Published online 31 October 2007 | Nature | doi:10.1038/news.2007.208

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Cat joins the genome club

Draft sequence of cat announced.

Cats like the Abyssinian are often studied as a model for blindness.Corbis

A 4-year-old Abyssinian named Cinnamon has become the first cat to have its genome decoded. She joins a menagerie that now includes dogs, mice, rats and chimps. Dozens more animals wait in the genome queue — from armadillos to wallabies.

The sequence is a rough version that includes just 60% of Cinnamon’s total allotment of DNA 'letters' (As, Cs, Ts and Gs) with many holes in between.

But the 'light' treatment, which was done for $10 million, is good enough for some types of studies, the researchers say. The strategy should serve as a model for how to sequence the genomes of other animals that lack a large research community to push for a fuller and costlier genome, says Stephen O’Brien, a geneticist at the National Cancer Institute (NCI) in Frederick, Maryland, who spearheaded the project.

“This is kind of a how-to map of what to do when you sequence an aardvark,” he says.

The sequence should speed up the discovery of genes linked to cat traits and diseases. Earlier this year, with the help of the sequence, O’Brien’s team found a mutation that has left Cinnamon blind since she was a kitten1. It causes a condition, common in Abyssinian cats, called retinitis pigmentosa.

Puzzle pieces

When mapping a genome, researchers shred the long stretch of billions of base pairs (or DNA letters) into shorter segments that are decoded by machines. But it's easy to miss some sections of a genome this way.

To make sure the whole genome gets covered, scientists sequence enough stretches of DNA to add up to many times the total length of a genome. The more such sequencing is done, the fewer letters scientists are likely to miss. With Cinnamon, O’Brien’s team sequenced about 5 billion base pairs — 1.9 times the length of her 2.7 billion base-pair genome. For comparison, the human genome was sequenced seven times over, and the dog’s seven and a half times.

The problem then is putting all the millions of sequenced pieces back together, and in order. This can be done by looking at the overlap between sequenced pieces. But the sparse coverage seen in the cat makes it hard to reassemble.

As a shortcut, O’Brien and NCI bioinformaticist Joan Pontius lined up short stretches of cat DNA against similar sections of the dog and human genomes. That gave them a quicker and better way to fit the DNA together, they report online today in Genome Research2.

Picture imperfect

The result wasn’t a perfect sequence, but it is better than would be expected from such limited sequencing, says O’Brien. “There are going to be some mistakes in there, but probably less than 1% of the time we'll be wrong,” he says.

The team identified more than 20,000 genes and mapped 327,000 single letter differences that occur between cats. Researchers can freely access the information on a website called Garfield .

The sequence will be useful; cats are used as a model to study conditions such as blindness and HIV. "Just yesterday, I pulled a gene off it," says Kathryn Meurs, a veterinarian at Washington State University in Pullman, who studies genes linked to cardiomyopathy, a heart disease that affects cats and humans. A month ago, she says, she would have had to do several weeks of lab work to find a cat equivalent of a human gene of interest — and there was no guarantee that she would find it.

Menagerie

In 2005, the US National Institutes of Health announced plans to sequence 26 mammals, including alpacas, elephants and dolphins, with the same sort of coverage as the cat.

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Those plans are advancing. But others argue that as the price of sequencing comes down, there's no point in only doing a light sequencing. “It’s a little bit like reading a book where you only get to read half of every sentence,” says Steven Salzberg, a computational biologist at the University of Maryland in College Park.

Salzberg supports releasing early drafts of sequences, so long as researchers continue to work towards a better version. He’ll get his wish with Cinnamon’s DNA: a more complete sequence — even better than the dog’s — is due early next year. 

  • References

    1. Menotti-Raymond, M. et al. J. Hered. 98, 211-220 (2007). | Article | PubMed | ChemPort |
    2. Pontius, J. U. et al. Genome Res. 17, 1675-1689 (2007).
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