A female boxer dog has provided the DNA for the first complete sequence of the dog genome, putting into the doghouse the patchy, 80% coverage of a poodle called Shadow, published two years ago.
A publicly funded consortium led by Kerstin Lindblad-Toh of the Broad Institute, in Cambridge, Massachusetts, US, used the shotgun sequencing technique to map the genome of Tasha, an inbred boxer. With this technique the genome is first broken into fragments and the DNA sequence of each determined. Then a computer stitches the fragments back together.
The process must be repeated several times to ensure accuracy, and the new draft is the product of 7.5 repetitions. The genome of Shadow, the poodle owned by gene-entrepreneur Craig Venter, had only 1.5 times coverage. The boxer was chosen as it is highly inbred. That means the difference between its paired chromosomes are smaller, making sequencing easier.
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Domestic dogs vary wildly in appearance, yet their genomes are 99.85% similar. The boxer and the poodle, for example, differ by about a single nucleotide change in every 900 bases. 鈥淎 dog is a dog in a genomic sense,鈥� says Lindblad-Toh.
Cancer, epilepsy and diabetes
Dogs also have more genes in common with humans than do mice, despite splitting from our common ancestor before mice did. So the more detailed coverage will greatly improve our understanding of the genes underlying appearance and some diseases.
鈥淒ogs and humans share many diseases, including cancer, epilepsy and diabetes,鈥� says co-author Elinor Karlsson, also at the Broad Institute. 鈥淏y directly comparing the disease genes found in dogs to genes in humans, discoveries made in dogs can benefit human medicine.鈥�
As well as Tasha鈥檚 genome, the researchers sequenced smaller parts of the genomes from 10 other dog breeds, such as the German shepherd, beagle and Italian greyhound, as well as closely related species, the grey wolf and the coyote. They catalogued some 2.5 million individual DNA differences between breeds.
The greater than 99% coverage of the 2.4 billion letters of Tasha鈥檚 genome has also revealed an important twist in our understanding of how natural selection works on DNA. Much of the non-coding DNA in dogs is the same as that in humans, indicating that it is under strong natural selection.
鈥淗ence, non-coding DNA is not just 聭junk鈥�,鈥� says Hans Ellegren, of the department of evolutionary biology at Uppsala University, Sweden. Instead, he says that such sequences may constitute non-coding RNA or may have a regulatory function.
Journal reference: Nature (DOI: 10.1038/nature04338)
