A brown rat (Rattus norvegicus). Credit: Dunpharlain
Researchers have assembled the most complete genetic profile of the brown rat to date, giving scientists a far more accurate reference for studying the genetic roots of conditions such as heart disease, kidney disease, high blood pressure and stroke.
For the study, published in Cell Genomics, researchers used a technique called long-read sequencing to read unusually long stretches of DNA at once. That allowed the team to piece together a complete, gap-free sequence of all 22 rat chromosome pairs, stretching from one end of each chromosome to the other—something previous, more fragmented rat genome maps could not achieve.
The finished map turned up more than 60 previously unknown genes, many thought to play roles in immunity, and revealed that the rat genome is more complex than scientists had realized. It also uncovered a surprising twist in rat reproduction: unlike humans and most mammals, whose X and Y chromosomes share roughly 20 genes that let the two chromosomes pair up and replicate, brown rats have lost those shared genes entirely. The genes relocated elsewhere in the genome, while new sequences allow the rat's X and Y chromosomes to pair end-to-end rather than side-by-side as in other mammals.
The team also built eight separate high-quality genome assemblies from different rat strains and combined them into a single pangenome. The pangenome adds 7% more sequence than was previously known, giving scientists one place to check whether a gene of interest—and its function—differs from rat to rat.
The completed map solves a problem that had long frustrated researchers, who previously lacked the tools to make sense of duplicated or repetitive DNA regions.
“We know that there are genetic causes of diseases, but when we try to find out where in the genome they're coming from, we kind of get lost,” said study author Peter Doris, director of the Center for Human Genetics at UTHealth Houston. “Until now, it has been extremely difficult to recognize genetic differences because the assemblies that we were working with had missing pieces.”
Data from University of Texas Health Science Center