by Roberta Pattison
Exploring the genetic makeup of other species helps scientists to explain many of the mysteries still surrounding human disease — but those explorations also generate significant breakthroughs in animal health research. So when the National Human Genome Research Institute (NHGRI) recently announced its plans to sequence and map the entire equine genome, the news was welcomed by all scientists studying genetically-linked conditions in horses — including researchers based at the Western College of Veterinary Medicine in Saskatchewan.
Two of those scientists are Drs. Katharina Lohmann and Lynne Sandmeyer whose Equine Health Research Fund-backed studies may greatly benefit from NHGRI’s high density sequencing of the equine genome.
Lohmann, a specialist in veterinary internal medicine and an associate professor in WCVM’s Department of Large Animal Clinical Sciences, is investigating genetic risk factors for the development of endotoxemia. Although the first part of Lohmann’s study is too far advanced to benefit from the genome sequencing project, her current research into genetic factors contributing to the development of sepsis in foals is just getting underway.
The study involves looking for minute gene sequence variations called single nucleotide polymorphisms or SNPs in septic and non-septic foals. Lohmann and her collaborator, Dr. Michelle Barton of the University of Georgia, plan to collect DNA samples from next spring’s foal crop for this study. “You might say I am working at the opposite end of the scale to the genome project,” explains Lohmann. “I start with an interesting gene and work backward.”
Lohmann believes that with the genome map in place, she and her research team will likely be able to save time and money: “The important thing about the sequencing, which will include identifying SNPs, is that there will be more information available. That has been a significant restriction up to now. There’s already an SNP database for other species, and it will be great to have access to an equine one. For now, my work still includes the first step of finding the SNPs in the first place.”
Sandmeyer is a veterinary ophthalmologist who is studying congenital stationary night blindness (CSNB) in Appaloosa horses. As her ground-breaking project has helped to confirm, the condition has an hereditary basis. Although Sandmeyer is concentrating on the ophthalmologic aspects of the disease versus its genetic origin, she appreciates that the sequencing of the equine genome will almost certainly have an impact on her work — and the ultimate goal of developing gene therapy for CSNB.
“A lot of work has already been done locating the Lp (leopard complex) gene which is responsible for the Appaloosa pattern and believed to be linked with CSNB. The genome study is important because it will provide a ‘normal’ gene for comparison,” explains Sandmeyer.
Sandmeyer’s CSNB study is part of The Appaloosa Project — a North American research initiative that’s designed to investigate the nature of Appaloosa genetics. Sheila Archer, the phenotype researcher and co-ordinator of The Appaloosa Project, agrees that the sequencing of the horse will significantly increase the speed in which researchers can isolate the Lp mutation.
“Up to this point, we have had no example of ‘normal’ for the candidate genes we selected as possibly being the loci (a locality or place) at which the Lp mutation exists. Having the sequence for these genes of interest means we will have a reference to which we can compare. Looking for a mutation is much easier when you can line it up beside what’s right.”
NHGRI plans to complete its sequencing of the equine genome by this fall. Pulling together the millions of pieces and organizing them into a readable map will take considerably longer, but researchers will soon have an amazing wealth of new genetic information at their fingertips.
“It’s not the answer to everything, but it provides us with an important new resource. It’s also great that the horse has been chosen because horses are so often ignored when it comes to this kind of research,” says Lohmann. “This will certainly make a difference to our work from now on.”
Published with permission from Horse Health Lines, publication for the Western College of Veterinary Medicine’s Equine Health Research Fund. Visit www.ehrf.usask.ca for more information.
