Studying The Dog DNA Sequence

Letting the Dog Genome Out: Poodle DNA compared
with that of mice, people
John Travis


Chihuahuas, Irish wolfhounds, pit bulls, beagles, greyhounds, and
more. Man's best friend comes in a range of sizes, shapes, and
temperaments unmatched by any other mammalian species. Biologists
have now taken a step toward understanding that diversity by
conducting a limited, but relatively quick and inexpensive, scan
of one dog's full DNA sequence, or genome.

The data from this scan should ultimately help researchers study
the more-than-300 human diseases, such as cancer and epilepsy,
that also afflict dogs. The new work has already enabled
scientists to compare the mouse, dog, and human genomes.

"The sequence of our genome is more similar to the dog's, despite
the fact that the dog lineage split off first from the common
ancestor" of all three mammals, says Ewen F. Kirkness of The
Institute for Genomic Research (TIGR) in Rockville, Md., who led
the dog-genome project. The rodent's unusually high mutation rate
has made its DNA diverge more from people's than the dog's DNA
has, he explains.

In the strategy pursued by Kirkness' team, biologists isolate
copies of an animal's genome and break the strands of DNA into
millions of short fragments. After determining the sequence of
nucleotides making up each such piece of DNA, biologists use a
computer to match overlapping sequences and piece together as
much of the animal's full DNA sequence as possible. The more DNA
analyzed, the better the chance that the final genome sequence
will be accurate and have few gaps. For the human and mouse
genomes, geneticists sequenced fragments equaling 6 to 10 times
the DNA in the actual genome of each.

The National Institutes of Health in Bethesda, Md., is sponsoring
a similarly thorough dog-genome project, but Kirkness and his
colleagues wondered whether they could glean important
information from a substantially smaller amount of DNA. If so,
researchers might then consider sequencing the genomes of one
animal from each of the 18 orders of mammals.

In the Sept. 26 Science, Kirkness and his colleagues describe
their survey of the dog genome. They ultimately sequenced DNA
equal to only 1.5 times the genome. From that work, they
determined 77 percent of the dog genome and found canine DNA
fragments corresponding to 18,473 of the 24,567 previously
documented human genes. "We got more than we expected," says
Kirkness.

The newly available dog genome is "just a wonderful resource,"
says Gustavo D. Aguirre of Cornell University.

The canine DNA analyzed came from a male standard poodle
belonging to two of the coauthors on the new report, TIGR's
Claire M. Fraser and J. Craig Venter of The Center for
Advancement of Genomics, also in Rockville. That selection isn't
surprising given that Venter used his own DNA when his former
company, Celera, performed its commercial sequencing of the human
genome (SN: 5/23/98, p. 334). NIH's dog-genome project, scheduled
to finish next year, uses DNA from a boxer.

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