Genome roundup

Researchers make strides in genome sequencing
Published on February 01, 2004
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This past December, scientists completed a first draft of the genome sequence of the chimpanzee. This ape joins a handful of other animals whose genomes were sequenced in 2003, and several more sequence maps are expected in 2004.

The chimpanzee sequencing was performed at the Washington University School of Medicine and Massachusetts Institute of Technology/Harvard University Eli & Edythe Broad Institute, formerly the Whitehead Institute. The map covers approximately 90 percent of the animal's genome. Since chimpanzees are the species most closely related to humans, scientists are eagerly anticipating the results from a comparative analysis of the two genomes.

The comparison may also fuel a debate. "In terms of research, similarities between humans and chimpanzees have long contributed to both sides of the controversy over their use as research models," said Dr. Taranjit Kaur, university veterinarian and director of laboratory animal resources at Virginia Polytechnic Institute and State University. "This controversy is based on 'reason, emotion, deception, kindness, and political savvy,' characteristics that have been reported in chimpanzees, and also are common in humans."

A growing list
In the past year, much progress has been made in animal genome sequencing. The mouse sequence map was published in December of 2002 and was followed a few months later by a map of the rat. This past fall, scientists at The Institute for Genomic Research and The Center for the Advancement of Genomics released a sequencing map of a dog, a Standard Poodle, covering nearly 80 percent of the canine genome (see JAVMA, Nov. 15, 2003, page 1405).

Other organisms include the pufferfish (Tetraodon nigroviridis), roundworm (Caenorhabditis briggsae), and sea squirt (Ciona savignyi), with the honeybee (Apis mellifera) joining this group a month ago, in January. At press time, the National Human Genome Research Institute said to expect a draft of the chicken sequence any month now.

The NHGRI, a division of the National Institutes of Health, provided substantial funding for these sequencing projects, except for the Poodle. Government agencies such as the Department of Agriculture, and other organizations and companies, also provided funding. And, in many cases, mapping projects involve international collaborations.

It is also important to note that most genome sequencing efforts rely on previous work by other scientists, such as the development of bacterial artificial chromosome libraries and availability of consensus genetic linkage maps.

For example, a number of research groups around the world have been identifying equine genes and markers since the mid 1990s, and this research will be used, whenever enough money can be raised for a sequencing project. Recently, Ohio State University announced they had created the first equine gene chip that contains more than 3,200 expressed horse genes. Other projects are just beginning. This past fall, researchers from the Nicholas Turkey Breeding Farms in California, University of Minnesota in St. Paul, and University of Kentucky in Lexington announced they had mapped roughly 100 genes in the turkey genome.

After a draft is released, subsequent drafts will further refine the sequence and fill in the gaps. Then, researchers return to the task of identifying the genes within the code.

Benefits for animals and humans
Scientists are excited about the progress being made. Some are most interested from a comparative genomic standpoint and human health perspective. "Comparing the human genome sequence with those of other organisms helps us to identify regions of similarity and difference, providing critical clues about the structure and function of human genes," said Francis S. Collins, MD, PhD, NHGRI's director. "This information should point us toward better strategies for treating and preventing human disease. With each genome that we sequence, this approach becomes more powerful."

Other researchers are intrigued by the potential benefits for animal health. Dogs and humans, for example, are prone to many of the same diseases: cancer, heart disease, and autoimmune disorders. Research on the genetics of these diseases may yield new techniques to combat these diseases in dogs as well as humans, according to Dr. Collins.

"I think sequencing is the first step to identifying target genes and the regulation of those genes at a species level," said Dr. Muquarrab Qureshi, program leader for the National Animal Genome Research Program at the USDA Cooperative State Research, Education, and Extension Service. He says if you have identified a region on the genome known to be involved in improving the performance characteristics of an animal, commonly described as a quantitative trait loci, you may want to select animals for those markers. "The gene sequence information will really help us to decide what are the target genes of both economic and health importance," he commented.

Robin Morgan, PhD, a poultry expert and dean of the University of Delaware's College of Agriculture and Natural Resources, has a similar outlook on the chicken genome map. "The chicken genome sequence will have enormous impact on the poultry industry," she said. "In addition to facilitating basic research on chickens, in time, sequence information will be supplied toward the identification of genes that can be exploited to improve disease resistance, other production traits, and feed efficiency/nutrient utilization."

Future maps
In the next year, we can expect the release of additional genome-sequencing maps. The chicken map is expected any day. Another canine map, this time of a Boxer, and funded primarily through NHGRI, is expected in March or April. The Baylor College of Medicine will start sequencing the genome of the rhesus macaque, and the Broad Institute will sequence the opossum.

In December, Agriculture Secretary Ann M. Veneman also announced the launch of a $53 million bovine genome-sequencing project, a collaborative effort among NHGRI, USDA, the state of Texas, the Commonwealth Scientific and Industrial Research Organization of Australia, and two New Zealand companies—Agritech Investments Ltd, and Dairy Insight Inc.

Dr. Qureshi says that the Swine Genome Sequencing Consortium, a group involving a number of U.S. and international academicians, stakeholders, and companies, is planning to start sequencing the swine genome. Swine industry and interest groups have dubbed this sequencing a priority. Dr. Qureshi says the consortium is working with the federal, state, industry, and international partners to identify the sources and acquire the level of funding needed for the project.

In the meantime, researchers from around the world will continue to lay the foundation for other genome maps, including those for the horse, cat, sheep, deer, salmon, and turkey—and the list goes on. "There is a lot of preliminary effort underway in defining the infrastructure and the genome landscape," Dr. Qureshi said. "Depending upon budget availability, other species will also move along (to be sequenced)."