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Evaluation of MHC genes as quantitative trait loci for disease resistance in fish.

Objective

The objective of this study is to assess the usefulness of highly polymorphic genetic markers, the Major Histocompatibility Complex (MHC) genes, of which it has been firmly established that the molecules they encode are critically involved in the initiation of an adequate immune response to pathogens, as quantities trait loci (QTL) for improving selective breeding.

The Major Histocompatibility Complex surface glycoproteins play an important role in the immune defence of higher vertebrates where they bind and present endogenous (MHC class I molecules) and exogenous (MHC class II molecules) peptides to T cells, thereby triggering a specific immune reaction towards the pathogen, from which the peptides are derived. The exogenous peptides bound by the MHC class II alpha/ MHC class II beta molecule are mainly derived from bacteria, whereas the endogenous peptides bound and presented by the MHC class I molecule are derived from intracellular virus or self proteins. The MHC class I and class II beta genes are highly variable, i.e., there are numerous alleles and numerous haplotypes in a population. Each allele has the ability to bind and present different groups of peptides in more or less successful ways. Thus, the response of an organism towards certain pathogens can be genetically influenced by the MHC haplotype.
The best documented MHC correlation with disease resistance is that in chicken with respect to Marek's disease where they were able to use a large number of experimental animals. Fish is another example of an animal species where large numbers of offspring can be generated, and used in appropriate challenge or selection programs. Several studies have shown that the MHC is indeed highly polymorphic in fish. Moreover, the number of expressed MHC genes of both classes seems to be limited, making molecular haplotyping of fish a feasible undertaking. This project will be the first to address the possibility to assess the usefulness of MHC genes as QTL for disease in fish, using a large number of experimental animals of which heritability estimates for other parameters have already been established. We have designed this project to look for correlations between particular MHC allelels/ haplotypes, and high or low resistance to one bacterial and one viral pathogen in fish. Finding such correlations would enable more specific and therefore more successful breeding programs in future aquaculture. It would also eliminate the breeding companies need to establish and use costly and time-consuming challenge experiments.
The project involves characterisation of both parental and offspring MHC class I, class II alpha and class II beta alleles in a material consisting of 50 dams, 50 sires and their 50 pedigrees. Each pedigrees is challenged with one bacterial and one (two) viral infectious agent(s) and data is collected on death/ survival of each individual. Finally, data on MHC variants and death/ survival are tested by statistical analysis to identify positive or negative correlations to disease resistance.
MHC variants in the parental material are more or less characterised and the challenge tests are done. Remaining tasks are typing of the pedigrees and statistical analysis of the data.
This project mainly focuses on the usefulness of specific DNA markers as QTLs for disease resistance. A side effect is the general knowledge generated on MHC alleles and haplotypes in fish. This far, we have identified 21 MHC class II beta alleles in a material consisting of 50 dams and 50 sires, clearly a large number of alleles for this few individuals originating from one population.
We will shortly finish our analysis on MHC class I and class II alpha variants in the parental material and move on to MHC-typing of the pedigrees. The final statistical analysis is expected to begin in year 2000.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

NORWEGIAN SCHOOL OF VETERINARY SCIENCE
Address
Ullevaalsveien 72
0033 Oslo
Norway

Participants (4)

AGRICULTURAL UNIVERSITY OF WAGENINGEN
Netherlands
Address
Costerweg 50
Wageningen
Akva Gen AS
Norway
Address

6600 Sunndalsora
Akvaforsk - Institute of Aquaculture Research Ltd.
Norway
Address

6600 Sunndalsora
National Centre for Veterinary Contract Research and Commercial Services A/S
Norway
Address
Alhusstrand, Elvalandet
7800 Namsos