AMES, IA – “This effort is a culmination of many years of dreaming about such an opportunity and finally getting access to the data and funding to make it happen,” said James E. Koltes, associate professor of animal science at Iowa State University. 

Koltes is referring to a new USDA-supported project he is leading with colleagues at Iowa State and several partner institutions to create a systematic catalog, or encyclopedia, of the DNA netherworld scientists call “genetic regulatory regions” for livestock species. The research sets the stage for important discoveries by identifying regulatory DNA variation that could be useful in breeding for improved animal efficiency and health. 

“We have known for years that most of the genetic variability in traits useful for breeding is not actually located in genes,” Koltes said. “Much of the DNA in regions outside of genes has been thought to be basically junk, but research is showing that some of it has important functions – and contains heritable genetic or epigenetic variation that alters the animals’ appearance and performance.”

Epigenetic variation refers to chemical modifications to DNA due to factors such as diet or environmental conditions that modify how genes are expressed yet do not change the DNA structure, Koltes explained. This includes complex traits like body weight or even characteristics that make a species a species. 

These gene-devoid regions are thought to comprise more than 90% of the animal genome. Studies in humans and rodents, including those by the ENCODE Consortium, indicate that DNA regulatory regions can govern how genes are turned on and off, controlling important growth processes across different stages of an organism’s life and differentiating tissue and cell types.

“I also work on understanding how genetics impacts variation in feed efficiency from animal to animal in dairy cattle,” Koltes said. “That is a complex trait, which is likely regulated in part by DNA regulatory regions that lie outside of what we have traditionally thought of as genes.”

Koltes said the new grant will focus on cattle, pigs and sheep, though the software the team will use to catalog the DNA elements could work for other species. Their ultimate goal is to help accelerate genetic improvements through development of new “open-source” annotation data sets that assign known or possible functions to a specific DNA sequence location, providing the first map of livestock regulatory functions for several species, with an online website to serve as a home for the information and training to support its sharing. 

“In addition to these useful tools, we are really digging into some novel science with potential to move rapidly into application,” he said. 

The project has just received $800,000 for the next three years from the National Institute of Food and Agriculture under USDA’s Agriculture and Food Research Initiative. The new grant was born out of an Agricultural Genome to Phenome Initiative (AG2PI) seed grant project, Koltes said. 

He will work with other Iowa State animal scientists, including Distinguished Professor Chris Tuggle, a leader in the Functional Annotation of ANimal Genomes (FAANG), an international coordinated effort to create and share much of the high-quality information on farmed and companion animal genomes being cataloged in the new project; and associate scientist Zhiliang Hu, a lead developer of tools for animalgenome.org.

Other partners are: 

• Zhiping Weng, Li Weibo Chair in biomedical research at the University of Massachusetts Chan Medical School, a leading data scientist on ENCODE and developer of SCREEN, a key software to be used for livestock in this project. ENCODE, which began about a decade ago with a focus on the human genome, is a similar project to FAANG for livestock. 
• Mallory Freeberg, Human Genomics Team leader, the European Bioinformatics Institute and Molecular Biology Laboratory (EMBL-EBI).
• Brenda Murdoch, associate professor in the Department of Animal, Veterinary and Food Sciences at the University of Idaho. 
• Chris Elsik, professor of animal science at the University of Missouri. 

Iowa State University Associate Professor James Koltes holds a SNP (single nucleotide polymorphism) chip. These glass microscope slides allow for testing thousands or even millions of single DNA bases in the genome for use in breeding or to identify genetic regions that impact traits important in agricultural species. Identifying regulatory regions will help refine the tests used on these chips to allow for “precision breeding” and new research to study how gene function is regulated across all genes in the genome. Photo by Whitney Baxter.

(contributed press release, ISUCALS)