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OLD _NRSP008: National Animal Genome Research Program

Statement of Issues and Justification

Prerequisite Criteria: Mission

The fundamental basis for all of animal breeding and the continuing genetic improvement of all agricultural animal species exists within the genome. At the beginning of the 21st century, it appears likely that at least draft sequences of the genomes of most major animal agriculture species will soon be available. The primary issue becomes how to translate the sequences and related genome-based information into the genetic enhancement of agricultural animal productivity. As the Human Genome Project (HGP) has clearly demonstrated, success in this endeavor requires global coordination of shared resources and shared information. NRSP-8 proposes to continue to provide this for the animal agriculture research community across species boundaries.

Though far from being either complete or totally accurate, the publication of the draft human genome sequence (International Human Genome Sequencing Consortium, 2001; Venter et al., 2001) is a watershed event for modern biology. Developments here and abroad make it likely that similar draft sequences will be generated over the next five years for several agricultural animals, at least for chicken, cattle and swine. At this moment, full sequencing of the chicken and cow genomes has been made a high priority of the NIH National Human Genome Research Institute (see http://www.genome.gov/page.cfm?pageID=10002154). Pig genome sequencing projects are active or under consideration in, at least, Denmark, China and the U.S. Thus, in the near future, animal scientists and veterinarians will be in much the same position as human geneticists and medical doctors are today. The genome sequence exists and is publicly accessible, but how does one extract useful information from it, check that information for accuracy, and apply the information to real-life problems? Moreover, just as for the human sequence, almost all of this sequence will be generated in central genome sequencing centers that have considerable financial and infrastructure support. How will individual or small groups of animal scientists access the tools and technologies without an equivalent support base? These are the critical issues NRSP-8 seeks to address.

Worldwide demand for high quality animal protein continues to grow at an explosive pace. A recent study (Rosegrant et al., 2001; see also Delgado et al., 1999) estimates that world demand for meat will increase by over 50% between 1997 and 2020 and will nearly double in developing countries in that time frame. Almost all of that increase will come in poultry, pork and beef consumption. Meeting that increased demand will depend heavily on continued genetic improvement of these species. NRSP-8 is focused on application of new genomics technology to solving this critical problem. As noted in the FAIR 2002 report, "The field of animal genomics holds great promise for improving animal and human health, food safety, and animal production." (Sigurdson et al., 1999)

Research supported by NRSP-8 is directly relevant to all of the priority objectives under the crosscutting research area of "Genetic Resources Development and Manipulation" set by North Central Region Directors in their research prioritization process. In particular, NRSP-8 supports the top two priorities to "develop new genotypes . . ." and "broaden and enrich the knowledge base about genome makeup and characterization."

Animal breeders and geneticists recognized the potential applications of genomics to their research many years ago but have been limited by the high initial cost of developing high throughput genomics labs and, in some cases, by economic and biological constraints on generating experimental populations. The potential for agricultural genomics was first officially recognized in the 1990 Farm Bill that authorized the USDA National Genetics Resources Program. In order to stimulate cost-effective animal genomics research and to provide opportunities for widespread participation, NRSP-8 was initiated in 1993 and received renewed support in 1998. This has provided the key mechanism that coordinates US genome mapping efforts in cattle, sheep, swine, and poultry; a horse project was added in 1997, and aquaculture species will be added in this renewal. The overall NRSP-8 Technical Committee was subdivided into Species Genome Committees and funding was provided through Species Coordinators to facilitate the exchange of shared materials, maintain genome maps (both physical and genetic), establish databases for sharing information, and provide leadership in establishing research priorities.

To identify, map, and characterize genes involved in economic traits of livestock, advances in agricultural genomics must continue. The current focus of modern biology is "functional genomics", i.e., connecting our rapidly growing knowledge of DNA sequence information to its specific role in the function of the organism. In agriculture, this translates into connecting (and understanding) inherited genetic traits of farm animals (usually called quantitative trait loci, QTL, or economic trait loci, ETL) to the important animal growth and health phenotypes they control. Once functional genomics elucidates the molecular mechanisms underlying these QTL, various methods to improve animal productivity (and health and well-being) logically can be explored (through breeding, nutrition, veterinary, and husbandry practices).

At the moment, most of the species of interest to NRSP-8 possess moderate quality genetic linkage maps (~2-3 cM resolution on average), developed, in part, through previous NRSP-8 collaborations (e.g., Band et al., 2000; Groenen et al., 2000; Maddox et al., 2001; Rohrer et al., 1996). In all cases, these maps are now being maintained on websites (e.g., Hu et al., 2001) that are now being continuously updated, again, often with NRSP-8 support. The maps are being used widely in industry and academia to locate QTL within the genomes in question.

The major priority now is to link these genetic marker maps, that are being used for QTL mapping, directly to the genome sequence data we soon expect to have. This first requires the development of maps based on overlapping sets ("contigs") of large insert ("bacterial artificial chromosome" or BAC) clones, something that's already well underway for many NRSP-8 species (e.g., Vaiman et al., 1999; Eggen et al., 2001; Fahrenkrug et al., 2001; Crooijmans et al., 2000). Second, the BAC contigs must be linked to the specific markers on the existing genetic maps, and they must be assembled into larger contigs that provide high quality genome coverage. Third, both contigs and markers must be aligned with the human and mouse genome sequences already available ("comparative mapping"), so that animal agriculture benefits from the extensive genome research in these species (see Band et al., 2000; Burt et al., 1999; Suchyta et al., 2001; and McCoard et al., 2002 for recent examples). Fourth, so-called "transcriptional profiling" (or "gene chip") technologies must be available to determine which of the ~40,000 genes in each species function in what tissues, at what time in development, and in response to what environmental changes (e.g., Band et al., 2002; Coussens et al., 2002; Liu et al., 2001). Finally, this vast body of information must be subject to careful quality control, must be integrated and must be made available to the user community (the realm of "bioinformatics").

NRSP-8 seeks continued support for its efforts to promote initiatives in agricultural animal genomics such as those described in the preceding paragraph. Individual scientists lack the resources to access these modern technologies on their own and to address critical problems with global approaches that can involve tens of thousands of genes at once. To date, we have kept pace only by collaboration and sharing resources in common. To promote and facilitate such an approach is exactly what the National Animal Genome Research Program was designed to do. Our past success has been amply demonstrated in terms of genetic maps, databases, BAC libraries and filter arrays, DNA and microsatellite marker panels, and joint publications. The future of animal genomics is even more challenging, but even more exciting as we begin to unravel the true genetic foundation that underpins all of animal productivity and health.

This proposed renewal of NRSP-8 is designed to support and complement the activities of several Multistate Research (MR) projects. NRSP-8 focuses on cross-species common maps and/or sequences and providing adequate infrastructure for bioinformatic and genomics research on agricultural animals. Related MR projects primarily focus on species-specific objectives and depend on the resource and infrastructure support of NRSP-8. These MR projects are as follows. NC-168: Advanced Technologies for the Genetic Improvement of Poultry is approved until 9/30/03. The focus of NC-168 is on QTL analysis, transgenic technology, and quantitative genetic theory related to poultry. NC-1004: Genetic and Functional Genomic Approaches to Improve Production and Quality of Pork is a new project with a start date of 10/02. Its objectives are to further understand the dynamic genetic mechanisms that influence production efficiency and quality of pork and to discover genetic mechanisms controlling animal health in pork production. NC-1010: Interpreting Cattle Genomics Data: Biology, Applications and Outreach is a new project with a start date of 10/02. The focus of NC-1010 is to harvest the value of cattle genomics by linking chromosomal DNA information to expression profiles, phenotypes and functions of specific genes and proteins in relevant models of animal husbandry. NCR-204: The Interface of Molecular and Quantitative Genetics in Plant and Animal Breeding is a new project with a start date of 10/02. The focus of NCR-204 is on applications of statistical methodology and computer modeling to breeding programs in both plants and animals. NE-60: Genetic Basis for Resistance and Immunity to Avian Diseases is approved until 9/30/03. NE-60 focuses on the function of genes involved in the immune response in poultry. NE-186: Genetic Maps of Aquaculture Species is approved until 10/02. Its goal is to develop genetic linkage maps, map QTL, and initiate comparative genome mapping for five aquaculture species (catfish, salmonid, tilapia, shrimp, and oyster). S-277: Breeding to Optimize Maternal Performance and Reproduction of Beef Cows in the Southern Region is approved until 10/03. This project is primarily focused on the development and evaluation of subtropically adapted cattle. S-284: Genetic Enhancement of Health and Survival for Dairy Cattle is approved until 10/02. Its focus is primarily on immune function, disease resistance, and reproductive genetics in dairy cattle. WCC-001: Beef Cattle Breeding in the Western Region is approved until 9/30/02. This project focuses on providing information and education materials to improve breeding strategies for beef cattle. All these MR projects, except NCR-204, focus on individual species or species groups. NCR-204 and NRSP-8 are complementary in that the former provides the theoretical base and the latter the resource and information base needed to apply genomics technologies to animal agriculture.

Prerequisite Criteria: How does this NRSP pertain as a national issue?

Rationale: Priority Established by ESCOP/ESS

Rationale: Relevance to stakeholders