Genomics' potential to increase profit in the beef industry is enormous, but no one knows how far away it is. First in a two-part series.
Commercial applications of genomics technology are finally coming home to roost in the beef industry. In fact, the world's first commercial diagnostic DNA test for a production trait — the GeneSTAR™ marbling test — will be launched in the U.S. this June.
Yet, despite the flood of chatter and research dollars poured into unlocking the secrets of the bovine genome the past decade, beef producers have yet to see much benefit.
“What the industry has been waiting for are tests for production traits — traits that are difficult or expensive to measure in a conventional production system,” says Jay Hetzel, chief scientific officer for Texas-based GenomicFX and founder of Genetic Solutions, a company recently acquired by GenomicFX.
Consider marbling, for instance, a trait of economic performance that can be and is measured. In fact, a number of producers are currently selecting for or against marbling via expected progeny differences (EPDs), which predict marbling directly, or its close cousin, intramuscular (IM) fat percentage.
Currently, however, marbling is costly to measure. And, actually moving those results into the selection process is time consuming. So, if animals could be identified through their DNA as possessing genes that increase or decrease marbling, the thinking is that selection and genetic improvement would take a giant leap forward.
“Genomics will allow us to manage genetic improvement across many different traits at the same time,” explains Steve Kappes, national program leader for USDA's Agricultural Research Service (ARS) animal production germplasm unit.
“Traits that you know have a negative relationship with other traits are the ones where genomic tools (diagnostic tests, marker-assisted selection and the like) will have the greatest impact,” says Kappes. Genomics, he says, will allow producers to select for higher growth, for example, without dragging birth weight and dystocia problems along with it.
Bottom line, Hetzel says, “Genomic information can help with decisions made by any number of players in the beef production chain.”
Consequently, even though some producers are skeptical, many are also anxious to try the new technology. Hetzel says, “While producers may be growing impatient for the new technology, they need to realize this research started only about 15 years ago. The technical challenges are such that commercial applications could not be expected before now.”
The Long, Winding Helix
Genomics requires understanding the molecular material that determines heredity, Kappes explains. In other words, genomics is identifying the genes that exist in cattle and how they function on their own and in relation to other genes.
Ronnie Green, chairman of the emerging technologies committee for the Beef Improvement Federation, points out that genomics is also figuring out how to manage genes once they and their function have been identified.
For example, assume you've identified genes within an animal that you know impact tenderness. Over time, you need to use the same diagnostic tools to help manage the expression of the gene.
“We're closer to exploiting the potential of genomics than we have ever been before, but reaching out and grasping its full power means we still have lots of work left to do, things like sequencing the bovine genome,” says Kappes. He explains that sequencing the bovine genome — knowing which genes exist at which locations on which chromosomes — is fundamental to fully grasping the golden ring of promise and is still at least $20 million and a year or two away.
That's how much money ARS estimates sequencing about 70% of the bovine genome will cost. Barring extraordinary circumstances, Kappes explains the 2003 budget is the earliest the industry could hope for the dollars needed to sequence the cattle genome.
However, extraordinary circumstances may in fact prevail. Researchers rocked the world earlier this year when they announced that they had sequenced the human genome — about 94% of it accounting for 30,000-40,000 protein-coding genes; far fewer than anticipated.
According to Roger Wyse, managing director of Burrill and Co., the opportunity to understand more about the recently sequenced human genome, via comparative genomics — using the gene map in one species to identify the genes in another — may stimulate funding for the bovine genome quicker. As well, he points out concerns about animal diseases such as BSE and foot-and-mouth are fueling interest from the human side to come up with the dollars to find out more about the beef genome. Wyse is also coordinator of the Livestock Genomics Initiative, which is gaining private industry support to lobby for accelerated public funding.
Kappes explains that while a bovine gene map would help human researchers carry their work further, “We in the beef industry can leverage the research dollars spent on the human side so the cost of beef genomics research is not as high as it was 10 years ago.”
But, sequencing the genome is only the starting place. In the case of the human genome, for instance, Wyse says having the sequence is like knowing all the numbers in a phone directory. What's left is finding out to whom those phone numbers belong, what they do for a living and how all those people exist and interact as a society. It's a task some believe will take more than 20 years.
Taking Advantage Today
But, you don't have to know all that information to locate one gene within the genome that can impact your business in a major way.
Companies are already developing commercial applications that could help producers long before the bovine genome is sequenced. In the case of GenomicFX, they're introducing the GeneSTAR marbling test to the U.S. this summer. It's been available in Australia for about a year.
“We think the technology has great promise,” says Paul Genho, vice president and general manager of the King Ranch in Texas. “We're already incorporating GeneSTAR tests into our bull selection.”
By using a blood or hair sample from an animal, GeneSTAR detects low and high marbling forms of the thyroglobulin gene, which impacts marbling. It is likely an example of the type of DNA diagnostic tests producers will begin seeing more of. And, Hetzel says it serves as a sturdy example of both the strengths and weaknesses encountered with tests like these.
On the plus side, Hetzel explains, “It's a test for a trait with high economic value to the industry. It's a particularly valuable test because it can be used without knowing the animal's pedigree. And, the result is quite simple.”
Basically, the GeneSTAR test tells a producer whether the animal being evaluated has one copy, two copies or no copies of the high marbling form of the thyroglobulin gene. Since the mode of inheritance is recessive — just like red is to black in coat color — an animal needs two copies of the gene to have an opportunity to fully express the trait.
“It's only one of the genes associated with marbling, so it's only part of the total marbling story in terms of genetics, and that will remain the case until the other genes for marbling are identified,” says Hetzel. That will be a weakness of any test for any gene until all the genes that impact a trait are known, he adds.
On the upside, however, the gene identified by GeneSTAR accounts for about 10% of the genetic variation in marbling — considered a large effect by researchers. And, it tests for the gene itself rather than a marker gene believed to be linked to the gene in question.
Hetzel says the test works consistently across different breed populations, something that will likely not be the case with other genes that are uncovered for this and other traits. All in all, the test offers producers the opportunity to identify high marbling seedstock with less progeny testing and more efficient testing of the progeny that are evaluated.
So, this test or future tests like it cannot guarantee the phenotypic expression of a desired trait — marbling in this case — any more than an EPD can. But, it does allow producers to select and manage with a higher degree of accuracy.
“Having this genetic information adds accuracy to the genetic evaluation of an animal sooner, that's all,” explains Green, who is also director of genetic operations for Future Beef Operations, LLC. Unfortunately, he adds, “What some people want to make it into is a situation where they only need the DNA information and none of the other genetic information. That's not how it works.
“People always think of traits like color and polledness when they think of DNA, so they think DNA tests for these other traits can tell them whether an animal has this trait or that trait. But, it's only going to tell you whether you have a little more of this trait or a little less of that one,” Green says.
Kappes believes producers will be living with EPDs until the day the genes are identified that explain at least 95% of the genetic variation between animals.
Hetzel predicts based on research that has already been done, the beef industry can expect diagnostics for carcass traits like marbling in the next few years, traits like growth and tenderness in the medium term, traits like disease resistance and feed efficiency in the medium to long term and traits like reproduction in the long term.
“For any trait that's easy to identify and select for now, it will be easy to identify the QTLs (the location on the chromosome that contains a gene or genes affecting economically important quantitative traits). For any trait that's difficult to identify and select for, it will be more difficult to identify the QTL,” says Kappes.
“We believe the GeneSTAR marbling test is only the first installment in a series of new DNA tests and genomics tools for the beef industry,” says Hetzel. “The future is bright.”
A Genomics Glossary
Allele (alielle) — Any of several alternative forms of a gene. A baby inherits genes for eye color from both parents, as an example, but the allele for that gene might be blue from the mother and brown from the father.
Base — On the DNA molecule, which is comprised of smaller molecules called nucleotides, a base is one of the four chemical units that, according to order and pairing, represent the different amino acids, which are the building blocks of proteins. The four bases are adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, uracil (U) substitutes for thymine (T).
Base Pair — Two nucleotide bases on different strands of the nucleic acid molecule that bond together. The bases can pair in only one way: adenine (A) with thymine (T) in DNA, or adenine (A) with uracil (U) in RNA and guanine (G) with cytosine (C).
Cell — The smallest structural unit of living organisms that is able to grow and reproduce independently.
Chromosomes — Threadlike components in the cell that contain DNA and proteins. Genes are carried on chromosomes. Cattle contain 30 pairs of chromosomes.
Cytoplasm — Cellular material that is within the cell membrane and surrounds the nucleus.
DNA (Deoxyribonucelic Acid) — The molecule that carries the genetic information for most living systems. The DNA molecule consists of four bases (adenine, cytosine, guanine and thymine) and a sugar-phosphate backbone, arranged in two connected strands to form a double helix.
DNA Fingerprinting — The use of restriction enzymes to measure the genetic variation of individuals. This technology is often used as a forensic tool to detect similarities in blood and tissue samples at crime scenes. In the cattle business, this technology is used to verify the parentage of individual animals.
DNA Sequence — The order of nucleotide bases in the DNA molecule, which provides the information an organism needs to develop and function.
Double Helix — A term often used to describe the configuration of the DNA molecule. The helix consists of two spiraling strands of nucleotides (a sugar, phosphate and base) joined crosswise (like rungs on a ladder) by specific pairing of the bases.
Enzyme — A protein catalyst that facilitates specific chemical or metabolic reactions necessary for cell growth and reproduction.
Eukaryote — A cell or organism containing a true nucleus, with a well-defined membrane surrounding the nucleus. All organisms except bacteria, viruses and blue-green algae are eukaryotic.
Gametes — Cells (sperm and egg) that carry the material and information for heredity from one generation to the next.
Gene — A segment of chromosome. Some genes direct synthesis of proteins, while others have regulatory functions. A gene is a stretch of DNA in which the arrangement of nucleotides creates a sort of code, which in turn describes a particular type of protein. Cells use these descriptions to manufacture the described protein that directs what the cell is to do or is to become.
Gene Mapping — Determination of the relative locations of genes on a chromosome.
Gene Sequencing — Determination of the sequence of nucleotide bases in a strand of DNA.
Genetic Code — The mechanism by which genetic information is stored in living organisms. The code uses sets of three nucleotide bases (codons) to make the amino acids, which in turn constitute proteins.
Genome — The total hereditary material of a cell, comprising the entire chromosomal set found in each nucleus of a given species.
Genomics — The study of genes and their function.
Genotype — The genetic makeup of an individual or group.
Heredity — Transfer of genetic information from parents to progeny.
Homologous Pair — A pair of chromosomes an organism inherits that contains information for the same type of traits; one chromosome in the pair is inherited from the mother and the other from the father. Each chromosome in the pair contains the same kind of genes, but not necessarily the same version (allele).
Locus — A position in the DNA sequence, relative to others. This can describe a specific polymorphic site or a large region of DNA sequence in which one or more genes might be located.
Marker (For A Gene) — A section of DNA that is polymorphic (see polymorphism), which can be used to identify whether or not nearby linked genes are present.
Molecular Genetics — Study of how genes function to control cellular activities.
Nucleic Acids — Large molecules, generally found in the cell's nucleus and/or cytoplasm that are comprised of nucleotide bases. The two types of nucleic acid are DNA and RNA.
Nucleotides — The building blocks of nucleic acids. Each is composed of sugar, phosphate and one of four nitrogen bases. The sequence of the bases in the nucleic acid determines which proteins are made.
Nucleus — The structure within eukaryotic cells that contains chromosomal DNA.
Phenotype — Observable characteristics resulting from interaction between an organism's genetic makeup and the environment.
Protein — A molecule composed of amino acids. There are many types of proteins, all carrying out a number of different functions essential for cell growth.
Polymorphism — A stretch of DNA located at the same relative location on a chromosome but differing in the amount or order of nucleotides.
QTL (Quantitative Trait Loci) — In cattle, the location on the chromosome that contains a gene or genes affecting economically important quantitative traits such as tenderness.
Recombinant DNA (RDNA) — The DNA formed by combining segments of DNA from different types of organisms.
Recombination — The natural exchange of alleles at two heterozygous loci as homologous chromosomes divide into two groups during the process in which they become gametes.
RNA (Ribonucleic Acid) — A molecule similar to DNA that functions primarily to decode trace amounts of substances. Such tests are useful in biomedical research to study how drugs interact with their receptors.
Ribosome — A cellular component containing protein and RNA which is involved in protein synthesis.
Sequencing — Decoding a strand of DNA or gene into the specific order of its nucleotides: adenine (A), cytosine (C), guanine (G) and thymine (T). This analysis can be done manually or with automated equipment. Sequencing a gene can require analyzing an average of 40,000 nucleotides.
Transgenic Organism — An organism formed by inserting foreign genetic material into the germ line cells of organisms.
Source: Adapted with permission from a glossary of terms provided by the Biotechnology Industry Organization (BIO).
Words Of Caution
As with any new technology, Ronnie Green, chairman of the emerging technologies committee for the Beef Improvement Federation, says producers and technology firms must exercise caution.
Through simple chance and association, Green explains it's quite possible that if you test enough gene markers against enough traits that you can find a relationship, when in fact no real relationship exists.
“If I were a producer,” Green says, “I would only buy a test if the company selling it knows which gene they're testing for, which protein that gene produces, and I'd want a substantial amount of genotyping to go with it. If it's a test for a gene marker, they'd better have a substantial amount of information proving the relationship between the marker and the trait in question. Most of these things we are working with today are a fair distance from that criteria.”
Jay Hetzel of GenomicFX adds, “Our approach is that we won't market a product until we have the supporting information. Product assurance is a key area for us. We only recommend use of products with extensive information that verifies the results.”
In the case of GeneSTAR, this information includes everything from the frequency of the allele within the population, to knowing the effect of the gene on IM fat across different breed populations, to understanding the mode of its inheritance.
“This is an infant field that is untested, and we have to hope that everyone who is involved with this will do their homework before they make promises,” says Green.
How To Decode Genomes
If the prospect of dealing with genomics has you questioning your scholarly capabilities, the good news is that no one has to understand the magic of all of the science to take advantage of the benefit it offers.
Ronnie Green, chair of the emerging technologies committee for the Beef Improvement Federation, likens it to taking advantage of a fax machine. It isn't necessary that you understand how written word is transmitted over the same line that carries your voice.
“Sometimes, you just have to believe something will work, prove to yourself it works, then use the technology,” says Green. In the case of genomics, he believes producers will reap benefits by beginning to understand the basics.
Green says, “Producers need to understand what DNA is and what genes do. They need to understand there is a difference between a gene and a marker for a gene, that when you're talking about a marker, no matter how tightly associated with the gene, you can come up with a substantial amount of selection error.”
Humans have 23 pairs of chromosomes (cattle have 30) that exist within the nucleus of a single cell. Each of these chromosomes is filled to the brim 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 combination and arrangement of nucleotides creates a code, which describes a particular type of protein. These proteins, in turn, tell the cells what they will do and what they will become.
Now, remember those chromosomes? For each of the 30 pairs, one half is inherited from each parent. If you know which genes — more importantly which specific version of each gene (allele) — occur on which chromosome, where and how frequently, you can use the power of heredity to transmit the genes you want more of the time.
Take, for example, coat color. We know that a black Limousin bull can carry both an allele for red color and one for black. We know black is dominant and red is recessive, and our Limousin calf can only be red if it inherits an allele for red color from both the dam and sire.
Since black is dominant, we know that heterozygotes — those carrying only one allele for black — will be just as black as homozygotes — those carrying both alleles for color. Obviously, that doesn't make much difference to us once the calf is on the ground, but if we knew where the genes for red and black existed on the chromosome — and 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 expression of quantitative traits like tenderness and feed efficiency, which depend upon the interaction of multiple genes, are tougher nuts to crack. The concept, however, is the same.
That's why interest is blooming within the beef industry to sequence — identify all of the genes and where they exist — the bovine genome. Once the genes are identified, researchers can start unraveling what they do and how they interact with other genes.