Running The Genetic Reverse

As demand goes, so goes opportunity in the beef business, says Ben Brophy, director of genomics commercialization for Cargill. Our focus is on tools to improve beef demand. Consequently, he explains the bottom-line efforts of Cargill's cattle-feeding and beef-processing enterprises they're among the nation's largest are to increase consumer acceptance of beef products by increasing the consistency

“As demand goes, so goes opportunity in the beef business,” says Ben Brophy, director of genomics commercialization for Cargill. “Our focus is on tools to improve beef demand.”

Consequently, he explains the bottom-line efforts of Cargill's cattle-feeding and beef-processing enterprises — they're among the nation's largest — are to increase consumer acceptance of beef products by increasing the consistency of products that consumers want.

To achieve this in an affordable manner, Brophy says, “It's all about getting the right cattle into the right management groups and fed to the right end point to optimize their value. It revolves around identifying what technology exists to make product improvement and to increase the accuracy of selection. We (the industry) must move away from producing commodity beef, because there's no money in it.”

That's what led Cargill to seriously consider DNA-based tools for cattle selection and management. In turn, this led to a collaboration with MMI Genomics (wholly owned subsidiary of Metamorphix, Inc.) and development of a new concept. The results could be the new frontier of genetic evaluation in the cattle business, especially when it comes to hard-to-measure, complex metabolic traits such as feedlot gain and carcass tenderness.

Cargill entered a joint development and marketing agreement with MMI Genomics five years ago. The goal was to determine if an animal's genotype could be known for specific trait areas and, if so, whether that information could be used to boost production efficiency and retail beef consumer acceptance.

The result is a unique genetic evaluation tool called “molecular genetic value” (MGV), a proprietary tool and estimate of an individual animal's genetic potential.

“Specific phenotypic traits are controlled by more than one genetic marker. The MGV calculates the effect that each DNA marker contributes to the result by assessing both the size of the effect (small or large) and the direction of the effect (positive or negative), and combining the information for all markers into a single value that can be utilized as an overall indicator of genetic potential,” explains Sue DeNise, vice president of genomics research at MMI.

So for the tests available, a unique MGV is calculated for each animal tested.

Starting with the genes

To get your brain wrapped around this notion, it helps to remember the genesis of estimating genetic merit of cattle. Ever since Gregor Mendel developed his pioneering theories on heredity with pea plants and mice, the most basic goal of livestock geneticists has been to accurately predict the phenotypic outcome — the actual performance of animals — based upon genetic merit contributed by the parents.

Modern genetic evaluation began with performance ratios, then Estimated Breeding Values based upon those ratios for within-herd selection. Next came Expected Progeny Differences (EPDs), which made it possible to compare animals within breed that were raised in diverse environments.

More recently, some breed organizations have focused on developing predictive measures that address more directly the trait in question rather than indicators of the trait. For instance, an EPD for yearling scrotal measurement serves as an indicator of heifer fertility; an EPD for heifer pregnancy, though requiring more data collection, gets at the trait directly. Some EPDs now also incorporate data about what genes an animal possesses.

Each step increases prediction accuracy, but all seek to identify genetic merit by looking backwards, measuring phenotype in order to estimate genetic potential. MGV turns that approach upside down.

According to DeNise, “MGVs are created from the actual genetic makeup of an individual animal, as measured by the genotypes for markers at each location. EPDs are estimated from phenotypes of animals that have a genetic relationship: offspring, progeny and collateral relatives. MGVs estimate from the cellular level (genes) forward to the end point, whereas EPDs use the endpoint to predict backwards to the gene.”

To carry the comparison a step further, MGVs mean you can identify genetic merit earlier in an animal's life — at any time from birth to death, and that the genetic merit will never change over an animal's lifetime. Since EPDs rely on an animal's own performance, and that of relatives — especially progeny, it takes years to build accuracy of prediction to levels of near certainty, and the value changes as more information is added.

With an MGV, they either have specific genes or they don't. Unlike EPDs, however, MGVs at least those used for sorting cattle can include additive and non-additive effects. Traditionally, science has said EPDs account for only additive effects.

Non-additive effects include gene interactions, such as gene dominance and epistasis. MMI is exploring the contribution of these to MGVs.

“EPDs are estimates based on the phenotype of relatives, primarily progeny, measuring what gets passed and the additive effect (what proportion of variation is passed on),” DeNise says.

Real-world genomic measures

“Not every marker accounts for the same amount of variation (genetic and subsequently phenotypic) and not all are positive for it. MGV is a single value expressing the net size of the effect,” explains Tom Holm, MMI manager of business development.

As such, Cargill and MMI say MGVs represent a significant amount of the genetic variation for specific trait areas.

Consider carcass marbling. According to DeNise, in a sample of commercial Angus cattle, MMI's marbling evaluation tool (Tru-Marbling) accounted for 25% of phenotypic variation and 70% of total genetic variation — the MGV is 36% heritable.

DeNise says potential users of DNA diagnostics need to ask suppliers how many markers their tests represent, the heritability, and how much genetic and phenotypic variation their test accounts for.

MMI identified 786,000 proprietary bovine single nucleotide polymorphisms (SNPs) in 2001. Think of these as genes and signposts to genes. DeNise says 115,000 SNPs have been identified in public research as of March 2006.

Of MMI's genome sequence, they identified and utilize a panel of 128 proprietary SNP markers in their Tru-Marbling test for seedstock (89 markers in their feedlot test). These markers are strongly associated to marbling score.

MMI's Tru-Tenderness test for Angus utilizes a panel of 11 DNA markers, which are strongly associated with meat tenderness as defined by Warner-Bratzler shear force. MMI is also near completion on a feedlot average daily gain diagnostic — Tru-Gain — that utilizes 92 proprietary SNP markers.

The tests have been validated in Angus cattle and crossbred feeders. In fact, 4,000 steers in Cargill feedlots — more than 20 million genotypes — were part of the first association study. This was followed by an expanded validation study that included 30,000 steers and heifers in eight feedlots.

Using marbling as an example, this means they now know a particular MGV equates to a specific range of phenotypic marbling scores. Brophy explains this means a feedlot can manage cattle to optimum genetic potential, such as not overfeeding cattle that don't have the genetic potential to grade Choice.

For Cargill's beef packing business, “Forecasting supplies from a quality-grade mix standpoint changes the dynamics of forward-selling beef product and conversation with the customer,” Brophy explains

The same holds true with data from the Tru-Gain test. “A certain percentage of cattle will never make money because they grow too slow,” Brophy says. This information enables them to cut their losses on such cattle.

“We're planning to use the technology as a sorting tool in our feedlot business. Think of the technologies that have already existed, then consider what markers and marker-assisted management add to it. It's all about getting the right management inputs into the right cattle and managing individuals rather than groups in order to optimize their value,” he says.

In the world of seedstock production, the benefits of DNA-based genetic evaluation means desired genetics can be identified and utilized sooner.

“It's an opportunity to decide early whether you want to place an animal in a performance test, or use that yearling bull or heifer,” Holm says. “It increases the accuracy of selection and decreases the time it takes to put improved genetics into use.”

In sum, DeNise explains, “MGVs can be used to rank animals based on their genetic potential to express the trait. These rankings can then be utilized in comparing one animal against any other, within or across breed, so decisions can be made on whether to keep, breed, flush, cull or sell specific animals.”

None of this suggests that MGVs, or the concept behind it, will replace EPDs. For one thing, it's easier and less expensive to use traditional scales of measurement, be it a scrotal tape for scrotal circumference or a scale for weaning and yearling weight. And DNA-based tests such as MGV come at a higher cost than producers are used to — Tru-Marbling costs $145 and Tru-Tenderness is $65.

Moreover, Holm is quick to point out, “There may be correlated traits associated with these markers that we don't know about, so the limiting factor is this information needs to go into the total package of selection. Value how important particular traits are in your operation and don't lose sight of what the net value of the genetic package means to you.”

Finally, as exciting as the technology is, Brophy says, “The only way for this technology to be successful is for us to create opportunities for beef producers to receive value from their ability to create it.”