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New Approach to the Reduction of Disease-related Piglet Mortality

04 April 2014

Pigs often carry a particular kind of genetic variation that affects their survival and health. Scientists from Aarhus University in Denmark have developed a genetic tool that should make it possible to breed the way out of the problem.

Scientists have found gene variants in Danish pigs that have a negative effect on the pigs' immunity. [Photo: Janne Hansen]

Now there is yet another handle to turn in the fight against piglet mortality, which in Denmark is as high as 22 to 33 per cent of the piglets born, depending on whether we are talking about conventional or organic production. Up to 20 per cent of total piglet mortality is due to disease.

Scientists from Aarhus University have found that a large proportion of the pigs used for breeding in Denmark carry genetic variants that adversely affect their resistance to disease. However, the same scientists also deliver some good news: they have developed a genetic tool that can identify pigs with the adverse gene variants relatively easily. Moreover, this tool is cheaper than the tools hitherto used.

If the experimental results can be transferred to practical use, pig breeders will be able to weed out pigs with unwanted gene variants before they are used as parents for future generations. The expectation is that the removal of the ‘bad’ variants from the gene pool will help reduce the use of antibiotics in swine herds without compromising pig welfare, the farmer’s profits, or the health of the consumer.

"We have developed a genetic tool that can identify the animals’ MBL genotypes. This means that we are able to locate the genetic variations that affect the production of MBL in a negative direction," explains senior scientist Helle R. Juul-Madsen from Aarhus University.

But why is knowledge of the pigs’ genotypes so interesting in connection with MBL? And what exactly is MBL? Hold on tight, for now we take a journey into the inner sanctuary of the body, right into the cells where proteins are produced.

The Code of a Protein

The production of proteins in the body takes place in the cells, where a code for each protein is read from our DNA. DNA is made up of four kinds of chemical bases. These constitute a kind of alphabet consisting of four letters.

The ‘letters’ form ‘words’, and these words, in turn, form the blueprint for production of the protein. The catch is that the ‘words’ always have to consist of three ‘letters’. Correct deciphering of the code therefore requires that the DNA code always is divisible by three.

MBL (mannose-binding lectin) is a protein found primarily in the blood, but MBL is also produced locally in tissue, e.g., the lungs and intestines, and carries out its function there. If you have too little MBL, this will affect the immune system in a negative direction. The less MBL you have, the more likely it is that you become sick from infectious microorganisms. This applies equally to humans, pigs, and other animals.

Unlike humans, pigs produce two kinds of MBL. These proteins are called MBL-A and MBL-C and contribute significantly to the maintenance of a healthy immune system.

Production Glitch

The scientists have found that there are several versions of the A and C genes, and that some variants mess up the production of MBL. The production may be affected in two ways: either such that insufficient amounts of MBL are produced, or such that the MBL that is produced is nonfunctional. For the A gene, a particular error in the middle of the gene affects the amounts of MBL-A produced in the body. Dr Juul-Madsen has previously described variations in the A gene and their effect on the immune system in pigs (Reduction in pig medicine usage is plausible).

Now she has turned her attention to the C gene and found several different variations that cause defects in the amounts of MBL-C produced. In addition, she found a special variant that affects the formation of functional MBL-C. This is because the code of this variant is not divisible by three. In the middle of the gene, two ‘letters’ are missing, which means that the code is not deciphered properly and the ‘words’ translated into pure gibberish. The result is that only nonfunctional MBL-C protein is formed.

It can go even more wrong if you have a combination of two ‘bad’ variants, i.e., a ‘bad’ C gene, that either does not produce enough MBL or produces nonfunctional MBL, and a ‘bad’ A gene, that generates too little MBL. This unfortunate combination has been found by Dr Juul-Madsen and her colleagues in a large proportion of the Danish pigs studied.

Unlucky Genes

The scientists analysed a selection of Danish Landrace and Duroc pigs. They recorded whether the pigs had a ‘bad’ A gene and a ‘good’ C gene, a ‘bad’ C gene and a ‘good’ A gene, or both a ‘bad’ A gene and a ‘bad’ C gene.

Thirty-three per cent of the Landrace pigs were carriers of gene variant that are likely to produce both too little A and nonfunctional C. This will cause immunosuppression. More than half of the Landrace pigs – 55 per cent – were carriers of the gene variant that results in nonfunctional C, whilst this was true for as much as 90 per cent of the Durocs.

The mother of a Danish production pig is usually a cross between Landrace and Yorkshire while the father is a Duroc. This means that the production pigs are ½ Duroc, ¼ Landrace and ¼ Yorkshire. Three-quarters of their genetic material therefore comes from parental material with a high frequency of A and C gene variants that lack a code for an optimal quantity and/or quality of MBL.

The scientists also studied a Belgian Pietrain cross. Here they found that only two per cent of the animals carried the gene variant with the double dose of ‘bad’ A and C genes. In addition, they also discovered two beneficial variants not found in the Danish pigs. Pietrain pigs with the ‘good’ genes on both chromosomes weighed significantly more at weaning than pigs that had either a ‘bad’ A gene or a ‘bad’ C gene, or two ‘bad’ genes on one chromosome.

It is not yet known how the genotypes of the Yorkshire breed code for MBL production.

"At this stage, we cannot rule out that the Danish pigs and their MBL production is partially saved by the genes of the Yorkshire breed," says Helle R. Juul-Madsen. "We also still need to show that the experimental results can be reproduced under practical Danish conditions."

MBL and Robustness

A low or ‘bad’ MBL status is not a problem only for Danish pigs. A Canadian study has reported ‘bad’ A and C variants in Canadian pigs as well. The Canadian scientists found that ‘bad’ or low MBL levels is associated with a higher incidence of diseases such as pneumonia, diarrhoea, pleurisy, endocarditis and septicaemia, and that the animals’ general immune response against viral and bacterial diseases was impaired. The frequency of ‘bad’ A or C genes was significantly higher in sick pigs compared with healthy animals.

Dr Juul-Madsen has previously shown that chickens with high MBL levels are more robust than chickens with low MBL levels. Other studies have shown that in humans, there is a correlation between low MBL levels and recurrent abortions, premature births, low birthweight and weaker resistance against disease. It would undoubtedly also be interesting to investigate these aspects in relation to piglet mortality.

The results of the study are published in the scientific journal, Immunogenetics, with the title A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs.

The research is partly funded by the Ministry of Food, Agriculture and Fisheries under its agreement with Aarhus University.

April 2014

Aarhus University

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