“At some point there won't be any reason to buy or mate cattle without knowing the DNA in an animal, and the interaction between that DNA and the specific environment and management that will impact it,” says Calvin Gunter, director of corporate development for Bovigen, LLC, a genomics company.

That's the promise of DNA-based diagnostic tools, especially when it comes to the economically important traits toughest to measure, such as fertility, disease resistance and feed efficiency. In fact, this promise and more is behind the recently completed, $53-million Bovine Genome Sequencing Project (BGSP) begun three years ago. Sequencing is determining the exact order of the nucleotide base pairs in a strand of DNA (see “Basic Genomics,” p. 19).

The notion behind the international collaborative BGSP is to provide a publicly accessible foundation of information by which DNA-based tools and understanding can be developed to help the cattle industry achieve more efficiency through increased performance, decreased morbidity and mortality, a better understanding of how to transmit favorable genes, and more.

Via the quickly blooming field of comparative genomics, completion of the bovine genome sequence also provides human genome researchers more insight into that sequence, which was completed in 2003.

However, the pace toward fulfilling DNA-based promise in the cattle industry has disappointed more than one beef producer. Sure, you can use DNA to identify which calves were sired by which bull in a multiple-sire pasture. You also can measure which specific alleles an animal possesses for color and polledness. More recently, you can even begin to get a handle on some of the genes that contribute to carcass tenderness and Quality Grade.

While each of these can serve up substantial value, many producers are anxious for tests describing the input side of the equation, such as cycling early, breeding efficiently, successfully calving and breeding back. What about data indicating how efficiently one animal converts feed to gain compared to another? What about DNA related to actual profitability?

Chances are, by the time you read this, the first tests for some of these trait areas will have been introduced.

Welcome to the evolution

Fact is, technology is finally catching up with the promise of DNA diagnostics.

“What has occurred is enabling technology,” says Stewart Bauck, executive director of strategic development for Igenity®, the Merial-owned DNA diagnostics organization. Without wading too far into genomics' intellectual waters, which gets scary fast, Bauck explains the crux: Researchers and scientists have developed tools and infrastructure that enable them to obtain more DNA-based information faster and cheaper than before, while increasing accuracy.

Among these, he cites the advanced use of single nucleotide polymorphisms (SNPs — pronounced “snips”) for genotyping. In simplest terms, a SNP is a variation in the sequence of a single base pair of nucleotides at a particular gene or location within the gene. Knowing that a particular gene or particular DNA sequence exists at a specific location in an animal's genome is the basis of DNA-diagnostic tests.

“Much of the genetic variation is encoded in SNPs. We can measure them as if they're a single pair of genes; it's an easier and cheaper way to measure,” Bauck says. “Three or four years ago, a single SNP test cost $60-$70. Today, you can get results from Igenity for 8-10 traits for $35. It's rapidly entering the realm where everyone can use it.”

Of course, history also is catching up with the technology. As Gunter points out, there's more value to DNA-based knowledge than in the past, and likely more to come. Using parentage as an example, he explains, “Knowing the parentage of the animal didn't have as much value a few years ago as it does today. In the last 10 years, the value equation for knowing parentage has increased with the use of individual animal ID and the widespread availability of marketing alliances.”

Those first DNA-based parentage tests were introduced by a company since acquired by MMI Genomics, Inc. Tom Holm, MMI manager of business development, explains, “Producers' initial interest in the technology was driven by a desire to manage cattle in multi-sire breeding programs, yet be able to correctly ascertain individual sire identity and progeny parentage for the benefit of accurate genetic evaluations.”

Holm says subsequent uptake of trait-specific, DNA-based diagnostic tests has been driven by two primary factors: to increase the speed and accuracy of selection decisions for economically important traits, and develop selection tools for traits such as tenderness, which are difficult to measure using routine genetic evaluation techniques. Producers also discovered they could increase the market value of their genetics with DNA-based testing results.

USDA's recent acceptance of instrument-grading for quality and yield, and the development of similar instruments to objectively measure tenderness, likely point to increased value for the ability to identify and manage these traits more specifically.

Peeking inside the genes

In fact, all three of these companies offer a DNA diagnostic test aimed at sorting cattle based on the likelihood they possess genes for a tough carcass or a tender one. You'll find more specifics in Table 1. Suffice it to say, sorting through them has as much to do with understanding the philosophies of each company as their pricing and customer service.

At MMI, for instance, Sue DeNise, vice president of genomics research, explains the company employed what's termed “a whole-genome discovery process by which both DNA markers and their interaction with one another are documented.” When MMI's sequencing was done in 2001, the result was 700,000 SNPs gleaned from Angus, Limousin, Brahman and some Simmental. For perspective, the BGSP has so far captured about 115,000 SNPs from a line-bred Hereford animal.

That doesn't mean one sequencing project is necessarily better than the other; it just underscores the starkly different approaches organizations can take toward the same goal, be they public or private.

DeNise emphasizes MMI focuses on mapping as much genetic variation as possible. It also strives to tie its findings to phenotypic data. All told, via a business collaboration with Cargill Meat Solutions, MMI has evaluated 6,000 different markers in 4,000 animals and is validating the results in 25,000 head of fed cattle.

The culmination of all this work is something MMI terms a “molecular genetic value” (MGV), which may represent the next frontier of genetic selection (see next month's BEEF for more details). Holm explains, “The MGV incorporates both the size and the direction (positive or negative) of the genotype for each marker. MGVs are reported in the same units as the trait measurement (pounds of shear force, marbling score, etc.).”

DeNise says MGVs can be used to rank animals for their genetic potential at any age with the same accuracy of prediction. And because the MGV is comprised of dozens of markers, mating plans can be developed to maximize the probability of producing progeny with the highest genetic potential possible.

Using marbling as an example, the MMI test accounts for 128 markers. Rather than assign a value to each marker, producers receive a composite value — the MGV — representing the animal's total genetic value for all the markers.

Bovigen provides users of their marbling and tenderness tests with what it calls a “genetic progeny difference” (GPD). It's a numeric value associated with a DNA value for a specific trait, relative to the phenotypic expression accounted for by the DNA.

Somewhat akin to Expected Progeny Difference (EPD) indices, the notion is producers can select based on a value encompassing the three markers and two genes in their tenderness test, for instance, while also seeing the value for each marker contributing to the total.

“As the number of markers increases, the GPD will become far easier to use than keeping track of the number of stars for each marker,” Gunter explains. “The stars will still be important though, because each marker has a different level of effect on tenderness.”

The “stars” refers to Bovigen's genotype reporting: one star denotes an animal possessing one of two possible favorable alleles for the trait; two mean both alleles are favorable.

As for Igenity, it's launched a DNA-profiling product validated on 50,000 head that leverages the convergence of technologies.

“Before, everyone looked at two basic genomic buckets — parentage and diagnostics. With the Igenity profile, we can begin to merge them so, as we confirm parentage, we can also provide information that contributes to an animal's EPD as well as the EPD of its parents. It gives us insight into two generations at the same time,” Bauck explains. “The profile is a panel of tests that tells us about the genetic variation of an animal, its ability to transmit the genes, and the impact of those genes on individual animal production (performance and ability to transmit to progeny). Both favorable and unfavorable, I might add.”

More specifically, with a single sample, producers receive an Igenity profile that parent-verifies the animal to a sire, and includes genetic analyses for tenderness and other carcass traits such as carcass weight and lean yield, as well as confirmation of homozygous black or red carrier genotype. Simultaneously, producers can also choose to have their animals tested for persistent infection with bovine viral diarrhea.

When all is said and done, using a scoring system based on genotypic results, along with phenotypic performance data provided by producers, Igenity provides in-herd EPDs, scores and genetic evaluation for each profile.

“When used with other tools available in quantitative genetics, it gives us a better estimate of the worth of an animal, at a much earlier age,” Bauck says.

So, how do you choose tests and the companies offering them? Visit with them; ask them to tell you specifically what their diagnostics test for. Ask for validation. You can find reviews of tests submitted for third-party validation to the National Beef Cattle Genetic Evaluation Consortium at www.ansci.cornell.edu/nbcec.

For that matter, just getting reacquainted with the first geneticist, Gregor Mendel, and basic genomics is a great first step. As Holm notes, “People still refer to a marbling gene or a tenderness gene. Many still don't understand that hundreds of genes affect each trait.”

All these companies agree the potential of genomics is just starting to be realized.

“In a practical-minded industry like ours, there's been some disappointment at the speed of progress,” Gunter says. “But the rate of progress has been dramatic in terms of the production/development life cycle of other tools, such as pharmaceutical products, where the cycle can run 15-20 years. We're only 8-10 years into that cycle.”

Basic Genomics

You have a chromosome — actually you have 23 pairs of chromosomes while cattle have 30 pairs — that exist within the nucleus of a single cell. Each chromosome is filled with DNA — long, thread-like structures comprised of smaller molecules made up of nucleotides. These nucleotides are comprised of a sugar and phosphate molecule, along with one of four bases: adenine (A), thymine (T), cytosine (C) or guanine (G).

Next, along stretches of DNA, you find genes — 30,000-40,000 of them in humans — where the particular combination and arrangement of nucleotides creates a sort of code that describes a particular type of protein. These proteins, in turn, tell the cells what they will do and what they will become.

For each pair of chromosomes inherited, half from your mom, the other from your dad. Thus, if you know which genes — or more importantly, which specific version of each gene (allele) — occur on which chromosome, where and how frequently in the population, you can use heredity to transmit the genes you want more of the time.

Consider the simple mode of inheritance for coat color. A black Limousin bull, for instance, can carry both an allele for red and one for black. Black is dominant and red is recessive, so a Limousin calf can be red only if it inherits an allele for red from both its dam and sire. Since black is dominant, we know heterozygotes — those carrying only one allele for black — will be just as black as homozygotes, which carry both alleles for black color.

Obviously, that doesn't make much difference to us once the calf is on the ground, but if we knew the locations on the chromosome of the genes for red and black — like we do now — and could test our black bull for the existence of those genes, we would know before we ever bred him whether he was homozygous or heterozygous for the trait.

In turn, we can use that information to more effectively select for one expression of the trait or the other. It works the same way with horns and polledness, with horns being the recessive gene.

Certainly, the expressions of quantitative traits like tenderness and feed efficiency, which depend upon the interaction of multiple genes, are tougher nuts to crack, but the concept is the same.

Table 1. DNA Diagnostic Products*
Bovigen, LLC (www.bovigen.com)
Test What it measures Sample used How reported Cost Turnaround
GeneSTAR® Tenderness Markers related to calpain and calpastatin genes Blood, hair follicle or semen Marker genotype/genetic progeny difference $30-$45 1 week
GeneSTAR® Quality Grade Markers related to thyroglobulin gene Blood, hair follicle or semen Marker genotype/genetic progeny difference $30-$45 1 week
GeneSTAR® Black Genotype of black coat color Blood, hair follicle or semen Homozygous or heterozygous black and presence of confounding allele $30-$32 1 week
GeneSTAR® SireTRACE Parentage and ID Blood, hair follicle or semen Excluded or verified $20-$25 1 week
Igenity (www.igenity.com)
Test What it measures Sample used How reported Cost Turnaround
Igenity Profile includes: Tissue, blood or hair follicle (see below) $35 (tissue)
$40 (other)
7-10 days
Carcass Traits Markers related to back fat, ribeye area, hot carcass weight Score of 1-10
Coat Color Genotype of black or red coat color Homozygous or heterozygous black or red, and presence of confounding allele
Maternal Milk Yield Markers related to milk production Score of 1-10
Multi-Sire Parentage Parentage ID in multi-sire pastures Excluded or verified
Quality Grade Markers related to marbling Score of 1-10
Tenderness Markers related to calpain and calpastatin genes Score of 1-10
Yield Grade Markers related to Lean fat yield Score of 1-10
BVD-PI Testing Tissue or blood Positive or negative $2.50 with Ingenity profile 7-10 days
Commercial Ranch Genetic Evaluation Within-herd EPDs for traits of choice EPDs based on progency performance $35/bull/trait + Igenity profile for progeny 7-10 days
Horned-Polled (breed-specific) Horned, polled or scurred Horned, polled or scurred Varies 7-10 days
MMI Genomics, Inc. (www.mmigenomics.com) or (www.breedtru.com)
Test What it measures Sample used How reported Cost Turnaround
Tru-Parentage Parentage and ID Micro-Card blood spot Excluded or verified $16-$25 2-10 days
Tru-Polled Genotype of polled gene Micro-Card blood spot Homozygous or heterozygous polled $110 15 days
Tru-CoatColor (black) Genotype of black coat color Micro-Card blood spot Homozygous or heterozygous black $32 15 days
Tru-Myostatin Genotype of myostatin gene Micro-Card blood spot Copy number of myostatin gene $15-$25 monthly
*Based on company product offerings as of 02-01-07, from companies offering DNA diagnostics beyond parentage and products based on private and public research.