Mapping the way forward for equine research

Dr. Jonah Cullen, CVM alumnus and postdoctoral researcher in the Equine Genetics and Genomics Laboratory, received $218,000 from the USDA National Institutes of Food and Agriculture to develop genetic tools called pangenome and pantranscriptome graphs for horses—a first-of-its-kind undertaking for the species.

Genetic research has historically relied on reference tools that are based on only one or a handful of individuals—and are therefore unable to truly capture the genetic diversity of a species. But the decreasing cost of genetic sequencing technologies, combined with developments in advanced computational methods means that it’s now possible to develop reference tools that are constructed from the genetic profiles of hundreds or thousands of individuals. These tools provide researchers with a much more detailed genetic map of a species, enabling a more nuanced understanding of similarities and variations among individuals and breeds.

Pangenome graphs, for example, allow us to understand the complete genetic landscape of a species by identifying core genes shared among all individuals as well as genes unique to certain individuals or subpopulations. They’re useful tools for studying evolutionary dynamics, adaptation, and genomic variation within a species. By analyzing pangenome graphs, researchers can identify genes associated with specific traits or diseases and understand how genetic diversity contributes to phenotypic differences—differences that we can see, measure, and detect—among individuals.

Pantranscriptome graphs reveal the diversity in gene expression patterns—in other words, which genes are active and how much they’re being used in a population or under certain conditions. Researchers can use pantranscriptome graphs to identify key genes or pathways involved in biological processes and to uncover potential targets for new disease treatments. 

These tools are essential for advancing our understanding of the complexity of living organisms at the molecular level, shaving off years of complicated, time-consuming work for genetics research and enabling accuracy that would not have previously been possible. Pangenome and pantranscriptome graphs exist for humans and some other species—and they’re “the future of agricultural genetic research,” says Cullen. But no such tools exist as yet for horses.

Building the tools requires both benchtop genetics work in the lab, as well as the computer work to develop the methods and code that are the tools’ architecture, and Cullen is focused on the latter. “We’re developing a resource that can be used anywhere in the world—people can compare their own data to the pangenome, for instance, to hone in on a particular disease they’re interested in,” he describes. And the addition of others’ data helps to make the tool increasingly robust. “But we’re also making something that’s highly reproducible so that other groups and institutions can use these methods to build their own pangenome, say of a larger group or a breed.”

Cullen works closely with the Minnesota Supercomputing Institute, along with his mentors Dr. Molly McCue, professor in CVM’s Department of Veterinary Population Medicine, and Dr. Ted Kalbfleisch, professor of Veterinary Science at the University of Kentucky. “Receiving this award to generate the first draft of the equine pangenome will be an important step forward in our understanding of equine genetics,” describes Cullen. “This pangenomic representation will open new avenues for research and discovery that were previously unattainable.”