Researchers Report Construction Of Genetic Map For Dogs

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

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

"We were able to provide a number of highly informative pedigrees of dogsthat, for several years, had been bred specifically for genetic studiessuch as these," said Gustavo Aguirre, VMD, PhD, professor of ophthalmologyand director of the Center for Canine Genetics and Reproduction at BakerInstitute.

The map covers most of the canine genome and represents a major step towardthe completion of a more comprehensive canine genetic map. It wasconstructed from 150 highly informative markers, known as microsatellitemarkers, developed by the Ostrander group and typed on informativepedigrees developed by the Cornell team. The linkage panel used includedinformation from 17 three-generation pedigrees with genetically distinctbackgrounds, a total of 212 individuals.

The development of a canine genetic map is of particular importance, notonly in solving questions of inheritance in dogs, but in humans as well.Purebred dogs, though all of one species, in practice represent a multitudeof closed breeding populations. Many of the genetic diseases thatproliferate in inbred dogs also occur in the human population, but aredifficult to trace genetically, according to Aguirre, because the highdegree of genetic diversity and low number of offspring in human familiesmake 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 ofseveral hundred breeds exhibiting distinct physical and behavioral traitswith remarkable consistency among its members.

"In spite of their obvious breed-specific differences, all dogs belong toone species, and can therefore crossbreed successfully. A great deal ofgenetic information can be gained by analyzing crosses between two highlydistinct breeds of dogs," said Aguirre. "This information will potentiallylead to an increased recognition of the role inheritance plays, not only inappearance or in susceptibility to disease, but also in behavior, both inhumans and canines.Ó

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

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

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

In 1951 the James A. Baker Institute for Animal Health established thefirst laboratory in the world dedicated solely to addressing the healthneeds of dogs through basic and applied research. The Institute is renownedfor its contributions to the control of canine infectious diseases throughthe development of vaccines against canine distemper, infectious hepatitis,parvovirus, and other diseases. The Institute is part of the College ofVeterinary Medicine at Cornell University, established in 1894; the missionof 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 FredHutchinson Cancer Research Center as a continuation of work that she hadinitiated with Jasper Rine, PhD, professor of genetics, department ofmolecular and cell biology, University of California, Berkeley.Collaborating with Ostrander's team was a team of Cornell researchers ledby Dr. Aguirre. Other members of the Cornell team included Gregory Acland,BVSc, a veterinary ophthalmologist and senior research associate ingenetics; and Kunal Ray, MS, PhD, senior research associate in moleculargenetics.

This research was supported by The Canine Health Foundation of the AmericanKennel Club, the Wellcome Trust, the Foundation Fighting Blindness, MorrisAnimal Foundation, the American Cancer Society, and the National Institutesof Health.