A multi-institutional team of researchers has created a new and improved genetic map for the laboratory rat, a cornerstone in medical and scientific research. Known as GRCr8, this updated genome assembly enhances the ability to study human diseases, behaviors and genetic traits more precisely.  

The study titled “Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding” — in concert with the University of Texas-Houston, University of Louisville, Texas A&M, Wellcome Sanger Institute, Medical College of Wisconsin, University of Tennessee and National Center for Biotechnology Information — was published in Genome Research. 

Ted Kalbfleisch, University of Kentucky Gluck Equine Research Center director of graduate studies and professor at the Martin-Gatton College of Agriculture, Food and Environment and one of the lead scientists, highlighted the study’s impact.  

“The laboratory rat has been a critical model for studying human health and disease for decades,” he said. “With GRCr8, we now have a more precise and complete genetic picture, which can improve how we use rats to understand complex conditions known to affect humans similarly.” 

Why rats matter in research 

Rats have long been a staple in biomedical research because their biological and behavioral characteristics mirror many aspects of human health. Their use spans studies on addiction, cardiovascular diseases and even psychological conditions like anxiety and depression.  

“The previous genome maps gave us a solid foundation, but they were incomplete in some critical ways,” Kalbfleisch said. “With GRCr8, we’ve addressed those gaps, enabling researchers to dig deeper into areas like genetic mutations, gene regulation and disease mechanisms.” 

One of the most significant updates to the genome maps includes the addition of more than 1,100 new protein-coding genes that were previously unidentified. These newly mapped genes offer insights into biological functions that could be vital for understanding diseases and traits, such as those related to reproductive health or immune responses. 

Beyond just improving the structure of the rat genome, GRCr8 provides valuable new information about how genes function and work together. The scientists used special techniques to check the accuracy of the genome and study how genes behave in different parts of the body, like the brain, liver and reproductive organs. 

“This tool helps researchers not only find genes but understand what they do,” said Kai Li, the lead author on the paper and a UK graduate student. “For instance, the mapped sequence for the Y chromosome is increased threefold in this assembly over the previous version, which could help with research into fertility and reproductive health.” 

To ensure the genome map was accurate, scientists tested using advanced computer tools and compared it to older versions. These tests showed that GRCr8 is highly reliable and complete, making it a trusted resource for researchers everywhere. 

Implications for medical and agricultural research 

The improved genome map provides a sturdy foundation for scientists exploring a variety of diseases. Researchers studying genetic disorders can now pinpoint mutations with greater precision. Simultaneously, those investigating complex traits like addiction or stress resilience can rely on a more detailed view of the underlying biology. 

Kalbfleisch likened the new genome to a more reliable guidebook for navigating genetic landscapes. 

“For example, studies into cardiovascular diseases can now incorporate previously missing genetic data, improving the understanding of how certain genes influence heart function,” he said. “Similarly, behavioral studies on addiction or social interactions can explore their underlying genetic networks in greater depth.” 

As the prices to sequence and assemble genomes continue to plummet, building and analyzing genomes is becoming much more common. With this project, and others like it in the horse and other agricultural animals, the Kalbfleisch lab is in the vanguard of genetic scientists working to understand how the entirety of an animal’s genome supports its health, wellbeing and performance. The Kalbfleisch lab is currently working to build these high-quality genomes across 12 breeds of horse, a zebra, donkey and Persian onager. He is also participating in a similar effort for 234 species of ruminant including cattle and sheep. 

Looking ahead 

While GRCr8 represents a significant leap forward, the work is far from finished. Kalbfleisch said researchers are already exploring ways to refine and expand the genome further. New sequencing technologies, such as ultra-long read sequencing, could provide even more detail — resolving remaining challenges with assembling highly complex or repetitive regions. 

“This is a milestone, but it’s part of a broader journey,” Kalbfleisch said. “The more we refine these tools, the better we can understand the genetic basis of health and disease — not just in rats, but in humans too.” 

The GRCr8 genome is now publicly available, allowing scientists to incorporate its data into their work. As this resource continues to drive discoveries, it will enhance how researchers approach everything from drug development to understanding the genetic roots of disease. 

“Our goal has always been to equip researchers with the best possible tools,” Kalbfleisch said. “GRCr8 is a step forward, and we’re excited to see what the scientific community achieves with it.” 

Research reported in this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number R01HG011252. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.  

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Writer: Jordan Strickler, jstrickler@uky.edu          

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