Establishing the Missing Pieces for a Breeding Selection Programme: TMEM154 and Maedi Visna Resistance in Sheep

The small ruminant lentiviruses (SRLVs) cause the disease known as Maedi Visna (MV) in sheep. This is an insidious respiratory disease of sheep with severe economic impacts. It is difficult to detect and control due to a very long latent period between infection and testing positive.

Farms often do not realise their animals are affected until over 50% of the flock is infected with a large number of animals thin and dying. There are no treatment or vaccination options and control is dependent on testing and culling affected animals over repeated rounds. The cost of control is prohibitive, and this disease makes heavily infected operations economically unviable.

The disease has been highlighted by the Agriculture and Horticulture Development board (AHDB) as an "iceberg" disease where awareness of disease is low in farmers, hiding the scale and impact on production losses. To make matters worse the incidence of MV is increasing rapidly in the UK flock with prevalence rising from 1.4 % in 1995 to 9.4% in 2019.

Northern Ireland has also experienced a breakdown in its previously MV-free status in 2022 and may not be able to regain it due to the number of flocks and length of time it has gone undetected.

There is a critical need for viable options for protecting commercial flocks from this devastating disease. Breed differences in susceptibility to MV have long been recognised. Recent advances in small ruminant genetics and genomics have enabled the genetic loci responsible for these differences to be described.

There is very strong genetic and epidemiological evidence for the glutamic acid to lysine mutation at amino acid 35 of the TMEM154 (transmembrane protein 154) providing resistance to both infection with and progression of MV. However, there are a number of fundamental things we need to know about the gene and the mutation before we could recommend a genetic selection programme using this marker.

We do not know what this gene actually does in sheep (or any animal), how widespread in UK sheep breeds the resistant allele is, whether there are deleterious effects to the resistance mutation and whether the effectiveness of the MV resistance is dependent on the infecting strain of the virus. This research programme seeks to answer those questions to enable us to be sure we are recommending a safe and effective control option for reducing the impact of MV on UK sheep farms.

The option of genetic selection for disease resistance is a popular one with sheep breeders, particularly as the scrapie elimination programme was very successful giving them a positive experience of genetic selection for disease resistance. The marker concerned is on the current SNP chip array used widely for sheep genetic selection and this programme will help drive uptake of the use of genetic markers in commercial sheep breeding.