After splitting genetically from wolves about 135,000 years ago, dogs have followed
humans through every step in their cultural and social development, from hunting
and gathering to agricultural societies, from the farm to the city and suburb.
The dog has helped domesticate sheep and cattle, served as a guard, beast of
burden, guide, and companion capable of easing the pain of loneliness. So closely
entwined are their lives that a number of evolutionary biologists argue that
dogs and humans have evolved together. Over the past decade, a loose-knit band
of scientists in laboratories in the United States and abroad have worked diligently
to bring man's esteemed friend into the postindustrial age of the genome. Compared
with the Human Genome Project, the dog effort resembles a poorly capitalized
cottage industry, strung together with occasional grants rarely amounting to
more than a few million a year. But researchers have recently begun to speed
the search for disease-causing genetic mutations in dogs, which often have human
counterparts. "We are a small group of people who want to map the dog genome
for a variety of reasons, including the study of human genetic diseases," said
Dr. Gregory M. Acland, a research scientist at the James A. Baker Institute
for Animal Health at Cornell University. "The dog might also be the best model
for looking at the genetics of behavior. Beyond that, most of us just like dogs."
The dog seemingly changed little in appearance from the wolf until some 15,000
years ago, when it began to move with humans into more permanent settlements,
according to Dr. Robert K. Wayne, an evolutionary biologist at the University
of California at Los Angeles. Since that time, through conscious and unconscious
selection, humans have created more than 400 breeds with greater variability
in size and shape than any other species, with the exception of humanity itself.
Breeders have traditionally relied on the "founder effect," mating popular sires
to numerous females to spread their characteristics rapidly, and inbreeding,
mating related descendants of that dog to fix the traits they want, said Dr.
Donald F. Patterson, a professor of medicine and medical genetics at the University
of Pennsylvania. If a popular sire also carries a genetic defect, it too spreads
rapidly through the line. For the past 20 years, Dr. Patterson has maintained
a database now listing 370 genetic disorders in dogs, with 5 to 10 new ones
added each year. (By comparison, there are some 5,000 identified human genetic
disorders.) Like behavioral and physical characteristics, those canine diseases
and the responsible mutations tend to segregate according to breed, with many
prone to more than one affliction. Thus, progressive retinal atrophy, a form
of hereditary blindness, is caused in different breeds by a mutation to any
one of at least seven different genes, according to Dr. Gustavo Aguirre, a professor
of ophthalmology at Cornell's Baker Institute. In 1998, his research team, including
Dr. Acland, located a marker for the gene causing heredity blindness in Labrador
retrievers, Portuguese water dogs, poodles, American and English cocker spaniels,
and possibly five other breeds. (Because of hybrid vigor, mixed breeds suffer
from genetic disease far less often than their purebred cousins.) Progressive
retinal atrophy is the equivalent of retinitis pigmentosa in humans. In fact,
nearly 60 percent of the genetic disorders in dogs correspond to genetic diseases
in humans, Dr. Patterson said, including epilepsy, cancer, deafness, blindness,
autoimmune disorders, congenital heart disease, skeletal malformations, neurological
abnormalities and bleeding disorders. "The closed gene pools and extensive pedigrees
of purebred dogs make them ideal for mapping genetic diseases that have been
intractable in humans," said Dr. Elaine Ostrander, head of the human genetics
program at the Fred Hutchinson Cancer Research Center in Seattle. Dr. Ostrander
is studying the genetics of breast and prostate cancer. In 1991, Dr. Jasper
Rine, a genetics professor at the University of California at Berkeley, and
Dr. Ostrander, then a staff scientist in his laboratory, conceived of using
the dog to examine how genes shape behavioral and physical characteristics,
as well as disease. In the process, they would establish a genetic map that
could be linked to that of humans, with whom dogs share 80 to 90 percent of
their genetic code. The project's initial goal was to study inheritance of the
Newfoundland's perceived love of water and the border collie's habit of herding
sheep. So the researchers crossed a border collie and Newfoundland but abandoned
that program after two generations. Dr. Rine is no longer involved, but Dr.
Ostrander has continued as coordinator of the Dog Genome Project. She and a
core group of 15 researchers from laboratories in the United States and Europe
have created and are rapidly expanding several different maps showing the location
of hundreds of signposts, or markers -- genes and microsatellites, which are
repetitive strands of genetic code, with an unknown meaning, that are useful
for tracking familial inheritance of genetic traits and finding the genes. They
have also created a database containing cloned stretches of dog chromosomes.
At any one time, 50 to 100 laboratories are drawing on it and contributing new
data, Dr. Ostrander said. Reviewing progress for the March 2000 issue of Trends
in Genetics, Dr. Ostrander and her co-authors, Dr. Patterson of Penn and Dr.
Francis Galibert of the University of Rennes in France, estimate that most of
the dog genome is now assigned to its corresponding part of the human map. But
assigning the markers used in the mapping to specific canine chromosomes, an
essential process to exploiting the data's full potential, has proceeded more
slowly. Although the canine genome, like that of humans, is estimated to have
three billion base pairs of DNA and 100,000 genes, they are distributed over
78 chromosomes, compared with 46 in humans. To date, only about two-thirds of
the dog chromosomes have been identified, many of them by the Animal Health
Trust in England, and fewer than half of the existing markers have been assigned
to chromosomes. Incomplete as it is, the material that does exist has opened
a new season in the hunt for defective genes. Since 1989, scientists have identified
and characterized 21 specific canine disease genes, half of them since 1996,
and markers have been found for others, according to Dr. Patterson. Among the
most spectacular was the discovery in 1999 of the gene and mutations responsible
for narcolepsy in Doberman pinschers, Labrador retrievers and dachshunds by
Dr. Emmanuel Mignot, an associate professor of psychiatry at the Stanford University
School of Medicine. "The dog unlocked the mystery of narcolepsy in humans so
that we can now work to develop new treatments and better understand sleep,"
Dr. Mignot said. Given the pace of discovery, Dr. Acland predicts that "all
single-gene disorders in the dog will be eliminated through genetic testing
and selective breeding within the next 20 years." The American Kennel Club's
Canine Health Foundation and 60 breed clubs are supporting much of that work.
Even disorders caused by unknown combinations of genes may soon be better understood.
Dr. George Brewer, a professor of human genetics and internal medicine at the
University of Michigan, believes he will begin to unravel the genetics of hip
dysplasia, a disabling form of osteoarthritis that afflicts many breeds, in
the next year or two. Encouraging as those advances are, the Dog Genome Project
has yet to contribute significantly to its initial goal of understanding morphology
and behavior. Dr. Rine said that with the human and mouse projects drawing to
a close, it was time to sequence the entire dog genome. That would not only
accelerate the search for individual genes but help scientists understand more
complicated questions about the nature of the dog, its incredible talents and
the origin of breeds. Copyright 2000 The New York Times

Dogs and Humans Are Seen as Partners in Evolution
April 4, 2000
By Mark Derr