The Harry M. Zweig Memorial Fund for Equine Research

Horse Genome Project: Functional Genomics of the Equine Immune System

Dr. Douglas F. Antczak

Objective: The overall objective of this project is to advance knowledge of the equine genome. Specifically, in the coming two years we propose to concentrate our efforts on genes of the immune system of the horse. This focus will support the equine research of several established and new investigators at Cornell, and thus begin to fulfill the promise of practical application that justified the previous awards for the Horse Genome Project from the Zweig Fund.

Background and Significance: The Genome is the collection of all the genes of an organism. The comprehensive study of the Genome, that is, of all of the genetic material of a human, plant, or animal, is called Genomics. The term was coined to distinguish this type of investigation from the more familiar word Genetics, which refers to the study of the inheritance and function of individual genes. The Genome contains biological information - a blueprint or code that the cells of our bodies use to produce proteins and other molecules necessary for life. The information in the Genome is contained in the sequences of the chemical molecule DNA, which itself is packaged in long strands called chromosomes. For mammals, whose DNA contains over 3 billion bits of information and over 30,000 individual genes, studies of the Genome can be a daunting prospect. However, the development of new technologies for gene identification and sequencing has made possible rapid progress in the field of Genomics in a number of species, including the horse.

During the past eight years (1996-2003) Cornell has participated in and become a leading member of the International Horse Genome Project Workshop. This consortium of over 20 laboratories from more than a dozen countries has collaborated to produce the first genetic map of the horse. This map is already being used by equine scientists and there is potential for many more important applications in the future.

Specific Aims for 2004: This application seeks continued support for Phase II of Cornell's participation in the international collaboration of the Horse Genome Project. Specifically, during 2004 - 2005 we propose to work in the following areas:

1) Gene Discovery: Collaborating with other members of the Horse Genome Project, we would continue to , increase the density of the horse gene map through high throughput sequencing and characterization of expressed horse genes contained in two gene libraries produced for us in 2001. It should be possible for the Horse Genome Project scientists to determine sequences from most of the predicted 30,000 equine genes within the next two years, adding to the 14,000+ equine gene sequences already determined. These genes will be used to create so-called gene chip "microarrays" that can be used to assess the activity of thousands of genes in a single experiment. This technology should find wide application in many areas of equine medicine and surgery in the near future.

2) Focus on Genes of the Immune System. We would continue our molecular studies of selected genes of the equine immune system by 'data mining' a new Bacterial Artificial Chromosome library (see progress report below). DNA clones containing the most important genes regulating immunity are being isolated from the library and assigned to horse chromosomes. These genes are also being used for. the production of new antibody reagents that are required for clinical investigations of the immune system by our own laboratory group, and by other investigators at Cornell and elsewhere.

In partnership with the Havemeyer Foundation we have convened a group of veterinary scientists and clinicians from around the world who are committed to advancing practical knowledge of the immune system of the horse through the use of information in the horse genome. This group, known as the Equine Immunology Workshop, has begun to collaborate on projects ranging from defense against infectious diseases to equine allergies.