List of Contents:

Justification Related current and previous work Objectives Procedures Expected outcomes Organization Funding requested

JUSTIFICATION:

The age of modern molecular genetics has arrived. Yesterday's theories relating genes to performance are now amenable to experimental proof and application. The rapid expansion of information and new technologies indicates that the molecular genetic revolution will continue for decades to come. In particular, the ability to examine the genome of an organism as a whole, rather than examining one or a few genes at a time has led to a new subdiscipline of genetics, termed "genomics".

New genomics technology initially was applied to model species (e.g., mouse, Drosophila) and to humans where strong financial support is available, especially for the Human Genome Program (HGP). As a direct consequence, our understanding of the genomes of these species is considerably advanced over that of agriculturally relevant organisms. Much of the credit for this advanced state of knowledge has been due to coordinated research efforts involving the sharing of technology, materials and data. Genomics research, being inherently holistic, is more efficient when conducted in this manner. For example, genetic and physical map development works best in a cooperative effort where each laboratory places markers on the same reference family map.

Animal breeders and geneticists recognized the potential applications of genomics to their own research many years ago but have been limited by the high upfront cost of developing a high throughput genomics lab 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 which authorized a USDA National Genetics Resources Program. Support for plant genomics (and plant genome coordination) developed more quickly than on the animal side. Subsequently, a task force was appointed by the SAES, CSRS and ARS to determine how the Animal Genetic Resources Program should be structured. This group, chaired by Neal Jorgensen, recommended the establishment of two coordinated programs: a National Animal Genome Research Program (NAGRP) to be led by CSRS (now CSREES) and a National Animal Germplasm Program, to be led by ARS.

In order to stimulate cost-effective animal genomics research and to provide opportunities for wide participation, NRSP-8 was initiated in 1993. This provided a mechanism to help coordinate US genome mapping efforts in cattle, sheep, swine, and poultry; a horse project was added in 1997. 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 genomic maps (both physical and genetic), establish databases for sharing and communicating information, and provide leadership in establishing research priorities at a national level. Coordinators were selected by an open, competitive process. (Due to many common interests, cattle and sheep together have a single Species Genome Committee but have separate Species Coordinators.)

Coordinated research efforts to map within and sometimes across species have been substantially enhanced by NRSP-8. Through the distribution of reference family panel DNAs, PCR marker primers, DNA probes and information, individual genetic maps for cattle, sheep, swine, and chicken now include over 1200, 600, 1100, and 700 markers, respectively. It should be emphasized that cooperation extends beyond the NRSP-8 Technical Committee to include a large number of laboratories, world-wide, that have played active roles in advancing animal genomics. Often more than one map or mapping population exists for a species, but these have been and are being consolidated into consensus maps due to the exchange of markers and data. Databases containing genetic and physical maps, references, related information, and links to other sites are now publicly accessible via the Internet. Newsletters and participation in meetings have helped the coordinators relay research information and opportunities.

To identify, map, and characterize genes involved in quantitative traits of economic importance for livestock species, continued advancement in agricultural genomics must be maintained. Current high priorities include increased marker saturation, the development of clone-based integrated genetic/physical maps, high resolution comparative maps, and better integrated databases. These demands increase the need for coordination, especially if we are to maintain our links with ongoing international projects, and fully realize the value of information generated by the HGP. Within the next 5-10 years, it is expected that both the human and mouse genomes will be fully sequenced (about 3 billion base pair each), and judicious use of these enormous databases will be critical to the future of all of biology, in particular the future of animal agriculture.

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 Phase I of their recent research prioritization process (August, 1996). 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." In addition, interagency discussions are on-going about the development of a National Food Genome Program as a National Initiative (Neal Jorgensen and Colin Scanes, personal communication). Furthermore, the NAGRP was selected to receive a 1997 Secretary of Agriculture Honor Award for its contributions to agriculture and science. These are three clear indications that NRSP-8 related research is viewed as a top priority by leaders of the U.S. agricultural community.

RELATED CURRENT AND PREVIOUS WORK:

The Regional Research (RR) projects cited below and this proposed renewal of NRSP-8 are designed to be highly complementary. To a large extent, the research being conducted in these RR projects is dependent on the reference genome maps to be further developed as part of NRSP-8. Animal genomics requires parallel advances in two complementary approaches: 1. Understanding the basic principles of genome organization and function as illustrated by comparative framework genome maps, and 2. The ability to detect, isolate, and analyze specific beneficial alleles (quantitative trait loci, QTL, a subset of which are ETL, economic trait loci) in useful populations. The basic principles of genomics apply throughout biology and are most effectively and efficiently analyzed through close cooperation across all relevant species. Therefore, NRSP-8 highlights framework genome maps and comparative gene mapping. QTL alleles are usually species-specific and often confined to a given population of interest, so this research is highlighted in RR projects, most of which focus within a single species or related species group.

NC-168: Advanced Technologies for the Genetic Improvement of Poultry is a revised project approved until 9/30/02. Its objectives are to: (1) Utilize modern molecular and breeding technologies to identify, locate, isolate and characterize poultry genes of economic importance, (2) Develop methods for locating new genetic variation in poultry by gene transfer and chromosome alteration, and (3) Develop, compare and integrate emerging technologies with classical quantitative genetics for improvement of economic traits in poultry. The focus of NC-168 is on QTL analysis, transgenic technology, and quantitative genetic theory related to poultry.

NC-209: Genetic Improvement of Dairy and Beef Cattle Using Molecular Markers is a revised project approved until 9/30/02. Its objectives include: (1) Identify and characterize structural variation in genes and gene products that influence traits of economic importance, and (2) Develop methods to use molecular technologies in applied breeding programs. NC-209 focuses on QTL analysis and marker-assisted selection in cattle.

NC-210: Positional and Functional Identification of Economically Important Genes in the Pig is a revised project approved until 9/30/02. It has two objectives: (1) To positionally clone economic trait loci in the pig, and (2) To identify and analyze the function and expression of genes that regulate traits of economic importance in the pig. The focus is on isolation and expression analysis of relevant swine genes.

NC-220: Integration of Quantitative and Molecular Technologies for Genetic Improvement of the Pig is approved until 9/30/01. One of its objectives is to identify genes that contribute to economically important traits and evaluate the potential for genetic improvement. NC-220 focuses on QTL mapping and marker-assisted selection in swine.

NCR-21: Quantitative Genetics is approved until 9/30/01. Its objectives are: (1) To develop and test quantitative genetic theory and methodology relevant to animal and plant improvement and to an understanding of the genetics of natural populations, (2) To evaluate application of biotechnology for improvement of quantitative traits in plants and animals and for its impact on natural populations, and (3) To provide leadership for the interface between biotechnology and quantitative genetics and their joint applications. NCR-21 focuses on mathematical analysis and use of model organisms to support quantitative genetics theory. (It also helps organize the Gordon Conference series, "Quantitative Genetics and Biotechnology".) NCR-21 provides theoretical research that is complementary to NRSP-8.

NE-60: Genetic Basis for Resistance and Immunity to Avian Diseases is approved until 9/30/98. One of its objectives is to identify and characterize genes and their relationship to disease resistance in poultry. NE-60 focuses on the function of genes involved in the immune response.

WRCC-1: Beef Cattle Breeding in the Western Region is approved until 9/30/00. This project focuses on the use of quantitative genetics and applied breeding to improve beef cattle. Among its activities is the development of a DNA repository of selected research stock, and several members are applying molecular genetic technologies in their research.

There is some overlap between the Technical Committee membership in NRSP-8 and various RR projects which is beneficial for data exchange and coordination. Naturally, NRSP-8 scientists are not only interested in the generation of fundamental genome information, but also in the application of these results to commercially relevant questions such as QTL identification and marker-assisted selection. Although this overlap may occasionally result in some duplication of reporting (biology doesn't respect administrative divisions), it does not result in wasteful redundancy, because, as described above, the respective research foci are complementary and must be pursued in parallel.

Care has been taken in eliminating functional overlap between NRSP-8 and RR projects in both this renewal application process and in recent renewals of some of the projects through joint discussions between the respective Technical Committees. It was agreed that NRSP-8 should be renewed as a multispecies project to continue development of the framework genome map for each species, to focus on comparative genome mapping across species, and to maintain the animal genome databases. NCR-21 takes a similar cross-species approach, but in quantitative and theoretical analysis, rather than in genome mapping. The other RR projects are focused on single species and on unique sets of genes and/or ETL alleles rather than on the whole genome. As described, the two approaches are complementary, as reflected by the fact that both NRSP-8 and several of the RR projects have often met in conjunction (one following the other) to facilitate cross-talk and as a convenience for those members in both NRSP-8 and a RR project. As of 1997, these meetings also were in conjunction with the Plant and Animal Genome Meetings, an even greater reflection of the biological unity of genomics and the sharing of techniques and ideas throughout the agricultural genetics community. These joint meetings also save time and travel costs, as members are able to accomplish many objectives with a single trip.

OBJECTIVES OF NRSP-8: We propose to:

1. Develop high resolution comparative genome maps aligned across species that link agricultural animal maps to those of the human and mouse genomes.

2. Increase the marker density of existing linkage maps used in QTL mapping and integrate them with physical maps of animal chromosomes.

3. Expand and enhance internationally shared species genome databases and provide other common resources that facilitate genome mapping.

PROCEDURES:

Objective 1. Develop high resolution comparative genome maps aligned across species that link agricultural animal maps to those of the human and mouse genomes.

The ultimate goal of the animal genome research is to facilitate the identification, cloning, and characterization of genes responsible for economically important traits. Linkage maps of polymorphic markers are being developed in agriculturally important species and are already being utilized to map ETL. The next step, identifying and cloning genes responsible for these traits, armed only with knowledge of their chromosomal localization, is a formidable one. Even in humans and mice, for which financial resources are comparatively abundant, map-based cloning is an arduous task. Positional cloning in humans, however, is rapidly being replaced by "positional candidate cloning," a strategy in which candidate genes are generated from high-density transcription maps across the large intervals (potentially containing hundreds of genes) to which traits can be genetically mapped. This approach and the detailed maps of functional human genes that support it, also offer special opportunities for the animal genome research community. The identification of regions of chromosomal homology between humans (or mice) and agriculturally important animals will also provide candidate genes on the human map for many animal ETL of agricultural interest. It then becomes much easier to locate the homologous animal candidate gene(s) to be tested. Thus, the development of high resolution comparative maps will permit animal geneticists to extrapolate candidate genes directly from human and mouse gene maps to animal ETL maps.

Although the human genome is destined to be the prototypic genome for comparative mapping purposes, the mouse genome map cannot be ignored. The designated mammalian "model organism" of the human genome initiative is also a valuable laboratory model for identifying both QTL and single genes related to growth, reproduction and disease. Many of these genes are likely to be homologous to ETL in livestock genomes. Furthermore, the HGP has already led to the development of a high quality mouse-human comparative map that serves as a model for what we hope to achieve with agricultural animal species.

Comparative maps of economically important animals relative to humans and mice will be essential for agriculture to directly benefit from the human genome initiative. However, comparative maps between agricultural animal species are also needed to derive maximum benefit from the animal genome effort. Homologous genes related to muscle composition, reproductive performance or disease resistance, for example, will be important to more than one animal industry. Especially valuable will be comparative maps between genomes that are most closely related evolutionarily, for example, sheep and cattle or chicken and turkey. Cattle markers are already routinely tested and used in the sheep genome mapping effort.

The specific aims to be addressed in objective 1 are as follows.

1. Common marker panels. Facilitate the mapping of a common set of homologous genes in all relevant species. This will involve prioritization of a common set of genes to facilitate the most efficient use of resources and the development of techniques that improve the speed and cost-efficiency of comparative mapping.

2. Comparative map resources. Facilitate the development and distribution of resources for high-resolution comparative mapping, for example, ZOO-FISH painting reagents, radiation-hybrids, reference mapping family DNA panels, and primer sets with the potential to amplify homologous genes in more than one species.

3. Comparative map data sharing. Facilitate the development of comparative genome databases that include agriculturally important animals. This will include continued development of species databases in formats compatible with merger and cross-reference with each other and with human and mouse genome databases.

Since relatively few animal geneticists regularly work in more than one or two species, comparative mapping inherently requires sharing results and DNA probes between investigators and across species. No RR project is set up to do this. The mechanisms by which NRSP-8 will facilitate comparative mapping are common to all three objectives and will be discussed below (Mechanisms section). As will be described later, aims 2. and 3. naturally interface with some of the aims of objective 3.

Objective 2. Increase the marker density of existing linkage maps used in QTL mapping and integrate them with physical maps of animal chromosomes.

Mapping QTL is inherently imprecise, making it difficult, if not impossible, to localize them more accurately than to within 5-10 cM intervals. This implies that maps with high resolution and excellent alignment with those of humans or mice will be required to understand and fully take advantage of QTL. An integrated genome map consists of a genetic linkage map with a high density (ca. 1-2 cM) of widely polymorphic markers that is aligned with a complete physical map consisting of ordered, overlapping clones from large insert libraries. Integrated maps of the type and quality described are presently available in two vertebrate species, human and mouse. Two basic components were required to assemble those maps: large arrays of markers, a subset of which can be ordered by genetic linkage mapping, and complete genomic libraries in large insert vectors, i.e., yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs). Radiation hybrid mapping panels can also be of great value in the development of integrated physical/genetic maps. Significant progress has been made in the generation of both large insert libraries and useful markers for cattle, sheep, swine and chicken. However, the existing marker collections are insufficient, either for whole genome, high resolution QTL mapping or for the generation of complete integrated maps. A less serious problem is that existing large insert libraries are relatively few and of limited availability in some species.

The genetic linkage maps for agricultural animal species presently available demonstrate a fairly high level of coverage (ca. 95% of markers in linkage groups) and many of the markers have widespread utility for animal breeders. However, the average marker spacing is approximately 3-10 cM, depending on the species in question, which corresponds to a distance of roughly 2-10 million base pairs (Mb) of DNA, and there are many gaps much larger than this. Since even the best large insert libraries have average inserts of 1 Mb or less, present marker resolution is insufficient for map integration. Furthermore, many of the available markers are not sequence-tagged site (STS) loci suitable for physical map assembly and/or are not highly polymorphic for wide utility in ETL mapping crosses (resource populations). This is especially true for commercial line crosses that are likely to be more uniform genetically than the divergent experimental crosses that have been heavily used to date. Thus, it is clear that better marker densities are required for both genetic and physical mapping. To put this in context, the human genetic map is about the same size (in cM) as those of the major agricultural animal species. Even for the first generation integrated human genome map, over 15,000 STS markers were used.

In the most general sense, all genome mapping involves binning (or pooling) a collection of linked markers into ever-smaller subsets such that a local order is generated. Thus, the goals of genome coordination are to assist with the use of common marker sets and common binning pools, such that data can be collected and assembled into shared framework maps with high resolution, accuracy, and utility. Markers can be binned by meiotic breakpoints, as in linkage mapping, by radiation-induced breakpoints, as in radiation hybrid mapping, or by DNA breaks induced in recombinant DNA library construction, the basis of high resolution physical maps.

The specific aims to be addressed in objective 2 are listed below. The means by which they will be achieved are described later in the Mechanisms section.

1. More mapped markers. Framework genetic linkage maps should approach a theoretical resolution of about 1-2 cM. This will require that 3,000 (or more) markers be placed on the framework map for each species.

2. Maps/markers of higher utility. As much as possible, framework markers should be STS loci, preferably genetically variable STS markers such as microsatellites. Such markers are most useful for correlating physical maps with ETL map data. In addition, STS markers that are within expressed genes (expressed sequence tags or ESTs) are optimal for comparative mapping as described in objective 1.

3. Binning pools for mapping. Improved framework map resolution also requires that markers be distributed in smaller bins. This involves common use of reference panels with more meiotic breakpoints, combining reference panel data into consensus maps, development and use of radiation hybrid mapping panels, and/or physical mapping of STS markers using high quality, large insert DNA libraries.

Objective 3: Expand and enhance internationally shared species genome databases and provide other common resources that facilitate genome mapping.

Coordination and sharing of mapping resources are vital to streamlining research and to avoiding duplication. In particular, shared resources allow wider participation of scientists who have limited local access to equipment and supplies. Researchers and breeders also need unimpeded access to databases, together with the necessary tools for queries and analysis in order that increased understanding can be developed from a synthesis of many individual experiments. Inherent in the top-down approach of genomics, along with the impressive data generation power of modern technology, is the need to deal with large, complex data sets in a meaningful way. A new discipline has emerged focused on this challenge: Bioinformatics.

Genome databases that underpin the needs of the livestock genome mapping programs have been developed through productive international collaborations. The initial model adopted for pigs, chickens and sheep was based on the mouse genome database - GBASE. More recently, the bioinformatics group at the Roslin Institute has developed a revised model for livestock genome databases - Arkdb. Editorial and curatorial functions are shared by scientists in the United States and elsewhere. One of the major accomplishments of the NRSP-8 has been to support the development of databases for each species. This support assisted in the creation of these databases and their continuing evolution, such that they now include linkage mapping, physical mapping and information on individual genes, markers and mapping materials. These databases also include information on mapping resources and published references. The continued development and maintenance of these shared databases (and their expansion to the horse genome project) is central to the shared activities of NRSP-8.

The specific aims to be addressed in objective 3 include:

1. Improved databases and communication. Existing genome databases will be improved based on rapid developments in bioinformatics technology. New data will be added, databases will become more fully networked, and new search engines will be employed. Other communication mechanisms such as newsletters, email servers, Internet homepages, and the annual NAGRP meeting will be enhanced.

2. Shared mapping resources. Shared resources will be maintained and expanded to enhance the cost-effectiveness of genome mapping and its applications. These include mapping panel DNAs, large insert libraries, comparative mapping resources, and a variety of primers for PCR-based marker mapping.

Mechanisms: The ways in which NRSP-8 will support the three objectives and their individual aims can be grouped in three categories: Communication, Sharing Materials and Sharing Data. These will be outlined below, along with examples of their applications to the individual objectives.

Communication. First, by sharing plans for future research and results of past research, efficient, coordinated mechanisms can be developed for improving existing framework (consensus) maps. One example of this are the chromosome workshops that have been and are being arranged for many specific swine and bovine chromosomes. In addition to the single species chromosome workshops held to date, interspecies comparative chromosome workshops will occur to ascertain regions of shared gene order. Furthermore, the NRSP-8 Technical Committee can prioritize common genes to place on maps that will most effectively answer the critical questions of genome evolution and comparative map utilization. Technical Committee meetings will facilitate interaction between groups working in different species, so that they can develop the cross-species collaborations that are essential for comparative map generation. NRSP-8 has taken the lead in coordinating its annual meetings jointly with related RR committees and, more recently, arranged to conduct these meetings as part of an expanded Plant and Animal Genome (PAG) meeting. This provides greatly enhanced opportunities for information and technology transfer between international scientists in all aspects of agricultural genetics in both the public and private sectors (attendance was about 600 at the first joint PAG meeting in January, 1997, and is expected to be 800-1000 in 1998).

Other communication mechanisms: The publication of newsletters and other printed material, along with the development of World-Wide Web (WWW) species homepages and an on-line-computer discussion group for gene mappers (ANGENMAP) have proven very valuable and popular as ways to share information. These provide user-friendly ways for the participating scientists to keep abreast of each others' activities, available resources, upcoming meetings, and general advances in technology and research. They encourage better communication and cooperation among the participating scientists, worldwide. Perhaps even more important, newsletters and WWW homepages provide very effective outreach functions in keeping potential beneficiaries in wider agricultural and consumer group circles aware of and involved in the advancements in agricultural genetics. Our newsletters and homepages are seen by thousands of people, many of whom are not gene mappers but simply interested agricultural scientists, consumers, students and hobbyists. These activities will continue and expand. As another example, animal geneticists have recently joined their plant colleagues in generating the Probe newsletter for agricultural genomics.

Sharing materials. As described in the Critical Review, the sharing and distribution of a variety of panels, primers and libraries is already well underway and has proven very successful. The goal will be to increase the utility of these resources, especially as scientific advances make new types of markers and materials applicable. This will speed applications of the maps to specific agricultural problems. Shared markers will be vital as enhanced maps provide more and more opportunities for fine mapping of ETL and tests of marker-assisted selection strategies.

DNA panels and libraries: Family materials for gene mapping and ETL research are difficult and expensive to develop. Shared use of a DNA panel adds value (map information) to that panel for everyone involved. The coordination effort will be directed to collecting DNA from international and national mapping and ETL families and sharing that with members of species committees. This allows for joint genetic framework maps and for joint ETL analyses. Similarly, somatic cell hybrid panels (including radiation hybrids) and large insert libraries function analogously to family panels as binning resources for physical maps rather than linkage maps. Several BAC libraries for various species have been made at Texas A&M and elsewhere (see Critical Review). The maintenance and distribution of mapping resources like BAC or YAC libraries and somatic cell hybrid panels requires significant effort and expense, and this process will be facilitated and supported by species coordinators. This avoids duplication and increases the power of the research at a fraction of the cost. In addition, large insert DNA clones from contiguous regions (contigs) will be shared for fine structure comparative mapping to answer more detailed questions about genome evolution mechanisms.

Primers and other marker materials: Panels of microsatellite (and other STS) markers will continue to be developed and enhanced, and the requisite PCR primers will be provided to interested investigators to increase the resolution, accuracy, and utility of framework marker sets and maps. Sharing of primers for ETL analyses and mapping research have proven very valuable. A total of approximately 1000 primer pairs have been shared with participating members (typically 30 or more participants/species) at a fraction of their cost if each station made them individually. In the future, a variety of comparative mapping probes will also be developed and/or distributed using coordination funds. These include comparative anchor tagged sequence (CATS) primer pairs for PCR-based comparative mapping, Type I gene clone DNAs and/or primers and ZOO-FISH comparative cytogenetic probes, used in karyotype-based comparative mapping.

Sharing data. For comparative mapping to be most effective, the individual species databases must be able to directly exchange information. To some extent this process has begun, with links of existing databases to human (or mouse) maps and databases. The development of the next generation of database, named TCAGdb for The Comparative Animal Genome database, is already well underway (see Swine section of Critical Review). This will pull together data from the single species databases for cross-species comparisons, as will be required for true comparative mapping. TCAGdb is based on the Arkdb model, a generic model applicable for all relevant species. (Arkdb versions of some of the species databases have recently been installed, see Critical Review). This advanced database has all the previous capabilities of providing information on linkage and physical mapping data. In addition, information on primers and mapping tools will be greatly expanded. Data entry tools will be improved such that entry is faster and more complete. Over the next 5 years, we can expect rapid advances in the bioinformatics field, as it struggles to keep up with the massive amounts of human, mouse, and model organism genome data being generated. NRSP-8 support will allow for the judicious application of the most effective of these advances to the agricultural animal genome databases. In the Internet environment, the actual location(s) of the database is not critical. In fact, at least two nodes for each existing database are desirable, to provide a back-up for one another and to insure rapid user access. It is envisioned that the Coordinators for each species will be co-editors (with appropriate international collaborators) for each of the respective databases. Editors, with the assistance of curators at the node sites, will receive and evaluate data from participating scientists, ask for revisions if necessary (e.g., for database consistency), and approve data for inclusion. Coordinators (and journal editors)will be responsible for requiring that map data that support publications are submitted by the authors. Curators will also be active in technical improvement of the databases. For maximal cost effectiveness, it is anticipated that two or more Coordinators will share one primary US node for their databases, supported by a single curator (see budget).

EXPECTED OUTCOMES:

1. Framework genome maps for agricultural species will be improved to a resolution (average marker spacing) of 1-2 cM from the existing 5-10 cM.

2. Physical maps based on cloned DNA fragments will be developed that cover large contiguous chromosomal domains or, in some cases, whole chromosomes.

3. Comparative maps will be available which link the genomes of agricultural animals to those of human and mouse.

4. Together, the first three outcomes will facilitate the isolation and characterization of ETL-encoding genes from several species' genomes, most often via the positional candidate approach to gene cloning (see objective 1). ETL will be identified that relate to meat, milk, egg, and wool productivity, disease resistance, and reproductive efficiency. Based on this information, breeding schemes will be designed to take maximal advantage of the existing genetic diversity of agricultural animals.

5. New genetic tests will be developed for productivity and disease resistance traits. These tests will be applied by the commercial sector to make food (and other animal products) safer and more economical and to generally improve animal health and welfare.

6. Internationally-shared species genome databases will be enhanced such that genomics information will be readily available and widely used.

7. Marker primer pairs, DNA mapping panels, large insert libraries and other relevant mapping resources will be obtained by participating laboratories at little or no cost.

All the above outcomes will stimulate interest and enhance expertise in animal genomics to speed its application to problems of economic interest.

ORGANIZATION:

NRSP-8 supports the National Animal Genome Research Program (NAGRP), which is organized to link and facilitate animal genome research efforts with universities, SAES, CSREES, ARS, and the animal breeding industry.

National Animal Genome Technical Committee. The Technical Committee is composed of participating scientists appointed by their SAES Directors or other administrators of each cooperating organization. The Technical Committee meets annually and provides guidance to the NAGRP. The members of the Technical Committee are subdivided into Species Committees to interact and work with the designated Species Coordinators. Each year the Technical Committee elects a chairperson and a secretary; the Species Committees also elect their own chairpersons and secretaries. The chairperson of the Technical Committee calls and conducts meetings of the Technical Committee, coordinates the activities of the Species Committees, keeps the NAGRP Program Leader informed, and prepares and submits an annual report of Technical Committee activities and accomplishments to the NAGRP Program Leader and Administrative Advisors. The secretary prepares and distributes minutes, maintains a record of participating scientists and organizations, and establishes a permanent list of publications from the project.

Executive Committee. The NRSP-8 Executive Committee is designated to deal with activities between scheduled meetings of the full Technical Committee. The Executive Committee is composed of the Technical Committee Chairperson and Secretary, Species Genome Committee Chairpersons, and Species Coordinators. The Administrative Advisors and the NAGRP Program Leader are ex-officio members.

Species Genome Committees. The Species Genome Committees are composed of members of the NRSP-8 Technical Committee with active genomic research programs within that species. The Species Committees identify and establish criteria for the acceptance, preservation and use of reference and resource families, suggest priority areas for mapping and ETL research in their species, identify needs for genetic markers and other shared materials, and aid in the growth and development of species databases. These activities are planned in concert with the Species Coordinators.

Species Genome Coordinators. Five Species Coordinators (Cattle, Sheep, Swine, Poultry, Horse) will be selected by a competitive process, open to all Technical Committee members and administered by the NAGRP Program Leader and Lead Administrative Advisor. They will seek input and advice in doing so from the Species Genome Committees. Current Species Coordinators (selected in a previous competition) will be allowed to reapply along with other interested scientists. The Species Coordinators are closely linked to the NAGRP Program Leader and the Species Genome Committees. They work directly with and for their respective Species Committees to coordinate gene mapping activities for that species. They participate in the establishment of a genome mapping database, facilitate the entry of genetic information into the databases, facilitate the summarization and interpretation of genomic data, periodically revise and distribute maps, serve as a repository for genetic materials, and distribute reference DNA panels, genetic probes and markers, and other materials as determined by the Species Committee.

Administrative Advisors. The Regional Associations of Directors in the North Central, Northeastern, Southern, and Western Regions will designate their Regional Representatives to NRSP-8. These Administrative Advisors will provide policy guidance to the Technical Committee and work closely with the CSREES Representative (NAGRP Program Leader) on administrative, programmatic, and budgetary matters. The current Administrative Advisors are:

	North Central		Colin G. Scanes (Lead Administrative Advisor, Swine)
	Northeastern		James A. Stewart (Poultry)
	Southern		James A. Boling (Cattle, Horse)
	Western		Gary P. Moberg (Sheep)

CSREES Representative. The NAGRP Program Leader, Richard R. Frahm, 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, Species Coordinators, and Administrative Advisors. Other responsibilities of the Program Leader include providing liaison with the NRI Competitive Grants Program, serving as USDA link to international genome activities, providing linkage to the National Animal Germplasm Program, and being an advocate for animal genome research activities within the USDA.

Industry Representatives. Each Species Genome Committee will select one or more industry representatives, in consultation with appropriate national industry organizations. (Cattle 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 Committee. (This does not preclude invitation of additional representatives or open invitations for industry-affiliated participants at the discretion of the Species Genome Committee in question.)

Reporting. The Technical Committee will prepare an annual progress report that reviews project accomplishments and outlines future plans. Publication of genomic information and results will be in scientific journals and other media (including the Internet) to provide public access to the benefits of the genomic research fostered by this project.

FUNDING REQUESTED:

We request continued support for NRSP-8 at the existing level of $380,000 total per year. No increase is requested despite the addition of the Horse Genome Committee and the considerable increase in activity and data generation during the previous support period. This is feasible primarily due to two factors: First, the initial development of databases and related information resources for cattle, sheep, swine and poultry has been completed with the intent to use similar formats in the future wherever possible. This allows us to cost-effectively consolidate database activities as described below. Second, collaborations that have been developed with international colleagues will result in cost-effective sharing of efforts and data. Furthermore, shared costs from the Coordinators' institutions will continue (both direct and in-kind) at a level similar to or in excess of that requested.

The initial distribution of the requested annual funding will be as follows:

	$60,000		Cattle Coordinator
	$60,000		Swine Coordinator
	$50,000		Poultry Coordinator
	$45,000		Sheep Coordinator
	$45,000		Equine Coordinator
	$120,000		Maintenance and upgrade of two database nodes ($60,000 each), one to be the primary node for cattle/sheep/equine and the backup database node for poultry/swine; the second being primary for poultry/swine and backup for cattle/sheep/equine

Budget Justification. The requested RRF funding is to support the facilitation activities of the five Species Coordinators and will not be used to directly fund research programs. Coordinator funding is used for the support of all the outlined coordination activities, including editing databases, developing and providing shared primers, DNAs and other resources, and maintaining communication within species technical committees and with outside collaborators.

It is proposed to fund two database sites. Each site would have a database curator supervised by the Species Coordinator located at that site. One site would serve as the primary database node for cattle, sheep and equine and the backup node for swine and poultry, with the other being the primary site for swine and poultry and backup site for the other species' databases. Backup nodes provide security in case of a computer or network failure at the primary node or an alternative contact point in case of network traffic delays during peak use. Information at the primary nodes will be regularly (e.g., nightly) replicated at the backup nodes. Each Species Coordinator will continue to serve as the database editor for that species. Funding for the two database sites will be for the requisite computer hardware and software, computer maintenance, and salary for the computer specialist to update and improve databases, data entry and curator activities

Budget Authorization. Coordinators will submit budget requests and reports annually. Allocations will be reviewed annually and the distribution will be revised, if necessary, by the NAGRP Program Leader and the four Regional Administrative Advisors.

Types of Expenditures: Salaries are for professional and technical support staff for developing and distributing genetic materials and for data input and operation of the databases. Salaries of Species Coordinators and collaborators are contributed by the participating institutions. Supplies include genome mapping supplies and materials to be shared with Species Committee members, computer supplies and software for maintaining databases and computer information servers, shipping costs, publication costs, postage, and newsletters associated with the Technical Committee activities. Equipment is primarily computer equipment for the databases and storage/handling of genetic materials. Funds are requested to support travel of the Species Coordinators and/or their representatives, to important scientific meetings which provide opportunities to facilitate the coordination of genome mapping efforts in the U.S., along with those of other countries.

• Presentation: NRSP-8

• Species Coordinator Roles

• Pig Genome Coordination Structure