purina-institute-genomics

DNA

Genomics

purina-institute-dna-section

The scientific world is expanding our knowledge of how biology works at the most minute levels. This requires an in-depth understanding of how DNA gets translated into cellular action. 

DNA contains the chemical codes that provide the instructions for every cell function. By tracking which genes are turned on or off under different conditions, researchers can identify how gene expression changes between healthy and unhealthy dogs and cats and then evaluate the impact of nutrients on gene activity.

Purina was one of the first pet food companies to apply omics to better understand the connections between nutrition and genetics. This molecular-level focus continually reveals new mechanisms by which nutrients can improve pet health.

Purina's research

purina research

In 1999, Purina partnered with Cornell University to develop the Canine Reference Family DNA Distribution Center, a common platform for worldwide genetic data exchange. This canine reference family DNA helped researchers place hundreds of markers near specific genes and chromosomes, improving studies of how diseases – such as familial cancers – develop in both dogs and people.1 Purina also supports DNA sequencing research, which contributed to the completion of the international, multi-institutional collaboration leading to the first whole canine genome sequence. With more accurate knowledge of the canine genome, scientists can better compare DNA among dogs and other species to understand how genetic changes can affect health.2,3 Purina's studies have shown, for example, how nutrition can influence gene expression in dogs with osteoarthritis.4,5

In 2004, for the first time the whole canine genome was sequenced with DNA from a Boxer.

purina research on cats

The first whole domestic feline reference genome sequence was published in 2007.6 Since then, Purina researchers collaborated with other scientists to create a higher resolution map of the feline chromosomes. This was then used to generate a more detailed scaffold for the existing DNA sequence of the feline genome.7 Working with other geneticists, Purina scientists also analyzed the genome sequences of three Purina pedigreed cats. These cats, with known generations of “relatives,” are a powerful resource for studying breed-specific diseases. When cats come from long lines of similar breeding, this can amplify the impact of genes that confer higher risk for disease such as polycystic kidney disease (PKD) in Persian cats. Studying the DNA of these cats provides opportunities to find such genes, assess their impact, and develop new ways to improve health care for all cats.8

DNA for the first complete feline genome sequence came from Cinnamon, an Abyssinian cat.

Osteoarthritis research in dogs

Purina also used omics expertise to study arthritis in dogs. Osteoarthritis afflicts 1 in 5 dogs.9 With every step, this painful condition slows down the lifestyles that pets share with their owners.

genomics

For a new solution to this old problem, Purina scientists analyzed the impact of diet on gene expression and discovered that omega-3 fatty acids can improve cartilage cell health.

When Purina researchers compared gene expression in the joint cartilage cells of healthy dogs with those of arthritic dogs, genes in the cells affected by arthritis showed upregulation of cartilage-degrading enzymes, called metalloproteases. Enzymes that inhibited degradation were downregulated. 3-4

Previous studies showed that omega-3 fatty acids can reduce inflammation, a trigger for the biochemical cascade that leads to joint cartilage breakdown.

In a 9-week clinical trial with 24 client-owned dogs already scheduled to undergo tibial plateau leveling osteotomy (TPLO) surgery for one stifle, dogs fed a diet supplemented with omega-3 fatty acids had lower plasma levels of inflammatory markers and the cartilage-degrading enzyme, MMP-9. In the non-surgical leg, they also showed increased synovial levels of eicosapentaenoic acid (EPA) and an inhibitory enzyme for the metalloproteases that degrade cartilage.5

In a separate study, force plate analysis showed that dogs with naturally occurring arthritis had improved mobility when fed a diet high in omega-3 from fish oil.10

Further studies have shown that feeding an omega-3 and protein-enriched diet can result in lower synovial fluid PGE2 (a pro-inflammatory factor) concentration and can reduce pro­gression of osteoarthritis in the 6 months following tibial plateau leveling osteotomy.11 In another study, when compared to dogs fed a maintenance (control) diet, the dogs fed an omega-3 and protein-enriched diet showed improved peak vertical force and vertical impulse - which are measures of weight bearing and gait analysis for lameness - following TPLO surgery.12

Key things to remember

  • Purina’s long history of collaboration with other scientists has helped advance genome mapping and DNA sequencing for dogs and cats.
  • The molecular-level focus of genomics helps reveal new mechanisms by which nutrients can influence gene expression to improve pet health.
  • Purina’s studies have shown how nutrition can help improve the joint health and mobility of dogs with arthritis.
  • Dogs fed a diet supplemented with omega-3 fatty acids had lower plasma levels of inflammatory markers and the cartilage-degrading enzyme, MMP-9.

Find out more

  1. Breen, M., Jouquand, S., Renier, C., Mellersh, C.S., Hitte, C., Holmes, N.G., & Galibert, F. (2001). Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes.Genome Research, 11(10), 1784–1795. doi: 10.1101/gr.189401
  2. Lindblad-Toh, K., Wade, C.M., Mikkelsen, T.S., Karlsson, E.K., Jaffe, D.B., Kamal, M., & Lander, E.S. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 438(7069), 803–819. doi:10.1038/nature04338
  3. Hannenhalli, S.S., Middleton, R.P., Levy, S., Perroud, B., Holzwarth, J.A., McDonald, K., & Hannah, S.S. (2006). Identification and cross-species comparison of canine osteoarthritic gene regulatory cis-elements. Osteoarthritis and Cartilage, 14(8), 830–838.
  4. Middleton, R.P., Hannah, S.S., Perroud, B.N., & McDonald, K.K. (2003). Gene expression profiling of osteoarthritis from canine chondrocytes. The development of a canine OA microarray chip. Poster session presented at the 49th meeting of the Orthopaedic Research Society, New Orleans, LA.
  5. Hansen, R.A., Harris, M.A., Pluhar, G.E., Motta, T., Brevard, S., Ogilivie, G.K., & Allen, K.G.D. (2008). Fish oil decreases matrix metalloproteinases in knee synovia of dogs with inflammatory joint disease. Journal of Nutrition, 19, 101–108. doi:10.1016/j.jnutbio.2007.01.008
  6. Pontius, J.U., Mullikin, J.C., Smith, D.R., Agencourt Sequencing Team, Lindblad-Toh, K., Gnerre, S., & O'Brien, S. J. (2007).  Initial sequence and comparative analysis of the cat genome. Genome Research, 17(11), 1675–1689.
  7. Li, G., Hillier, L.W., Grahn, R.A., Zimin, A.V., David, V.A., Menotti-Raymond, M., & Murphy, W.J. (2016).  A high-resolution SNP array-based linkage map anchors a new domestic cat draft genome assembly and provides detailed patterns of recombination.G3: Genes|Genomes|Genetics, 6(6), 1607–1616.
  8. Farias, F.H.G., Tomlinson, C., Labuda, J., Perez-Camargo, G., Middleton, R., & Warren, W.C. (2017). The practical use of genome sequencing data in the management of a feline colony pedigree. BMC Veterinary Research, 13, 225.
  9. Tirgari, M., & Vaughan, L. (1975). Arthritis of the canine stifle joint. Veterinary Record, 96(18), 394-399.
  10. Moreau, M., Troncy, E., del Castillo, J.R., Bédard, C., Gauvin, D., & Lussier, B. (2013).  Effects of feeding a high omega-3 fatty acids diet in dogs with naturally occurring osteoarthritis. Journal of Animal Physiology and Animal Nutrition, 97, 830–837.
  11. Verpaalen, V.D., Baltzer, W.I., Smith-Ostrin, S., Warnocki, J.J., Stang, B., & Ruaux, C.G. (2018).  Assessment of the effects of diet and physical rehabilitation on radiographic findings and markers of synovial inflammation in dogs following tibial plateau leveling osteotomy. Journal of the American Veterinary Association, 252(6), 701–709.
  12. Baltzer, W.I., Smith-Ostrin, S., Warnock, J.J., & Ruaux, C.G. (2018). Evaluation of the clinical effects of diet and physical rehabilitation in dogs following tibial plateau leveling osteotomy. Journal of the American Veterinary Association, 252(6), 686-700. doi: 10.2460/javma.252.6.686.