In Dog Genome, Scientists See Man's Best Hope

[Guest guest]

By Brown

There probably isn't a tail-wagging gene or a face-licking gene. But there

undoubtedly are groups of genes that explain why retrievers chase sticks,

spaniels jump in the water at every opportunity, and border collies like to

herd sheep and small children.

The biological basis of the astonishing variety of behaviors of man's best

friend is a big step closer to comprehension today with the publication of

the dog's genome -- its 2.41 billion nucleotides, or DNA " letters. "

The dog -- in the form of a female boxer named Tasha -- joins the human, the

chimpanzee, the mouse and the rat on the list of mammals whose genetic

instruction manual has been transcribed. The genomes of the fruit fly, a

microscopic worm, yeast and several bacteria have also been decoded.

But the dog genome is far more than a curiosity. It is already providing

insights into evolution and will probably make dogs the chief tool for

understanding the genetic diseases of people.

Certain breeds are at much higher risk than others for specific ailments.

Samoyeds have a tendency to become diabetic, Rottweilers develop the bone

cancer osteosarcoma, springer spaniels are at risk for epilepsy, and

Doberman pinschers suffer from narcolepsy much more often than other

canines. All these diseases have human counterparts.

" This offers a strategy for tracking down the location of genes involved in

medical conditions that in the past we have just not been able to tackle, "

said Francis S. , director of the National Human Genome Research

Institute, which helped pay for the work.

S. Lander, director of the Broad Institute in Cambridge, Mass., where

the research was done, said: " The genetic structure of dog breeds is so much

clearer than in the human population that it will make genetic analysis much

simpler. "

The work is the product of nearly 250 scientists organized through the

institute, which is affiliated with Harvard and the Massachusetts Institute

of Technology. A much less detailed version of the dog genome by a different

research group was published two years ago.

In size, appearance and behavior, the dog is the most diverse species on

Earth. It was the first animal domesticated from the wild, at least 15,000

years ago. Its many subspecies, or breeds, were sculpted by man, so it's no

surprise that man should want to shine the illuminating light of genome

science on his longtime companion.

A genome is the total mass of genetic instruction an organism inherits. It

consists of strings of DNA nucleotides, the biological equivalent of

letters. The instructions on how to build a body -- including permanent

structures such as teeth and brain cells as well as short-lived substances

such as blood and hormones -- are contained in the order of the nucleotide

" letters " on the strings. Humans have about 3 billion nucleotides in their

genome.

Stretches of hundreds or thousands of nucleotides are copied inside cells

and direct them to produce specific proteins, the building blocks of

organisms. These stretches are called genes.

Humans have about 22,000 genes. Dogs, according to the new research, have

about 19,300. A given gene usually comes in slightly different variations,

similar to pencils with different colored lead, or scissors of varying size

and shape.

All dogs are descended from gray wolves, which were originally domesticated

in East Asia. Some breeds, such as the Akita, have existed for more than

1,000 years. Most, though, are the product of selective breeding in the past

400 years to create specific characteristics.

That breeding has, in effect, concentrated specific versions of specific

genes in specific populations of dogs. The result is a breed with physical

and behavioral traits that existed in ancestral dogs but are now greatly

magnified.

This results in animals that can look and act very different even though

they scarcely differ from one another in their genetic identity. On a

genetic level, breeds differ from one another only about as much as humans

do. Gray wolves have more in common with Mexican hairless Chihuahuas than

with coyotes, which they more closely resemble.

As traits have coalesced in breeds, so have specific diseases. That happened

because genes involved in the diseases are physical neighbors of the trait

genes; they move together in long stretches of DNA called haplotype blocks.

The blocks are 50 times as long in dogs as in people. This is because most

breeds are only 30 to 90 generations old, much younger than human

populations.

By studying the genomes of dogs of the same breed that have the same disease

-- for example, a group of German shepherds with kidney cancer -- scientists

can identify the genes responsible. Because the blocks are so large,

researchers can narrow the possible location of disease genes to a few

" neighborhoods " in the genome. They can then search in those stretches of

DNA for the culprit genes.

" Breed-creation gives us a genome structure that makes it very easy to find

disease genes, " said Kerstin Lindblad-Toh, the lead author of the paper,

which appears in the journal Nature. " We now have the tools; we have

actually started cancer studies. "

Similarly, scientists may be able to figure out what genes contribute to

complex behaviors such as retrieving and pointing. They will look for

haplotype blocks shared by different breeds with the same trait -- all

retrievers or all pointers -- but that aren't found in breeds lacking the

trait.

That work will be harder, Lindblad-Toh said. Nevertheless, it may provide

insights into behavioral genetics, which historically have been the murkiest

and most controversial part of the field.

Other less practical but equally interesting insights are already arising

from the dog genome.

As with human DNA, only about 5 percent of dog DNA carries genetic

information. The function, if any, of the rest (often termed " junk DNA " ) is

unknown.

The exact number of genes in people, chimpanzees, mice, rats and dogs is

uncertain, but it is now clear that of the 5 percent of genetic information

in the genome, less than half that represents " classical " genes that encode

the instructions to make proteins. The rest is DNA that regulates the

activity of those genes.

The dog researchers identified 0.2 percent of the genome that comprises

" highly conserved " DNA -- the stretches that are essentially identical in

all individuals and across species -- but that do not code for proteins.

They found that half of this favored DNA resides in the neighborhood of only

200 genes, some of which are involved in embryonic development and nerve

growth. It appears to be crucial in the regulation of those genes.

" Which is to say, those genes must be very special. You just don't want to

mess with them, " said. " This will undoubtedly cause other

investigators to look at those 200 genes and ask why they are so important. "