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Genome will unravel cat mysteries

The New York Times
Published on: 02/15/05
Genetically speaking, every dog has already had its day. In 2003, a
standard poodle named Shadow became the first canine to have his genome
mapped, and in 2004 a boxer, Tasha, became the second.

Now scientists are turning their attention to the genome of the
domestic cat, and it is Cinnamon's turn to donate a blood sample.

Cinnamon is not just any cat. She comes from a carefully bred colony at
the University of Missouri, and her lineage can be traced back for
decades.

Scientists therefore know exactly what they are getting when they look
at her DNA.

Researchers hope to have the cat genome mapped by the end of the year
- perhaps as soon as this summer - and when the job is done, humans
will be the ones to benefit.

Americans own (or serve) more than 60 million cats, spend more than $4
billion a year on cat food and are so dedicated to feline health care
that their veterinarians have identified more than 250 genetic diseases
and hundreds of infectious agents that afflict them.

But the genome will usher in a world of knowledge with immediate
practical application, not only for veterinarians and cat owners, but
for geneticists, zoologists and conservationists as well.

When the National Human Genome Research Institute, part of the National
Institutes of Health, chose the cat as one of the select group of
species to have their genomes mapped, it conferred no small honor. It
will cost $5.5 million to do the job, said a spokesman for the health
institutes, and though the project will produce a map that is far less
detailed than that of the human genome, scientists firmly believe it is
worth every penny.

The sequencing is being carried out under contract with Agencourt
Bioscience Corp., a biotechnology firm in Beverly, Mass., which was
started five years ago by scientists originally involved in the Human
Genome Project.

The cat genome is large, and even though automated equipment is used at
every step, sequencing it is labor intensive; more than 100 people are
involved in one way or another in the project.

The raw material - Cinnamon's DNA - is delivered to Agencourt by
the NIH. Then the work begins, essentially a process of chopping up the
DNA into tiny usable pieces in a process called library construction,
and then putting it all back together to create the map. Producing a
usable first draft sequence takes about nine months.

The Cat Genome Project was announced along with plans to sequence the
genomes of eight other mammals: the elephant, the orangutan, the shrew,
the hedgehog, the guinea pig, the tenrec, the armadillo and the rabbit.

Each new genome map adds something to the understanding of the human
genome, but the cat was chosen, among other reasons, for its importance
as a medical model in studying human disease.

"The genes on the cat chromosome and the human chromosome correspond to
each other like two strings of beads made of different colors," said
Dr. Stephen J. O'Brien, chief of the Laboratory of Genomic Diversity of
the National Cancer Institute, adding that cats have "the same genes,
one after another, strung together across every chromosome."

This resemblance means that many of the cat's genetic diseases are
inherited exactly the same way as genetic illnesses in humans.
Diabetes, hemophilia and lupus, for example, have precise genetic
homologues in cats.

Cat retroviruses, like those that cause feline leukemia and feline
sarcoma, although slightly different in their gene structure from the
human versions, produce lesions that look almost identical to human
cancers. Perhaps even more significant, feline immunodeficiency virus,
or FIV, resembles HIV so closely that it follows the same progression
that, untreated, leads to the wasting syndrome of AIDS in humans. It is
the only known naturally occurring AIDS syndrome in any nonhuman
species, and provides a perfect model for studying the progression of
the disease.

Cats also get feline versions of many other human infectious diseases,
including rotavirus, poxvirus, herpes, Q-fever, chlamydiosis and dozens
more. On top of that, they are resistant to anthrax infection, a fact
of considerable interest to scientists. Once the genome is mapped, said
O'Brien, "research on feline stem cells will blossom, along with gene
therapy applications."

Zoologists and wildlife managers are just as eager as medical
researchers to start using the completed cat genome.

The domestic cat is the only one of the 37 species in its family that
is not either threatened or endangered. Yet despite their rapidly
shrinking territory, and their limited genetic diversity within
species, wild cats endure on every continent except Australia and
Antarctica, at the top of the food chain wherever they live.

"The free-ranging species are survivors," O'Brien said. "Cheetahs, for
example, get infected with FIV, but they don't get sick," though no one
knows why.

On the other hand, wild cats can become infected for reasons that are
just as mysterious. This happened in 1994 when the canine distemper
virus, which normally infects only dogs, suddenly jumped to lions.
Wildlife managers watched, appalled, as the virus swept through the
population, killing one-third of the lions in the Serengeti ecosystem
in only nine months.

Zoologists want to know what explains these evolved genetic defenses
and susceptibilities. The genomes of the domestic cat and its wild
relatives are almost identical, and the genetic information developed
for the domestic cat will apply widely to all the species in its genus.

"The full genome," O'Brien said, "will empower people with tools to
discover innate disease defenses, recognize pathogens and other threats
and assess the present status and future of these species."

Cats were probably first domesticated about 6,000 years ago, making
them much newer guests in the human household than dogs or barnyard
animals, which have lived with humans for almost twice as long. Yet
they are the domestic animal closest to our hearts in more ways than
one.

"At least from a genomic perspective," O'Brien said, "cats share a
striking ancient affinity with humankind."