Meeting Addresses Prioritization of DNA Genome Sequencing in Animals

In October 2002, a meeting of the Interagency Working Group for domestic animal genome sequencing was convened at the USDA Whitten Building in Washington, D.C. to discuss prioritization of domestic animal species for DNA genome sequencing. That such a meeting might take place was unthinkable only five or six years ago and reflects the dramatic accomplishments that recently resulted in the completion of the DNA sequence of each of the 23 human chromosomes.
The touchstone for this story occurred in February of 2000, when the highly respected scientific journals Nature and Science simultaneously announced the completion of the sequencing of the entire 3 billion letters of DNA that is the genetic blueprint for humans. In scope, complexity and expense, the accomplishment of the Human Genome Project has been likened to NASA’s landing of a man on the moon. And like the lunar landing, the scientific knowledge gained from the Human Genome Project will have innumerable spinoffs that will change our concepts of biology and have profound implications for management of domestic animals.

The Human Genome Project had its inception in 1986 in the form of a draft proposal circulated for comment among a select group of scientists and work was formally started in 1990. The estimated cost of the project was 5 billion dollars and estimated time to completion was 15 years. That the project was completed five years ahead of schedule and approximately one billion dollars under budget reflects the spectacular advances made in DNA sequencing technology, automation, robotics, and computer software development. Almost from its inception, the Human Genome Project benefited from significant advancements in technology and information management so that large-scale DNA sequencing projects in 2002 bear little resemblance to the processes used in 1990. Hand in hand with technological advancements and automation came a dramatic decrease in the time and cost of DNA sequencing. The estimated time for one of the genome sequencing centers (there are three centers in the U.S.) to sequence a mammalian genome in 2003 will be about one year at a cost less than 1% of the cost of sequencing in 1990.

The efficiency and economy of modern DNA sequencing prompted the scientific community to propose the sequencing of numerous other species under the National Human Genome Research Institute's "Model Organisms" program. Selected organisms must provide relevant biological information for human biomedical research and be supported by a research community sufficient to manage and utilize the vast amount of DNA sequence information. Key research species (fruit fly, mouse, and rat) and many important species of bacteria, fungi, and viruses were selected in the early stages and DNA sequences of these genomes have been or will soon be completed.

The Model Organisms program has been expanded to include other species, including animals of significant economic importance; hence the meeting of the Interagency Working Group in Washington last month. Representatives from each of the sequencing centers, from federal agencies that support genome sequencing (NIH, DOE, NSF, OTA, USDA) and about 25 individuals from universities, government laboratories, and the private sector were present. Spirited discussions centered on the scientific necessity for additional genome sequencing and prioritization of species of domestic animals to be selected for DNA sequencing. Several species (cow, dog, and honey bee) appeared to have an inside tract to genome sequencing through preliminary proposals submitted as white papers to the scientific advisory board of the National Human Genome Research Institute. Proponents of swine, cats, and poultry were expected to submit white papers this fall.

Where does this leave the horse? Representatives of the horse research community have been active participants in the genome meetings and sequencing of the horse genome has significant biological merit.
The domestic horse is representative of a major lineage of mammals called the Perissodactyls and is a model for many human genetic disorders. Unfortunately, the formal genetics of the horse lags behind that of all other domestic animals and presents a significant obstacle to sequencing the horse genome. The initial equine gene-mapping workshop was held in Lexington, Ky. in 1995, at least 20 years after similar meetings for cattle, pigs, and poultry. Even so, about 100 researchers from around the world regularly participate in the equine gene mapping workshops under the sponsorship of the Dorothy L. Havemeyer Foundation and the horse enjoys standing committee status in the USDA NRSP8 Animal Genomics. Rapid developments in high density gene mapping, construction of equine DNA libraries, and identification of functional genes are quickly moving knowledge of the horse genome forward and one can reasonably argue that horse genomics in 2002 is where cattle or pig genomics was just four or five years ago.

One might ask what would be the benefits of having the complete DNA sequence for the horse or question whether those benefits would justify the considerable effort and expense of genome sequencing. These are not easy questions to answer, but if the Human Genome Project can serve as an example, we can anticipate the following: Unquestionably there will be many scientific surprises. Having access to the entire DNA sequence of an organism is somewhat like entering a library full of books that no one has ever read. Many biological “truths” will be rigorously evaluated and at least some will be discarded or significantly revised. Research ideas will be formed to address questions that we were previously unable to contemplate. We can anticipate expanding our basic knowledge of what make a horse so similar yet so different from a human or a cow, and we will begin to develop husbandry practices that are specifically tailored to the genetic uniqueness of individual animals. We can anticipate the development of improved DNA-based diagnostic tests to identify animals carrying genetic disorders or predisposed to mechanical injury, infectious disease, reproductive failures, etc. Synthetic vaccines and drugs will be tailored for animals of different genotypes for higher efficiency without the risk of adverse reaction. An easier question to answer is what would be the risk if we did not sequence the horse genome? Not having access to the DNA sequence of the horse would severely limit the quality and depth of future equine research and insure that horses and horse owners would not fully benefit from the rich diversity of knowledge and applications that are coming from contemporary molecular biology and biotechnology.

About the Author

Loren Skow, PhD

Loren Skow, PhD, is a professor in the Department of Veterinary Integrative Biosciences in the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University. His research involves molecular genetic techniques and comparative genomics of hoofed mammals, especially genes involved in immunity and susceptibility to infectious diseases.

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