The influence of selective breeding on MHC diversity
Issued: Thu, 03 Jul 2014 12:28:00 BST
Livestock industries are starting to use genomic breeding values (GEBV) to identify superior animals. Directional selection then increases the frequency of the genes that contribute to the GEBV. However, some polymorphisms are balanced and here directional selection could paradoxically increase disease susceptibility.
The most important genetic region contributing to disease resistance is the Major Histocompatibility Complex; this is the most variable region of the genome and this variation is maintained by balancing selection. However, we do not fully understand how balancing selection on the MHC works. We have compared different forms of balancing selection by mathematical modelling and our preliminary results suggest that divergent allele advantage is the main driver of MHC polymorphism. The divergent allele hypothesis makes specific predictions about the behaviour of MHC alleles in response to selection for disease resistance. In particular, heterozygosity should be maintained although the frequency of individual alleles may change.
We propose to examine a flock of sheep that has been successfully selected for increased resistance to nematode infection. This flock of sheep contains 500 breeding ewes and has been selected for reduced faecal egg count over 25 years. We have access to DNA from the founder and current lamb populations and propose to test whether MHC genotype frequencies have changed in agreement with the divergent allele or alternative hypotheses.
Once we understand how selection maintains MHC diversity we will develop breeding schemes based that utilise MHC variation in a sustainable way to improve resistance to disease. These breeding schemes will utilise GEBV and incorporate all polymorphisms known to increase economically important traits including disease resistance and fertility. By replicating the selective forces that maintain MHC variation, we expect to increase disease resistance in a sustainable and effective way.