Turn on the right genes

A few years ago, Hill's Pet Nutrition introduced Prescription Diet Canine JD for dogs with arthritis and joint problems. The diet contains a specific omega-3 fatty acid that has been shown to "turn off" a degenerative enzyme that causes cartilage degradation. As a result, many dogs on the diet show improved range of motion, helping them to run and walk better.

Nothing exists yet in the dairy industry, but it's just a matter of time before commercial applications appear that link a cow's ration with gene expression. Some companies are already working on it.   

Eventually, nutrigenomics will revolutionize the way we feed cows. 

Nutritionists will be able to make better recommendations if they know how a cow responds to a particular diet at the molecular level, says Randy Baldwin, research animal scientist with the bovine functional genomics lab of the USDA Agricultural Research Service.

Targeted rations

That sounds fine in theory. But why get excited about something that could still be years away?

Perhaps to best answer that question, consider what's going on with chromium propionate.

In 2003, WashingtonStateUniversity researchers, working in partnership with Kemin Industries, found that chromium propionate improved feed intake and milk production when fed to cows during the transition period (21 days prepartum to 25 days postpartum). They concluded that chromium had a positive impact on fat metabolism. Then, a few years later, they looked specifically at the fat tissue of cows to see what was going on at the molecular level. Using DNA-microarray analysis — a core technology of nutrigenomics — the researchers found that chromium propionate supplementation up-regulated (turned on) approximately 400 genes and down-regulated (turned off) approximately 1,100 genes in the adipose (fat) tissue of dairy cows.

This up-regulation and down-regulation of genes could be one of the reasons why chromium propionate improves milk production and feed intake, says John McNamara, dairy scientist at WashingtonStateUniversity. Further research is planned, but "at this stage of the game, that is one of the reasons we think it works," he adds.

Although approved for use in swine, chromium propionate has not yet been approved by the U.S. Food and Drug Administration for use in cattle.

If chromium propionate is approved for use, it could be the first "nutrigenomic" application for dairy cows. Yet, there are many other potential applications.

One item of interest is butyrate, a volatile fatty acid produced in the rumen. In a developing animal, butyrate appears to be a messenger that tells the rumen to develop and take on mature characteristics, says the USDA's Randy Baldwin. In a mature animal, butyrate may play a role in maintaining or influencing the amount of rumen epithelium, he adds. Higher amounts of butyrate may, in fact, turn on the genes that help the rumen prepare for the next lactation.

Knowing how to influence these genes (through butyrate) could be very important, Baldwin points out. Rather than feeding cows a steam-up ration for three weeks prior to calving, a simpler and quicker way may be found.

"By gaining a better understanding of the nutrient/gene interactions, we're able to understand and even target dietary ration formulations to take advantage of beneficial responses," Baldwin says.

Other examples

In Australia, scientists are trying to identify which genes in beef cows are affected as the result of unfavorable feeding regimes or diets that are low in energy and protein. The idea is to find the genes that need to be regulated under different management strategies so cows can produce reasonably good meat even under unfavorable conditions, says Antonio Reverter, principal research scientist for CSIRO Livestock Industries in Queensland, Australia.

Others are interested in selenium. Many of the key enzymes associated with glycolysis (the breakdown of carbohydrates in a cow's body) are up-regulated or "turned on" by selenium. If selenium helps regulate the genes of these enzymes, then different formulations may be able to optimize carbohydrate metabolism, thus producing more energy and more milk.

Over time, scientists will be able to assess the effects of a ration change much more precisely — not only from an observational standpoint (better health, more milk produced), but also the effects at the cellular or molecular level. This, in turn, will help them predict what the animal will do under different feeding situations. It will make nutrition a much more quantitative science.

"These tools will be extremely powerful for people to look at the nutrients they are using in their diets," says Karl Dawson, research director at Alltech in Lexington, Ky.   

How the test works

The analogy of turning genes off or on, like a bank of lights, is fairly accurate.  Consider how the nutrigenomics test works:

  • Scientists extract ribonucleic acid (RNA) from the tissues of a cow. Why RNA and not DNA? DNA is constant throughout the body, day in and day out, regardless of external conditions. RNA, on the other hand, varies in different parts of the body, depending on external conditions. Therefore, it better reflects changes in the diet and targets those changes to certain body functions.
  • RNA, in fluid form, is applied to a computer chip, also known as a DNA microarray. This collection of microscopic DNA spots, dotted on a solid surface, can represent all of the genes in a cow's body.
  • It's also important to note that a special dye is added to the RNA.
  • Once the RNA is applied, a laser will cause some portions of the chip to fluoresce. Those are the areas where messenger RNA has paired up with a particular spot of DNA (see graphic). The dye that has been added to the RNA causes the new genetic base-pair to fluoresce.
  • The chip is scanned by a digital imager, giving scientists a chance to view the fluorescence and furthermore to identify the genes affected. (Each gene has its own specific location or "address" on the chip.)
  • A comparison is made between the new image — reflecting a change in the diet — and an old image before the dietary change was made. If a gene starts to fluoresce in light of a dietary change, it is "turned on." If it goes dark, it is "turned off."  In some cases, it may be beneficial to have a gene turned on; in others, it may be beneficial to have it turned off.
  • Some chips contain more than 30,000 genes, representing the entire genetic makeup or genome of a cow. But more specialized "focus chips" may capture 200 genes or so that have the most direct impact on carbohydrate metabolism or other body functions.





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