Newly Sequenced Bovine Genome Aids Health Research

Newswise — Researchers for the Bovine (Cow) Genome Sequencing Project, including a team of veterinary and animal scientists at the University of Massachusetts Amherst, announced today that the first full genome of a female Hereford cow named L1 Dominette has been sequenced. Dominette's genome is the first ever livestock animal to be sequenced. Other mammal genomes mapped to date belong to humans or laboratory animals. Two papers on the bovine sequencing project appear in the April 24 issue of the journal, Science.

This accomplishment of more than 300 scientists in 25 countries provides new information about the evolution of cattle dating back about 300 million years, as well as keys to cattle-specific biology. Of particular interest to UMass Amherst faculty members Cynthia Baldwin and Janice Telfer and research scientist Carolyn Herzig, as members of the genome project's adaptive immunity group, is the bovine immune system and its large numbers of a type of white blood cell known as a gamma delta T cell. Understanding these could give Baldwin, Telfer and Herzig critical information on how to fight diseases such as tuberculosis and leptospirosis, which can drastically cut reproductive success in cattle.

With a high prevalence in United States animals, leptospirosis and tuberculosis are of major economic importance to dairy and beef producers. "The genome sequences give us another tool in the box for understanding the ruminant body's response to infectious disease," Baldwin points out. "Through this study we've annotated hundreds of immune function genes, including about 50 cytokine genes, as well as the bovine gamma delta T cell co-receptor genes."

Annotating genes means that Herzig spends hours at her computer piecing genetic "words" and "phrases" together into meaningful "sentences" within a framework from the millions of scrambled code or "letters" in the genome. Without this organizational step, the genome would not be useful to biological researchers. Although the work took six years for dozens of research groups to complete, that's considerably better than the decades estimated for a single lab to do the entire job, Baldwin and Telfer note.

With the new knowledge about specific cattle gene locations and combinations they've gained over the last six years of annotation, Baldwin and Telfer plan next to study the relatively large numbers of immune system gamma delta T cells found in young lambs and calves "to figure out how they work in cattle," Telfer notes. Similar genes exist in humans and other mammals, and understanding how they work in cattle will provide insight into their function in human immune response. Until the sequencing of this bovine genome, cows' specialized and very ancient immune adaptations had remained a "black box" into which no biologists could see, the researchers add.

As one of the lead analysts, Harris Lewin of the University of Illinois points out that researchers with the international project were "surprised to find that, like humans, duplicated segments appear to have played a major role in the rearrangements of chromosomes in the cattle lineage." Some of these changes help to explain how cattle convert low-quality forage into milk, which contains an anti-microbial protein that helps protect their calves.

Further, new tools such as gene chips derived from the new genome could provide a way to breed more energy-efficient animals with a smaller environmental footprint, in particular lower greenhouse gas emissions, the authors point out. Another of the international team members adds that it appears the cow has "significant rearrangements in many of its immune genes and enhanced innate immune defense capacity," perhaps evolved to counteract infection risk posed by so many bacteria that help with digestion in the largest section of the compartmented ruminant stomach.

The UMass Amherst animal scientists plan to begin developing potentially more effective vaccines against diseases caused by intracellular bacteria, protozoa and viral infections. As Baldwin explains, "The gamma delta T cells seem to be key to the immune response in cattle. Knowing the genome sequence tells us what genes are there, what to measure in blood samples and the sort of molecules to test for. Overall, we can now hope to get a far more precise understanding of the animal's response to disease."

In general, project researchers on the international team conclude that the bovine genome of at least 22,000 genes is more similar to that of humans than to that of mice or rats. Most cattle genes have corresponding human genes, but their organization is different in some areas, Baldwin adds. Nevertheless, this similarity between humans and cattle, closer than between mice and humans, may mean that these animals are a better model for studying human disease.

The evolution of humans and cattle intertwined between 8,000 and 10,000 years ago, study leaders note, and today there are more than 800 cattle breeds selected by humans for economic, social and religious reasons. The genome mapping project also looked at genetic diversity among different domestic populations including humpless cattle most familiar in the United States and Europe, in African zebu, water buffalo and other types from India, Africa and Asia.

Funding was provided by an international group that included the National Human Genome Research Institute, the United States Department of Agriculture, state funds from Texas, North and South Dakota, several Canadian provincial research institutes, several United States and Australian foundations, cattle associations and companies, plus research institutes in Norway, New Zealand, Kenya, Italy, Brazil and France, among others.

The full report is available at www.sciencemag.org.