Researchers Report Construction of Genetic Map for Dogs

Researchers at the Fred Hutchinson Cancer Research Center in Seattle and the James A. Baker Institute for Animal Health at Cornell's College of Veterinary Medicine are reporting the development of a framework reference map of the canine genome. The article appears in today's issue of Genomics, published by the Academic Press.

The ultimate goal of canine genome research is to find all the genes in the DNA sequence of dogs and make this information available to others to develop tools to better diagnose disease well before the appearance of symptoms. It is believed that dog genetics offers the hope of discovering the genetic basis of both development and behavior in a variety of mammalian species including human.

"The notion of a canine genetic map had been proposed by the genetics community years ago; over the last three years we developed the markers to serve as the cornerstone of the map," said Elaine Ostrander, PhD, lead investigator and molecular biologist, Hutchinson Center." Cornell became the catalyst that allowed assembly of the map to begin in earnest two years ago."

"We were able to provide a number of highly informative pedigrees of dogs that, for several years, had been bred specifically for genetic studies such as these," said Gustavo Aguirre, VMD, PhD, professor of ophthalmology and director of the Center for Canine Genetics and Reproduction at Baker Institute.

The map covers most of the canine genome and represents a major step toward the completion of a more comprehensive canine genetic map. It was constructed from 150 highly informative markers, known as microsatellite markers, developed by the Ostrander group and typed on informative pedigrees developed by the Cornell team. The linkage panel used included information from 17 three-generation pedigrees with genetically distinct backgrounds, a total of 212 individuals.

The development of a canine genetic map is of particular importance, not only in solving questions of inheritance in dogs, but in humans as well. Purebred dogs, though all of one species, in practice represent a multitude of closed breeding populations. Many of the genetic diseases that proliferate in inbred dogs also occur in the human population, but are difficult to trace genetically, according to Aguirre, because the high degree of genetic diversity and low number of offspring in human families make informative pedigrees a rarity. These diseases include cancer, epilepsy, retinal degeneration, bleeding disorders, skeletal malformations, and a host of others. Dogs represent a unique genetic resource with each of several hundred breeds exhibiting distinct physical and behavioral traits with remarkable consistency among its members.

"In spite of their obvious breed-specific differences, all dogs belong to one species, and can therefore crossbreed successfully. A great deal of genetic information can be gained by analyzing crosses between two highly distinct breeds of dogs," said Aguirre. "This information will potentially lead to an increased recognition of the role inheritance plays, not only in appearance or in susceptibility to disease, but also in behavior, both in humans and canines.î

In a second paper published in the journal, the two groups describe the construction of a dog-rodent hybrid cell panel to aid in determining the order and spacing of genes and traits of interest on the chromosomes of the canine genome.

Both papers are the result of an unusual and highly productive collaboration between the two major canine genetics groups in Seattle and Ithaca, each of which brought a unique set of resources and talents to the venture.

The Hutchinson Center is one of 28 comprehensive cancer research centers, as designated by the National Cancer Institute. Using basic and applied research, the Center's mission is to eliminate cancer, and other potentially fatal diseases, as a cause of human suffering and death.

In 1951 the James A. Baker Institute for Animal Health established the first laboratory in the world dedicated solely to addressing the health needs of dogs through basic and applied research. The Institute is renowned for its contributions to the control of canine infectious diseases through the development of vaccines against canine distemper, infectious hepatitis, parvovirus, and other diseases. The Institute is part of the College of Veterinary Medicine at Cornell University, established in 1894; the mission of the College is to advance animal and human health through education, research, and public service.

The project was conducted by Dr. Ostrander and her associates at the Fred Hutchinson Cancer Research Center as a continuation of work that she had initiated with Jasper Rine, PhD, professor of genetics, department of molecular and cell biology, University of California, Berkeley. Collaborating with Ostrander's team was a team of Cornell researchers led by Dr. Aguirre. Other members of the Cornell team included Gregory Acland, BVSc, a veterinary ophthalmologist and senior research associate in genetics; and Kunal Ray, MS, PhD, senior research associate in molecular genetics.

This research was supported by The Canine Health Foundation of the American Kennel Club, the Wellcome Trust, the Foundation Fighting Blindness, Morris Animal Foundation, the American Cancer Society, and the National Institutes of Health.

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