By Blake Jackson
University of Kentucky scientists at the Martin-Gatton College of Agriculture, Food and Environment have contributed to a nearly complete genetic map of the brown rat, strengthening the animal’s value as a model for studying human health and disease, according to Jordan Strickler, Agriculture Communications Specialist at the University of Kentucky.
Published in Cell Genomics, the study provides a more detailed view of rat DNA by comparing eight laboratory rat strains. Researchers used advanced sequencing technology to examine sections of the genome that were difficult to decode with older methods, particularly repetitive DNA sequences.
Rats have been important research animals for more than a century. Their larger size and complex behaviors make them particularly useful for studies involving aging and other aspects of human health.
Ted Kalbfleisch, Ph.D., a Professor in the Department of Veterinary Science at the Maxwell H. Gluck Equine Research Center, participated in the research.
“One of the most powerful mechanisms in genomic evolution is the replication of small, gene-containing regions of the genome,” Kalbfleisch said.
The researchers created a telomere-to-telomere (T2T) genome assembly, producing a substantially more complete representation of the rat genome. Sixteen of the species’ 22 chromosomes were assembled continuously from end to end.
The number of remaining gaps dropped to seven, compared with 164 in an earlier high-quality reference genome. The new assembly also incorporated about 60 million additional DNA building blocks.
The improved map enabled researchers to identify previously overlooked genetic material, including potential gene-coding sequences and previously unknown gene regions. Information from 19 rat tissues helped researchers examine how these sequences function across the body.
The study also uncovered differences in the way rat X and Y chromosomes appear to pair during sperm production. Unlike humans and mice, where matching regions contain genes, the corresponding rat region primarily consists of repetitive DNA.
Researchers then combined data from the eight strains to build a rat pangenome. This approach allows scientists to compare genetic variation across multiple laboratory strains rather than relying on a single reference genome.
Significant differences were found in regions associated with immune-system function, potentially helping explain why strains respond differently to diseases.
“Once duplicated, either the original gene or the copy is free to change since the other copy is there to still perform its function,” Kalbfleisch said.
The findings could help researchers select appropriate rat strains, better interpret experimental results, and identify potential disease-related genetic changes.
Kalbfleisch noted that the improved genomes may also help scientists study structural variants and understand how duplicated genes influence disease or protect tissues from damage.
The researchers said expanding the pangenome with more genetically diverse rats could provide an even broader understanding of the species and its usefulness in human health research.
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