Finding them is the first step toward managing the problem
– By JAIME PULLMAN –
In March of this year, scientists from the Agricultural Research Service US Meat Animal Research Center (ARS USMARC) in Clay Center, Nebraska, gave the beef industry an online resource that we can all benefit from—even though you’ll probably never use it yourself. The scientists have created an online genomic resource that enhances the ability of animal researchers—and as a result beef producers—to get a whole new look at genetic potential.
As DNA testing becomes more commonly used as a part of breeding decisions, researchers are trying to ensure accuracy and make the most out of what can be determined from the results. The online resource is the culmination of more than two years of steady work during the 1990s, though some of the work began earlier.
Led by USMARC microbiologist Michael Heaton, PhD, the online genome includes 96 bulls representing 19 different breeds.
“The challenge was to find as many unrelated bulls as possible within a breed,” says Heaton, “and then acquire 100 straws of semen from each. This amount of material would provide enough DNA for the research we had in mind, and still have DNA to share with other researchers and DNA testing companies.”
The number 96 was also important because it fits the hardware format of the automated genotyping and sequencing technology platforms that Heaton used. They wanted to use as many different breeds as possible within the 96-bull collection in order to best represent the breadth of genetics in the nation’s beef population.
“We eventually settled on 19 beef breeds with four to six bulls per breed, based on the number of registered progeny,” Heaton goes on to explain. “The trick was to exhaustively search available pedigrees to find the bulls with the fewest shared ancestors. Many of our bulls had no shared ancestors in a five-generation pedigree. This helped ensure that we would be evaluating the widest possible cross section of beef genetics available, not just the most popular. Now when we analyze the genome sequence of these diverse bulls, we see a great variety of gene variants in U.S. beef cattle.”
According to ARS, the breeds represented in the panel are a fair representation of the US beef genetics pool from the year 2000. With the genetic information gathered and the technology available today, the online genome allows users to dramatically reduce the time and virtually eliminate the cost required to complete DNA analysis.
“My ultimate goal was to eliminate the slow and expensive piecemeal approach of DNA sequencing that we were doing previously, and instead, do it all up front,” continues Heaton. “Once the project was completed, we could focus on analyzing genes and finding those that cause disease, instead of simply just determining their sequences. Previously we would spend three months and $3000 sequencing and analyzing an important gene. Now we can analyze a gene online in an afternoon for free. This has greatly increased the rate at which we can find candidate mutations that may affect a gene’s function.”
The information was put together and made available to the public online, though it wasn’t intended for use directly by beef producers. Rather, it is intended for the researchers that examine the gene variants that impact beef cattle traits. What scientists discover in another species can apply to beef cattle genetics as well.
“It turns out that many genes and their functions are shared between mammals. A good example of this occurred with the ‘double muscle’ trait in the late 1990’s,” says Heaton. “It was first discovered in the mouse myostatin gene by researchers studying a mouse model of human muscle disease. Within weeks of the mouse report, several laboratories (including those at USMARC) sequenced the myostatin gene in cattle that had the double muscle trait and found similar types of mutations. These cattle mutations were shown to cause the double muscle trait. Today, using the set of online genomes that we have made available, any interested researcher could view the myostatin sequences of cattle and find the double muscle mutations in a few hours.”
Discoveries like this also improve the quality of the DNA testing beef producers use by adding new gene mutation identification to those tests. Heaton and his team provide the DNA they use to DNA testing companies so that they can check that their in-house DNA tests are predictably working and providing reliable outcomes. New mutation discoveries can help explain why some tests don’t have expected results.
This was the case when DNA sequencing by USMARC helped identify a variant in the black coat gene in some Limousin cattle that resulted in red calves in situations where tested homozygous black bulls and red cows should have had black calves. The USMARC scientists were able to look at their 96-bull DNA sequence and see that there was a difference between some of the Limousin bulls’ red-black coat color gene, which then allowed the DNA testing company to redesign their test to be truly accurate.
The online resource allows scientists to make valuable discoveries about genetics and disease that are economically, or otherwise, important. For example, already strides have been made in understanding brisket disease, otherwise known as pulmonary hypertension and right-heart failure. Brisket disease is thought to predominantly impact cattle at higher elevations, and research from Vanderbilt University Medical School recently identified a gene variant that may play a key role. Using this online resource, Heaton analyzed the same gene and found additional mutations that may also be contributing to cattle disease at lower elevations. The search for genetic risk factors affecting brisket disease is ongoing.
Being able to identify cattle genes or disease genes like this that are “bad” is useful to producers in more ways than one. The more we know about our animals and what they are susceptible to, the more we can accurately predict outcomes and adjust breeding decisions to reflect the outcomes we really want. Genetic tests that use information from the most updated cattle genome will help identify genes for disease, as well as those that impact production traits. But even if you end up having some “bad” genes in your herd, don’t be discouraged.
“The good news is that when individuals with an undesirable gene variant are identified, there is an opportunity for management,” concludes Heaton. “How producers decide to use that information depends on the specifics of their operation and their objectives. In general, for high impact disease mutations, the aim is to begin reducing the proportion of high-risk animals compared to the low-risk animals. This can be accomplished selecting bulls that have a reduced number of known disease mutations. Unfortunately, not many of these types of disease-causing mutations have been identified yet. Hopefully, this resource will help speed the discovery process.”
The Internet, for all its faults, is a place where we can work together. When we do, science can work for us, and then everyone in the beef industry comes out on top.
Infectious Disease Genetics Challenging
Studying the genetics of infectious disease is particularly challenging.
“First, you’re dealing with a second genome (i.e., the pathogen’s), and its genome and biology may not be well understood,” explains USMARC microbiologist Michael Heaton, PhD. “Second, since pathogens are microscopic, it’s difficult to tell which animals have been exposed to the pathogen, and which ones have not. This means that a genetically susceptible animal looks the same as a genetically resistant animal unless they get equal exposure to the pathogen. This makes it difficult to study real-world animal disease cases on a grand scale. It can be done, but it’s complicated.”
Scientific discoveries that come from these studies can have a big impact because disease treatment and prevention are expensive in time and resources, even if they only affect a relatively small number of each herd. As a nation of cattle, the importance of studying the smallest parts of life can have a huge influence.