Towards the brave new world of pig genomics

Thursday, April 3, 2014

Developments in pig genomics are helping us identify beneficial characteristics in pigs soon after birth, in particular with respect to pork quality and resistance to PRRSV

by S. ERNEST SANFORD

Genomics is a discipline in genetics that uses molecular biology technology such as DNA sequencing, recombinant DNA and bioinformatics methods to sequence, assemble and analyze the function and structure of an animal's genome.

The genome is the complete set of DNA that is present in any living being, including animals, plants and humans. With knowledge of an animal's complete genome, the structure and function of biological functions can be accurately mapped and predicted with a high degree of accuracy from a very early age, soon after birth or even as a fetus in utero.

The human genome was sequenced and published in draft form for one person by the Human Genome Project Team in early 2001 and finalized in 2007 after sequencing of many other individuals.

The Pig Genome Sequencing Project, started in 2003, gathered momentum after 2006 and was completed in draft form in November 2009. Sequencing was of a Duroc sow from Illinois.

Once sequencing of the entire pig genome was done, it was immediately obvious that it would have a major impact on many aspects of the pig's life, including:

• Nutrition, via genes involved in digestion of certain feedstuffs;
• Carcass quality, via genes involved in lean content and intramuscular fat deposits;
• Health, via genes involved in immune response to certain disease agents (pathogens) and formulation of design of novel vaccines;
• Human medicine, with implications for cardiovascular disease, obesity and organ xenotransplantation, for all of which the pig stands as a superb stand-in for humans

Conventional genetic breeding that we've used for centuries and especially in the last 60 to 70 years has resulted in better growth rates, leaner carcasses and improved litter sizes.

Genomics can target all these and many more traits with increased accuracy in delivering improvements and doing so much earlier in the pig's life – ideally at, or very soon after, birth. It is even possible for genomics to target traits in the prenatal fetus in utero.

Genomics are most valuable for traits that have low heritability, traits that are expressed late in life after the animal is fully mature and in animals that have a long gestation length. With this background, the dairy industry, with the cow having a gestation length of nine months, has been one of the first in the animal world to benefit from genomics.

For the pig, pork quality has been one of the earlier targets for genomics. Although moderately to highly heritable, the pork quality traits we want to measure are in the carcass, when the animal is dead and hence lost as a breeder by the time we get to measure its carcass quality. With genomics, these pork quality traits can be identified in animals soon after birth and animals with the best genomics characteristics can be preserved for breeding.

Genomics provide an estimate of the contribution of all the genes across the pig's genome. Now that the entire pig genome has been sequenced, a DNA strip containing 60,000 SNPs (single nucleotide polymorphism) has been developed and can be used to test candidates for suitable traits. This SNP chip has greatly accelerated the targeting of desired traits.

Several aspects of pig genomics were covered by Don Stoneman in an article in the April 2013 issue of Better Pork. The high-tech chip may halt the scourge of PRRS, so the area I shall concentrate on here is genomics as applied to identifying pigs with better genetic immunity to disease, most specifically PRRS virus (PRRSV).

In 2007, the PRRS Host Genetic Consortium (PHGC) was created to explore genetic improvement for PRRS control and enhanced response to vaccines and infectious disease challenges.

As of a year ago, the PHGC has conducted 13 PRRSV infection experiments using two strains of PRRSV (an old strain and a more recent, still circulating strain) on 2,600 commercial, three-week-old, high-health pigs from six genetic companies in the United States and Canada, all negative for PRRSV, Mycoplasma hyopneumoniae, swine influenza virus and porcine circovirus type 2. Measurements showed that viral load and weight gain were significantly heritable. Other traits like viremia, production of cytokines and antibody responses also showed moderate heritability.

All experimental pigs' DNAs were genotyped with the 60K SNP chip and analyzed.

Based on disease traits related to weight gain and viral load, pigs could be placed into one of four groupings: high virus load/low weight gain (HvLg); high virus load/high weight gain (HvHg); low virus load/high weight gain (LvHg); and low virus load/low weight gain (LvLg).

Pigs in the LvHg group fall in the category of "resistant" to PRRSV infection. HvLg pigs are sensitive to PRRSV infection. Pigs in the LvLg group fall into an ambivalent category that does not produce any significant advantage. Pigs in the HvHg group are in a subgroup that is probably "tolerant" to PRRSV infection – that is, they retain normal growth in presence of high PRRSV loads.

These pigs would logically be targeted as ones that have the genetic components for protection against PRRSV.

Overall, the PHGC project has already delivered several beneficial spinoffs, including a large number of samples suitable for development of new PRRS diagnostic tests or probing for alternative mechanisms of PRRSV control. Also of importance, the PHGC project has identified a line of SCID (severe combined immunodeficiency) pigs at Iowa State University. SCID is a rare human (and animal) disease depicted in the 1976 movie, Boy in the Plastic Bubble. These SCID pigs can now be used to further studies on this disease and other genetic diseases in humans and animals.

In short, sequencing of the pig genome and developments in genomics of the pig are leading us into a brave new world of identifying beneficial characteristics in pigs soon after birth. One of the earliest traits that genomics have been used for enhancement has been pork quality. Currently, the PRRS Host Genetic Consortium has identified pigs that are genetically tolerant to PRRSV infection, whereby they continue to grow normally in the presence of very high PRRSV loads, which points us along the path to pigs with the genetics that make them immune to PRRS disease. BP

S. Ernest Sanford, DVM, Dip. Path., Diplomate ACVP, is a swine specialist with Boehringer Ingelheim Vetmedica (Canada) in Burlington. Email: ernest.sanford@boehringer-ingelheim.com.