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 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.

Objectives:

1. Enhance and integrate genetic and physical maps of agriculturally important animals for cross species comparisons and sequence annotation.
2. Facilitate integration of genomic, transcriptional, proteomic and metabolomic approaches toward better understanding of biological mechanisms underlying economically important traits.
3. Facilitate and implement bioinformatic tools to extract, analyze, store and disseminate information. (See Attachment 1 for more details on objectives.)

• Enhancement of scientific knowledge and genetic improvement of U.S. livestock, poultry and aquatic breeding through increased knowledge of genome organization and gene function, and improved breeding and management strategies.
• Coordination of research and extension programs to enhance animal genomics research and applications through development of shared databases, development of shared experimental tools, and enhanced communication and collaboration.
• Promotion of a competitive advantage to U.S. agriculture through increased support of research by agricultural industries and by advancing discoveries through technology transfer.

The NRSP-8 Committee has developed and utilized a number of communication mechanisms and these will continue to be developed and improved upon through this renewal project. Databases have been developed in collaboration with international colleagues for cattle, horses, poultry, sheep and swine and these databases are easily accessed via web sites that have been developed for each species (see Past Accomplishments in Attachment 2). Some of these sites also include information about animal genomics for lay audiences. The NAGRP (NRSP-8) web server based at Iowa State University (http://www.genome.iastate.edu/) receives over 120,000 requests each month from more than 9,000 users worldwide. These efforts have contributed to the successful white paper submissions to the NIH in support of making sequencing of the chicken and cattle genomes a high priority. These databases and web sites will be updated and improved, and similar resources will be developed for aquaculture species as part of this renewal.

The Animal Gene Mapping Community Directory (http://www.genome.iastate.edu/community/angenmap/dir.php) was established in 1999. It currently includes 474 individual entries and it continues to grow. The ANGENMAP discussion list (ANGENMAP@iastate.edu) currently has 880 subscribers from over 40 countries and the number of subscribers has been increasing by about 15% each year. Approximately 400 e-mails are posted to this list annually and the number increases by about 25% each year. This demonstrates that animal genome scientists are eager to share questions and information and the ANGENMAP discussion list has been a very effective communication mechanism. Many NRSP-8 participants are active members of the International Society for Animal Genetics and they participate in various international meetings including the International Conference on Animal Genetics and the World Congress on Genetics Applied to Livestock Production. In addition, the NRSP-8 committee officers represent the animal species on the Plant and Animal Genome Conference organizing committee. The NRSP-8 committee sponsors workshops for each of the species at the annual PAG Conference. There are typically well over 100 attendees at each of these workshops and they provide an excellent forum for networking among animal genome scientists and also for recruiting new participants. NRSP-8 scientists have forged numerous linkages with scientists working in other disciplines and in industry (see Additional Linkages in Attachment 3). These linkages will continue to be developed and strengthened by the renewal project.

The NRSP-8 Species Coordinators and other members of the Technical Committee give numerous presentations to industry groups such as the Poultry Breeders. Roundtable and other lay audiences. An average of 3-5 such presentations are given by each Coordinator each year. In addition, the Coordinators are frequently contacted for media interviews and they respond to dozens of e-mails each year from lay individuals including youth. Two newsletters, Pig Genome Update (6 issues per year) and Poultry Genome Newsletter (4 issues per year), are distributed to scientists and industry personnel. These newsletters are each sent to several hundred recipients and they are also posted to the ANGENMAP discussion list. Thus, information about progress in animal genome research is distributed to over 1,000 individuals through these newsletters.

One goal of the proposed NRSP-8 renewal project is to enhance scientific knowledge and genetic improvement of U.S. livestock, poultry and aquatic species. This will be accomplished by increasing knowledge of genomics and gene function, applying genomic research to improve production of food and animal products, and educating scientists, agricultural producers and consumers about the safe use of genomics to improve food production. A second goal is to coordinate research and extension programs to enhance animal genomics research and applications. This will be accomplished through development of shared database tools and databases, development of shared experimental resources and access to unpublished data to improve and enhance discovery, creation of comparative genome maps, and coordination of shared publications, workshops and information packets for scientists, producers and consumers. A third goal is to promote competitive advantage to U.S. agriculture. This will be accomplished by encouraging increased support of research by agricultural industries and advancing discoveries through technology transfer.

Governance:
The NRSP-8 Technical Committee is composed of participating scientists appointed by SAES Directors or other administrators of each cooperating organization. The Technical Committee annually elects a Chair-elect/Secretary, who then becomes Chair the following year and Past-Chair in the third year. These three officers along with one of the Coordinators (see below) represent the animal species on the organizing committee for the annual Plant and Animal Genome Conference. Members of the Technical Committee make up Species Sub-committees that work with the designated Species Coordinators and the Database Coordinator to develop priorities for each species. The Technical Committee prepares an annual progress report that reviews project accomplishments, including publications associated with the project, and outlines future plans. The Executive Committee deals with activities between scheduled meetings of the full Technical Committee and is composed of the Technical Committee Chairperson and Chair-elect/Secretary, Species Sub-committee Chairpersons, Species Coordinators, and the Database Coordinator. The Administrative Advisors and the NAGRP Program Leader are ex-officio members.

Species Coordinators (Cattle, Sheep, Swine, Poultry, Horse and Aquaculture) work directly with their respective Species Sub-committees to facilitate gene identification/mapping activities for that species. The Database Coordinator maintains, updates and improves species databases, with input from Species Coordinators and Sub-committees. The Coordinators are selected by a competitive process, open to all Technical Committee members and administered by the NAGRP Program Leader and Lead Administrative Advisor. Applicants interested in the Coordinator positions will be required to submit a letter of intent outlining their qualifications and ideas for coordinating activities within their species (or across species for the Database Coordinator). Depending on the number of letters submitted, supplemental information will be requested for use in the review and selection process. A selection committee will be established by the NAGRP Program Leader and the Lead Administrative Advisor to review applications and select the coordinators.

The NAGRP Program Leader serves as the CSREES representative to NRSP-8. The Program Leader is responsible for overall leadership of the NAGRP and works closely with the NRSP-8 Technical Committee, Coordinators, and Administrative Advisors, who are representatives from the Regional Associations of Directors in the North Central, Northeastern, Southern, and Western Regions. Each Species Sub-committee selects one or more industry representatives, in consultation with appropriate national industry organizations. The Cattle Sub-committee will have representatives of both the beef and dairy industries. Industry representatives are invited to attend all Technical Committee meetings and serve as liaisons between animal industries and the NRSP-8 Committee.

Budget:
We request support of $400,000 per year. These funds will be distributed to the six Species Coordinators ($40,000-$55,000 per year) and the Database Coordinator ($130,000 per year for FY04 and FY07, and $100,000 per year for FY05, FY06 and FY08) (see Budget Table in Attachment 4). The requested funding will be used by the Coordinators to provide for communication and sharing of resources to enhance progress of the overall Technical Committee and will not be used to directly fund research programs. The Database Coordinator will be provided increased funding in FY04 and FY07 to purchase and upgrade hardware and software necessary for species databases.

Literature Cited:
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Band, M.R., Olmstead, C., Everts, R.E., Liu, Z.L. and Lewin, H.A. (2002) A 3800 gene microarray for cattle functional genomics: comparison of gene expression in spleen, placenta, and brain. Animal Biotechnology 13, 163-172.

Burt, D.W., Bruley, C., Dunn, I.C., Jones, C.T., Ramage, A., Law, A.S., Morrice, D.R., Paton, I.R., Smith, J., Windsor, D., Sazanov, A., Fries, R. and Waddington, D. (1999) The dynamics of chromosome evolution in birds and mammals. Nature 402, 411-413.

Coussens, P.M., Colvin, C.J., Wiersma, K., Abouzied, A. and Sipkovsky, S. (2002) Gene expression profiling of peripheral blood mononuclear cells from cattle infected with Mycobacterium paratuberculosis. Infection & Immunity 70, 5494-5502.

Crooijmans R.P.M.A., Vrebalov J., Dijkhof R.J.M., van der Poel J.J. and Groenen M.A.M. (2000) Two-dimensional screening of the Wageningen chicken BAC library. Mammalian Genome 11, 360-363.

Delgado, C., Rosegrant, M., Steinfeld, H., Ehui, S. and Courbois, C. (1999) Livestock to 2020; The Next Food Revolution. International Food Policy Research Institute, Food and Agriculture Organization of the United Nations, and International Livestock Research Institute, 83 pp., http://www.animalbiotechnology.org/livestock%20revolution.pdf

Eggen A., Gautier M., Billaut A., Petit E., Hayes H., Laurent P., Urban C., Pfister-Genskow M., Eilertsen K. and Bishop M. D. (2001) Construction and characterization of a bovine BAC library with four genome-equivalent coverage. Genetics, Selection, Evolution 33, 543-548.

Fahrenkrug S.C., Rohrer G.A., Freking B.A., Smith T.P.L., Osoegawa K., Shu C.L., Catanese J.J. and de Jong P. J. (2001) A porcine BAC library with tenfold genome coverage; a resource for physical and genetic map integration. Mammalian Genome 12, 472-474.

Groenen, M.A.M., Cheng, H.H., Bumstead, N., Benkel, B., Briles, E., Burt, D.W., Burke, T., Dodgson, J., Hillel, J., Lamont, S., Ponce de Leon, F.A., Smith, G., Soller, M., Takahashi, H., and Vignal, A. (2000). A consensus linkage map of the chicken genome. Genome Research 10, 137-147.

Hu, J., Mungall, C., Law, A., Papworth, R., Nelson, J.P., Brown, A., Simpson, I., Leckie, S., Burt, D.W., Hillyard, A.L. and Archibald, A.L. The ARKdb: genome databases for farmed and other animals. Nucleic Acids Research 29, 106-110.

International Human Genome Mapping Consortium (2001) A physical map of the human genome. Nature 409, 934-941.

Liu, H.C., Cheng, H.H., Tirunagaru, V., Sofer, L. and Burnside, J. (2001) A strategy to identify positional candidate genes conferring Marek's disease resistance by integrating DNA microarrays and genetic mapping. Animal Genetics 32, 351-359.

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McCoard, S.A., Fahrenkrug, S.C., Alexander, L.J., Freking, B.A., Rohrer, G.A., Wise, T.H. and Ford, J.J. (2002) An integrated comparative map of the porcine X chromosome. Animal Genetics 33, 178-185.

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Rosegrant, M.W., Paisner, M.S., Meijer, S. and Witcover, J. (2001) 2020 Global Food Outlook: Trends, Alternatives, and Choices. International Food Policy Research Institute, Washington, DC, 18 pp.

Sigurdson, C., Hogberg, M., Lamont, S., Hansen, L. and Keeton, J. (1999) FAIR 2002: Animal Products for the Next Millenium - An Agenda for Research and Education. Animal Agriculture Coalition and Federation of Animal Science Societies, 9 pp., http://www.fass.org/fair2002.pdf

Suchyta, S.P., Cheng, H.H., Burnside, J. and Dodgson, J.B. (2001) Comparative mapping of chicken anchor loci orthologous to genes on human chromosomes 1, 4 and 9. Animal Genetics 32, 12-18.

Vaiman D., Billault A., Tabet-Aoul K., Schibler L., Vilette D., Oustry-Vaiman A., Soravito C. and Cribiu E.P. (1999) Construction and characterization of a sheep BAC library of three genome equivalents. Mammalian Genome 10, 585-587.

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Attachments: [NRSP8_Att1_Objectives.doc] [NRSP8_Att2_Past_Accompl.doc] [NRSP8_Att3_Linkages.doc] [NRSP8_Att4_Budget.doc] [NRSP_Combined_Reports_for_NIMSS.doc]

Internal Linkages: AL, AR, CA-D, DE, HI, IA, IN, KY, LA, MI, MN, NE, NJ, NM, NYC, OK, RI, SC, TX, UT, WA, WI

External Linkages: Animal Health Trust, Newmarket, UK, City of Hope National Medical Center, Equine Research Institute, INRA, Louisiana State University School of Veterinary Medicine, Medical University of South Carolina, Michigan -Central Michigan University, National Marine FIsheries Service/Northwest Fisheries Science Center, Shelterwood Laboratories, Stormont Laboratories, Inc., Tufts University School of Veterinary Medicine, North Grafton, MA, USDA ARS NAA, USDA, ARS, USDA, ARS, BARC, ANRI, USDA-ARS, USDA-ARS-Avian Disease & Oncology Laboratory, University of British Columbia, University of California-Davis / School of Veterinary Medicine, University of Cincinnati Medical Center, University of South Carolina