while a subsequent dam-based analysis focused on the significant chromosomes with a denser map to confirm QTL and estimate their position. RESULTS: The harvest traits all showed significant heritability, ranging from 0.05 for fillet yield up to 0.53 for the weight traits. In the sire-based analysis, 1695 offspring with trait records and their 20 sires were successfully genotyped for the SNPs on the sparse map. Chromosomes 13, 18, 19 and 20 were shown to harbor genome-wide significant QTL affecting several growth-related traits. The QTL on chr. 13, 18 and 20 were detected in the dam-based analysis using 512 offspring from 10 dams and explained approximately 6–7 % of the within-family variation in these traits. CONCLUSIONS: We have detected several QTL affecting economically important complex traits in a commercial salmon population. Overall, the results suggest that the traits are relatively polygenic and that QTL tend to be pleiotropic (affecting the weight of several components of the harvested fish). Comparison of QTL regions across studies suggests that harvest trait QTL tend to be relatively population-specific. Therefore, the application of marker or genomic selection for improvement in these traits is likely to be most effective when the discovery population is closely related to the selection candidates (e.g. within-family genomic selection). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0215-y) contains supplementary material, which is available to authorized users

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Stability in Ecosystem Functioning across a Climatic Threshold and Contrasting Forest Regimes

Classical ecological theory predicts that changes in the availability of essential resources such as nitrogen should lead to changes in plant community composition due to differences in species-specific nutrient requirements. What remains unknown, however, is the extent to which climate change will alter the relationship between plant communities and the nitrogen cycle. During intervals of climate change, do changes in nitrogen cycling lead to vegetation change or do changes in community composition alter the nitrogen dynamics? We used long-term ecological data to determine the role of nitrogen availability in changes of forest species composition under a rapidly changing climate during the early Holocene (16k to 8k cal. yrs. BP). A statistical computational analysis of ecological data spanning 8,000 years showed that secondary succession from a coniferous to deciduous forest occurred independently of changes in the nitrogen cycle. As oak replaced pine under a warming climate, nitrogen cycling rates increased. Interestingly, the mechanism by which the species interacted with nitrogen remained stable across this threshold change in climate and in the dominant tree species. This suggests that changes in tree population density over successional time scales are not driven by nitrogen availability. Thus, current models of forest succession that incorporate the effects of available nitrogen may be over-estimating tree population responses to changes in this resource, which may result in biased predictions of future forest dynamics under climate warming

Mapping and validation of a major QTL affecting resistance to pancreas disease (salmonid alphavirus) in Atlantic salmon (Salmo salar)

Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large negative economic and animal welfare impact on Atlantic salmon aquaculture. Evidence for genetic variation in host resistance to this disease has been reported, suggesting that selective breeding may potentially form an important component of disease control. The aim of this study was to explore the genetic architecture of resistance to PD, using survival data collected from two unrelated populations of Atlantic salmon; one challenged with SAV as fry in freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP 2). Analyses of the binary survival data revealed a moderate-to-high heritability for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP 2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide polymorphism markers, and six putative resistance quantitative trait loci (QTL) were identified. One of these QTL was mapped to the same location on chromosome 3 in both populations, reaching chromosome-wide significance in both the sire- and dam-based analyses in POP 1, and genome-wide significance in a combined analysis in POP 2. This independently verified QTL explains a significant proportion of host genetic variation in resistance to PD in both populations, suggesting a common underlying mechanism for genetic resistance across lifecycle stages. Markers associated with this QTL are being incorporated into selective breeding programs to improve PD resistance

Exploring genetic resistance to infectious salmon anaemia virus in Atlantic salmon by genome-wide association and RNA sequencing

Funding The authors gratefully acknowledge funding from BBSRC (BB/R008612/1, BB/R008973/1), in addition to BBSRC Institute Strategic Programme Grants to the Roslin Institute (BB/P013759/1 and BB/P013740/1).Peer reviewedPublisher PD

Genetic Resistance to Rhabdovirus Infection in Teleost Fish Is Paralleled to the Derived Cell Resistance Status

Genetic factors of resistance and predisposition to viral diseases explain a significant part of the clinical variability observed within host populations. Predisposition to viral diseases has been associated to MHC haplotypes and T cell immunity, but a growing repertoire of innate/intrinsic factors are implicated in the genetic determinism of the host susceptibility to viruses. In a long-term study of the genetics of host resistance to fish rhabdoviruses, we produced a collection of double-haploid rainbow trout clones showing a wide range of susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) waterborne infection. The susceptibility of fibroblastic cell lines derived from these clonal fish was fully consistent with the susceptibility of the parental fish clones. The mechanisms determining the host resistance therefore did not associate with specific host immunity, but rather with innate or intrinsic factors. One cell line was resistant to rhabdovirus infection due to the combination of an early interferon IFN induction - that was not observed in the susceptible cells - and of yet unknown factors that hamper the first steps of the viral cycle. The implication of IFN was well consistent with the wide range of resistance of this genetic background to VSHV and IHNV, to the birnavirus IPNV and the orthomyxovirus ISAV. Another cell line was even more refractory to the VHSV infection through different antiviral mechanisms. This collection of clonal fish and isogenic cell lines provides an interesting model to analyze the relative contribution of antiviral pathways to the resistance to different viruses