Establishing the Missing Pieces for a Breeding Selection Programme: TMEM154 and Maedi Visna Resistance in Sheep
Lead Research Organisation:
MOREDUN RESEARCH INSTITUTE
Department Name: Disease Control
Abstract
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Technical Summary
Maedi Visna is a chronic lentiviral disease of sheep that currently affects just under 10% of the UK flock with concurrent productivity losses of over 8%. The virus is extremely hypervariable and has a long latent phase of months to years between infection and testing positive or displaying disease symptoms.
One control option going forward is selection for genetic resistance to the virus. Multiple large GWAS and targeted field studies have highlighted Transmembrane protein 154 (an E to K change at position 35 and homozygosity for the K allele) as strongly associated with decreased risk of MV and there are increasing calls for the implementation of selection for this allele in sheep breeding programmes.
Before proceeding with recommending and implementing such a programme in the UK however, there are a number of unanswered questions. The first is what the existing TMEM154 alleles are in the UK commercial sheep flock, which will be addressed by genotyping animals from the most common breed combinations in commercial flocks.
The second question is what the actual function of the gene is and whether selecting for MV resistance may inadvertently select for deleterious phenotypes. We do not know what TMEM154 does in any species or how it interacts with the virus. This will be addressed by a range of cell culture experiments with tagged virus and TMEM154 constructs and knockouts in continuous and primary cell lines with downstream phenotypic (cell morphology, survival, virus load and cellular location), transcriptomic and proteomic analysis to elucidate the function of the protein and how it causes resistance to viral infection. These results will be confirmed in naturally infected animals with varying TMEM154 genotypes. This work will be combined with virus genotyping to explore viral genetic selection based on TMEM154 phenotype.
One control option going forward is selection for genetic resistance to the virus. Multiple large GWAS and targeted field studies have highlighted Transmembrane protein 154 (an E to K change at position 35 and homozygosity for the K allele) as strongly associated with decreased risk of MV and there are increasing calls for the implementation of selection for this allele in sheep breeding programmes.
Before proceeding with recommending and implementing such a programme in the UK however, there are a number of unanswered questions. The first is what the existing TMEM154 alleles are in the UK commercial sheep flock, which will be addressed by genotyping animals from the most common breed combinations in commercial flocks.
The second question is what the actual function of the gene is and whether selecting for MV resistance may inadvertently select for deleterious phenotypes. We do not know what TMEM154 does in any species or how it interacts with the virus. This will be addressed by a range of cell culture experiments with tagged virus and TMEM154 constructs and knockouts in continuous and primary cell lines with downstream phenotypic (cell morphology, survival, virus load and cellular location), transcriptomic and proteomic analysis to elucidate the function of the protein and how it causes resistance to viral infection. These results will be confirmed in naturally infected animals with varying TMEM154 genotypes. This work will be combined with virus genotyping to explore viral genetic selection based on TMEM154 phenotype.
