Genetic Map of Dog May Help Humans

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Genetic Map of Dog May Help Humans

The decoded genome could provide insight into both species' diseases

and behaviors.

By Kaplan, Times Staff Writer

http://www.latimes.com/news/local/la-sci-dogs8dec08,0,4663383.story?

page=2 & coll=la-home-headlines

Scientists have decoded the complete genome of the domestic dog, a

milestone announced Wednesday that provides a biological roadmap for

unraveling human diseases and probing the mysterious bond between man

and his best friend.

Dozens of researchers worked for two years deciphering and analyzing

the 19,300 genes belonging to a 12-year-old boxer named Tasha. What

they found was an exceptional correlation between the DNA of Canis

familiaris and Homo sapiens, according to a study published today in

the journal Nature.

" Humans and dogs have essentially the same genes, " said lead author

Kerstin Lindblad-Toh, co-director of the genome sequencing and

analysis program at the Broad Institute of MIT and Harvard

University. " Every gene has a gene with the same function in the

other genome. "

That closeness is reflected in the numerous diseases shared by dogs

and humans, including cancer, heart disease, blindness, epilepsy and

diabetes.

Of the 10 most common diseases in dogs, eight are important to humans.

The completion of the dog genome offers the possibility that

idiosyncratic dog breeds — often specifically bred for behavioral

traits such as obedience, viciousness or docility — will help

illuminate the elusive genetic instructions that account for the

infinite variety of human personalities.

" There are angry breeds, mean breeds, calm breeds and nice breeds, "

said Hans Ellegren, a professor of evolutionary biology at Uppsala

University in Sweden. " This is now the best possibility we have to

map the genes that are involved in these traits. "

Tasha, a stout purebred female with a brown-and-white coat and

drooping jowls, was selected from 120 dogs screened by the National

Human Genome Research Institute in Bethesda, Md., because her genes

showed the least amount of variation.

Only female dogs were considered because they have two X chromosomes,

which researchers wanted to map in detail.

Scientists refused to say much about Tasha, the pet of an

unidentified family.

Her stoical photo, however, now hangs prominently on the Mammalian

Wall of Fame at the Broad Institute in Cambridge, Mass., where the

sequencing work was completed.

The researchers reported that the complete dog genome consists of 2.4

billion chemical letters — commonly known by the letters A, T, C and

G — compared with about 3 billion for humans.

In comparing Tasha's genome with genetic data from 10 other breeds,

the researchers cataloged about 2.5 million specific genetic

differences among dogs, which dictate differing sizes, proportions,

temperaments and propensity for disease.

Dogs are a genetically unique case among mammals because of intensive

selective breeding, which began a few hundred years ago and created

the roughly 400 breeds that exist today.

The first breeds were probably molded for hunting and other work. By

the n era, about 150 years ago, form trumped function.

" Very rich ns wanted these strange dogs as curiosities, to

set them apart from the common man, " said K. Wayne, an

evolutionary biologist at UCLA who contributed to the study.

A breeder who noticed a puppy with short legs, for example, would

cross it with its siblings to fix that trait in a line.

Before writing " On the Origin of Species, " Darwin visited dog

breeders to observe the wide genetic variability among breeds that

can result from selective breeding.

Before such breeding began in earnest, the chromosomes of dogs were

as varied as in other animals.

By mating close relatives to produce animals with specific traits — a

kind of forced evolution — breeders erased much of the genetic

diversity within each breed.

Because so many genes were the same, they passed from generation to

generation in unusually large chunks.

Those chunks, called haplotypes, locked together genes controlling

disparate traits. Thus an entire breed of dogs might inherit, along

with a pure black coat or an acute sense of smell, a particular

disease.

Dogs' unusual genetic architecture has made them valuable for medical

research.

Scientists look for aberrant genes by comparing the DNA of subjects

that either possess or lack a particular trait. Genes contained in

bigger haplotypes are easier to find.

Dogs' haplotypes are 50 times the size of humans', making it more

efficient to hunt for disease-causing genes, the researchers found.

Once a gene is identified in dogs, " it just takes a second " to find

the equivalent gene in humans, Wayne said.

Dogs have already proved useful as proxies for humans in medical

research. The gene that causes the sleeping disorder narcolepsy was

first identified in Doberman pinschers and Labrador retrievers, and

genetic defects associated with epilepsy came to light in studies of

pointers that had the disease.

Beyond the search for diseases, the dog's genetic code contains

glimpses into the unique relationship between humans and dogs.

Since the first wild gray wolves began loitering around human

encampments in East Asia as many as 100,000 years ago, the two

species have been fated to be companions. This long coexistence has

infused dogs with behaviors that are nearly human, as any dog owner

can attest.

At first, the creatures probably kept their distance, coming close

only to eat leftover food.

Over time, humans molded them to fit in with their societies.

Archeological evidence shows that dog domestication was complete by

12,000 to 14,000 years ago, Wayne said. When humans crossed the

Bering Strait land bridge from Asia to North America at the end of

the last ice age, dogs came with them.

More than a decade ago, researchers tried to find the genes linked to

canine behaviors. It was a first step toward untangling the biology

of being.

They didn't have much success. With the dog genome in hand, it's time

to try again, said Elaine A. Ostrander, chief of cancer genetics at

the National Human Genome Research Institute.

" Why do herding dogs herd, and why do pointers point? " she said. " The

research community is really ready to tackle these challenges head-

on. "