Dataset Information

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon.

ABSTRACT: BACKGROUND: Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes can modulate susceptibility to the parasite. In this study, we used quantitative trait locus (QTL) analysis to test the effect of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6, respectively. RESULTS: Significant QTL effects were detected on both LG 6 and LG 15 in sire-based analysis but the QTL regions remained unresolved due to a lack of recombination between markers. In dam-based analysis, a significant QTL was identified on LG 6, which accounted for 12.9% of within-family variance in lice abundance. However, the QTL was located at the opposite end of DAA, with no significant overlap with the MHC class II region. Interestingly, QTL modelling also revealed evidence of sex-linked differences in lice abundance, indicating that males and females may have different susceptibility to infection. CONCLUSION: Overall, QTL analysis provided relatively weak support for a proximal effect of classical MHC regions on lice abundance, which can partly be explained by linkage to other genes controlling susceptibility to L. salmonis on the same chromosome.

SUBMITTER: Gharbi K

PROVIDER: S-EPMC2680909 | biostudies-other | 2009

REPOSITORIES: biostudies-other

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Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon.

Gharbi Karim K Glover Kevin A KA Stone Louise C LC MacDonald Elizabeth S ES Matthews Louise L Grimholt Unni U Stear Michael J MJ

BMC genetics 20090427

<h4>Background</h4>Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes ...[more]

PMID: 19397823

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Project description:BackgroundThe replacement of fish oil (FO) and fishmeal with plant ingredients in the diet of farmed Atlantic salmon has resulted in reduced levels of the health-promoting long-chain polyunsaturated omega-3 fatty acids (n-3 LC-PUFA) eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in their filets. Previous studies showed the potential of selective breeding to increase n-3 LC-PUFA levels in salmon tissues, but knowledge on the genetic parameters for individual muscle fatty acids (FA) and their relationships with other traits is still lacking. Thus, we estimated genetic parameters for muscle content of individual FA, and their relationships with lipid deposition traits, muscle pigmentation, sea lice and pancreas disease in slaughter-sized Atlantic salmon. Our aim was to evaluate the selection potential for increased n-3 LC-PUFA content and provide insight into FA metabolism in Atlantic salmon muscle.ResultsAmong the n-3 PUFA, proportional contents of alpha-linolenic acid (ALA; 18:3n-3) and DHA had the highest heritability (0.26) and EPA the lowest (0.09). Genetic correlations of EPA and DHA proportions with muscle fat differed considerably, 0.60 and 0.01, respectively. The genetic correlation of DHA proportion with visceral fat was positive and high (0.61), whereas that of EPA proportion with lice density was negative. FA that are in close proximity along the bioconversion pathway showed positive correlations with each other, whereas the start (ALA) and end-point (DHA) of the pathway were negatively correlated (- 0.28), indicating active bioconversion of ALA to DHA in the muscle of fish fed high FO-diet.ConclusionsSince contents of individual FA in salmon muscle show additive genetic variation, changing FA composition by selective breeding is possible. Taken together, our results show that the heritabilities of individual n-3 LC-PUFA and their genetic correlations with other traits vary, which indicates that they play different roles in muscle lipid metabolism, and that proportional muscle contents of EPA and DHA are linked to body fat deposition. Thus, different selection strategies can be applied in order to increase the content of healthy omega-3 FAin the salmon muscle. We recommend selection for the proportion of EPA + DHA in the muscle because they are both essential FA and because such selection has no clear detrimental effects on other traits.

Project description:Antigen processing and presentation by major histocompatibility complex (MHC) molecules is a cornerstone in vertebrate immunity. Like mammals, teleosts possess both classical MHC class I and multiple families of divergent MHC class I genes. However, while certain mammalian MHC class I-like molecules have proven to be integral in immune regulation against a broad array of pathogens, the biological relevance of the different MHC class I lineages in fish remains elusive. This work focuses on MHC class I L lineage genes and reveals unique regulatory patterns of six genes (Sasa-lia, Sasa-lda, Sasa-lca, Sasa-lga, Sasa-lha, and Sasa-lfa) in antimicrobial immunity of Atlantic salmon (Salmo salar L.). Using two separate in vivo challenge models with different kinetics and immune pathologies combined with in vitro stimulation using viral and bacterial TLR ligands, we show that de novo synthesis of different L lineage genes is distinctly regulated in response to various microbial stimuli. Prior to the onset of classical MHC class I gene expression, lia was rapidly and systemically induced in vivo by the single-stranded (ss) RNA virus salmonid alpha virus 3 (SAV3) but not in response to the intracellular bacterium Piscirickettsia salmonis. In contrast, lga expression was upregulated in response to both viral and bacterial stimuli. A role for distinct MHC class I L-lineage genes in anti-microbial immunity in salmon was further substantiated by a marked upregulation of lia and lga gene expression in response to type I IFNa stimulation in vitro. Comparably, lha showed no transcriptional induction in response to IFNa stimulation but was strongly induced in response to a variety of viral and bacterial TLR ligands. In sharp contrast, lda showed no response to viral or bacterial challenge. Similarly, induction of lca, which is predominantly expressed in primary and secondary lymphoid tissues, was marginal with the exception of a strong and transient upregulation in pancreas following SAV3 challenge Together, these findings suggest that certain Atlantic salmon MHC class I L lineage genes play important and divergent roles in early anti-microbial response and that their regulation, in response to different activation signals, represents a system for selectively promoting the expression of distinct non-classical MHC class I genes in response to different types of immune challenges.

Project description:BackgroundWe have previously sequenced more than 500 kb of the duplicated MHC class I regions in Atlantic salmon. In the IA region we identified the loci for the MHC class I gene Sasa-UBA in addition to a soluble MHC class I molecule, Sasa-ULA. A pseudolocus for Sasa-UCA was identified in the nonclassical IB region. Both regions contained genes for antigen presentation, as wells as orthologues to other genes residing in the human MHC region.ResultsThe genomic localisation of two MHC class I lineages (Z and S) has been resolved. 7 BACs were sequenced using a combination of standard Sanger and 454 sequencing. The new sequence data extended the IA region with 150 kb identifying the location of one Z-lineage locus, ZAA. The IB region was extended with 350 kb including three new Z-lineage loci, ZBA, ZCA and ZDA in addition to a UGA locus. An allelic version of the IB region contained a functional UDA locus in addition to the UCA pseudolocus. Additionally a BAC harbouring two MHC class I genes (UHA) was placed on linkage group 14, while a BAC containing the S-lineage locus SAA (previously known as UAA) was placed on LG10. Gene expression studies showed limited expression range for all class I genes with exception of UBA being dominantly expressed in gut, spleen and gills, and ZAA with high expression in blood.ConclusionHere we describe the genomic organization of MHC class I loci from the U-, Z-, and S-lineages in Atlantic salmon. Nine of the described class I genes are located in the extension of the duplicated IA and IB regions, while three class I genes are found on two separate linkage groups. The gene organization of the two regions indicates that the IB region is evolving at a different pace than the IA region. Expression profiling, polymorphic content, peptide binding properties and phylogenetic relationship show that Atlantic salmon has only one MHC class Ia gene (UBA), in addition to a multitude of nonclassical MHC class I genes from the U-, S- and Z-lineages.

Dataset Information

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon.

Publications

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon.

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