Because traits and diseases often cluster according to breed and because breeders maintain extensive pedigrees, canine geneticists have long argued that the dog represents an ideal natural model for examining how genes shape appearance, function, behavior and health. In 1991, Jasper Rine, a geneticist at the University of California, Berkeley, with two researchers in his lab—Mark Neff, a postdoctoral fellow, and Elaine Ostrander, a staff scientist—started the Dog Genome Project to study those issues and in the process create a map of the dog genome they could link to that of the human genome for comparative study. [Ed. Note: See interview with Mark Neff.] From that effort was born a cottage industry, under the informal leadership of Dr. Ostrander (now at the National Human Genome Research Institute of the National Institutes of Health) and involving a small group of scientists worldwide, devoted to sequencing the dog genome, segment by segment. The researchers also lobbied to have the dog genome sequenced as part of the continuing Human Genome Project, in order to complete the task quickly and accurately.
In 2003, scientists at the Institute for Genomic Research and what is now the J. Craig Venter Institute in Rockville, Md., published a proprietary sequence covering 75 percent of the genome of a Standard Poodle, Shadow. On the other hand, sequences prepared as part of the Human Genome Project are posted in public data banks in the US, Europe and Japan as soon as possible after they are completed, so researchers can have access to them.
In July 2004, without fanfare, researchers from the Broad Institute at MIT and Harvard and Agencourt Bioscience Corp., of Beverly, Mass., led by Kerstin Lindblad-Toh, deposited in those public data banks their “first draft” sequence of 98 percent of the genetic code for “dog” in general and Tasha, an inbred Boxer from upstate New York, in particular. Their sequence was more complete and considerably more detailed than that of Shadow.
Then came a pause—of the seemingly interminable sort that occurs between the time certain dogs are called while snorfling in the park and the time they decide to respond—that was devoted to revision, analysis and assigning chunks of the sequence to their appropriate chromosome. The dog has 38 pairs of autosomal chromosomes—inheriting one from each parent—and two sex chromosomes. Lindblad-Toh’s team did not sequence the Y (male) chromosome.
Finally, at a press conference in Boston on December 7, 2005; in a lengthy article in the prestigious journal Nature on December 8; and in supplemental articles in the December issue of Genome Research, Lindblad-Toh and her team, along with Ostrander and dog genome scientists, officially unveiled the by then 99 percent complete sequence of Tasha and a SNP (pronounced “snip”) map showing 2.5 million “single nucleotide polymorphisms,” or mutations, in the genomes of Tasha, nine other purebred dogs, four wolves and a coyote. This map is useful for finding genes and examining interrelations between groups and individuals. The Nature article also contained an analysis by Lindblad-Toh’s research team of the dog genome’s structure and a new look at the dog’s family tree, origins and transformation by humans. (Full disclosure: Bark deadlines being what they are, I did not attend the press conference, which was designed to receive maximum coverage in the daily media.)
The Dog Genome
Much of genomic science is still involved with characterization and description of the DNA sequence and parts therein, genes being only the most famous. It involves naming things previously perceived dimly, if at all, and often of unknown purpose. But without that basic work, the genome is basically unreadable.