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Of Mice and Men (and Beef Cattle)

What do beef cattle, mice and humans have in common? If you said they all have functional variants, you either peeked at the answer or you’re part of the Genome Alberta beef cattle project. As they seek to apply genomics in improving meat quality and feed efficiency, researchers know the importance of functional variants – variants that affect genetic traits – and the value of a multi-species approach in achieving success.

“One challenge we face when working with DNA sequence data is the sheer number of variable positions we observe in the genome,” said Dr. Paul Stothard, Associate Professor - Bioinformatics and Genomics, Department of Agricultural, Food and Nutritional Science (AFNS) at the University of Alberta.

30 million reasons to find a better way

“With cattle there are more than 30 million sites in the genome that differ among individuals,” said Stothard. “We want to determine which of these sites contribute to certain characteristics such as presence of disease, coat color, animal size and feed efficiency.”

Even with the most dedicated researcher, sifting through that many variations is grounds for stress leave, so Dr. Stothard and his team are finding ways to expedite the process.

“One strategy we employ to locate functional variants is using the extensive information collected on the function of genes and the impact of mutations in other species like humans and mice. We have now developed software to help make use of this data.”

Gene shopping

For each sequence variant they encounter in cattle, they use the software to determine the corresponding position in the human genome. They can then search a variety of databases to see what traits in people have been associated with changes to that genome site.

“We confirmed that this approach can work by identifying a mutation in cattle that causes a condition called leukocyte adhesion deficiency. Our software was able to flag the causative variant in cattle by using knowledge about the disease in humans.”

A prime example of the software in action is the recent genome sequencing of a calf with Osteogenesis Imperfecta (OI), a genetic disorder that affects the skeleton and is caused either by a mutation inherited from a parent or a new mutation in the affected individual.

 “The software identified the disease-causing variant in the calf on the basis of a very similar mutation in humans that caused OI. It then determined that this mutation was a new one in the calf rather than inherited. Figuring out whether a case of OI is inherited is important as it can lead to strategies for reducing the prevalence of the disease.”  

Pick a species, any species

In the case of feed efficiency, a key focus of this project, finding functional sequence variants in cattle using human data can be more difficult as that trait isn’t directly studied in humans. Thus the team has begun incorporating more species into their analysis, such as genes and mutations reported in chickens and pigs that relate to feed efficiency.

Clearly, the researchers’ efforts have involved some out-of-the-box thinking that they hope will pay off in the end.

“In terms of the big picture, this will speed up the process of identifying functional variants and explaining important traits in cattle. We can then use those variants to save producers money on feed costs and reduce the environmental footprint of beef production.”

As it turns out, genetic progress is not just about collaboration among researchers, but also among species, and why not? We all share the planet, so we might as well work together to preserve it.

Of Mice and Men (and Beef Cattle)

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