Whitehead Genome Center Begins Sequencing Dog As Chimp Draft Nears Completion

Sequencing the dog genome will add more power to the rapidly growing scientific effort in comparative genomics, helping us better understand and mine the valuable information in the human genome. To date, scientists have sequenced the human, mouse, rat, worm, fly, and fungi. Scientists will have an initial working draft of the chimpanzee genome (Pan troglodytes) by the end of July.

The dog genome project represents an important addition to the comparative genomics database. For instance, the top 10 diseases among purebred dogs include several that afflict humans, such as cancer, epilepsy, heart disease, allergy, retinal disease and cataracts. Further, the dog has long been studied by pharmaceutical companies and academic institutions as an important physiological model and has aided the development of life-saving, bone marrow transplant techniques.

Tasha the Boxer Dog

"The dog genome sequence will be a powerful basic resource that will rapidly propel the discovery of disease genes forward in both the dog and human,'' says Kerstin Lindblad-Toh, Ph.D., lead researcher for the project at the Whitehead Institute/MIT Center for Genome Research.

The breed of dog to be sequenced is the boxer because it is one of the breeds with the least amount of variation in its genome and therefore is likely to give an easily assembled genome sequence. The Whitehead Genome Center will begin sequencing the genome of Tasha, a female boxer dog, within the next few weeks. Before Tasha was chosen, scientists analyzed more than 60 breeds and 120 dogs. The researchers chose a female because it offers the same representation of X chromosomes as autosomes. The sequencing of Tasha is scheduled for completion by June 2004. Her sequence will then be compared to small amounts of sequence from 10 to 20 other breeds, including the beagle, to study genetic variation within the canine species.

"On behalf of the whole canine genome community, we are incredibly enthusiastic because this will accelerate discovery of genes important in canine health and biology," says Elaine Ostrander, member of the Fred Hutchinson Cancer Research Center and professor at the University of Washington in Seattle.

Many mammals have genomes relatively similar to that of humans. The genome of C. familiaris is an ideal one to study, however, because of the careful selective breeding by dog enthusiasts that has resulted in more than 300 purebreds--offspring resulting from a closed gene pool--during the past 300 years. Within each breed, key traits are inherited generation after generation, including more than 400 inherited disorders. This selective breeding has created tremendous variation among different breeds in terms of height, weight, color and temperament.

The C. familiaris genome is similar in size to that of humans and other mammals, with an estimated 2.8 billion base pairs. The draft sequencing will show the order of the chemical bases A, T, C and G along Tasha's 39 chromosomes. When the researchers have an assembly, they will choose clones from a stretch of sequence (called a supercontig) and those will be mapped to the chromosomes. Then, the scientists will be able to see what the sequence of each chromosome is.

The dog genome will be sequenced using the Whole Genome Shotgun approach, in which the sequence from the entire genome is generated and reassembled by recognizing identical segments using the ARACHNE assembler, developed at the Whitehead/MIT Genome Center. The researchers expect to have 6.5-fold coverage of the genome, which means that the location of every DNA letter will be determined an average of 6.5 times, a frequency that ensures a high degree of accuracy.

Chimp Draft Almost Done

Meanwhile, by next month, researchers at the Whitehead Institute/MIT Center for Genome Research and Washington University School of Medicine will complete the sequencing work necessary (approximately four-fold coverage) to create an initial working draft of the much-anticipated chimpanzee genome. The groups, funded by NHGRI, are now assembling the chimp genome sequence into a working draft using the human genome as a guide. They will then analyze the information and compare it to the human genome sequence.

"The sequence of mammalian genomes, like the dog and chimpanzee, represent very important chapters in evolution's lab notebook," says Dr. Eric Lander, Director of the Whitehead Institute/MIT Center for Genome Research. "Being able to read this notebook and compare genomic information across species allows us to glean important information about ourselves."

The sequencing of the chimp genome began in January 2003. The availability of this genome, which differs from that of humans by only about 1.4 percent, will greatly expand researchers' understanding of human disease, human evolution and genetic selection. Researchers expect to be able to point to which human genes and regions of the human genome are "new," in evolutionary terms, and what genes in each species have been deleted through the many years of evolution.

Of great interest to researchers are a few of the obvious differences between chimps and humans, including our upright vertebral column and differences in disease susceptibility, such as certain malarial infections that humans contract but to which chimps seem to be immune.

The Whitehead Institute/MIT Center for Genome Research is an international leader in the field of genomics, the study of all of the genes in an organism and how they function together in health and human disease. A flagship of the Human Genome Project, the Center today houses a broad range of thriving research programs combining structural genomics, medical and population genetics, and clinical medicine. The Center's annual budget is $80 million, and it employs 350 people, including scientists and medical researchers from Whitehead, MIT, and Harvard.

For more information, contact:
Lisa Marinelli, 617.252.1967