NRSP008: National Animal Genome Research Program
Statement of Issues and Justification
Prerequisite Criteria: Mission
INTRODUCTION
The National Research Support Project (NRSP)-8 supports the USDA-CSREES National Animal Genome Research Program (NAGRP) which has played a major role in facilitating genomic discoveries in farm animals and aquaculture species. The recent "Blueprint for USDA Efforts in Agricultural Animal Genomics 2008-2017" (herein Blueprint ) portrays a pyramid in which Science to Practice (application) is supported by Discovery Science (basic research) which in turn is supported by Infrastructure. It is the mission of NRSP-8, since inception, to provide and enhance Infrastructure. This mission is accomplished providing shared genomic resources (tools, reagents, DNA, data) to its members and by leveraging its own limited resources with those from federal (NIH, USDA-NRI), international, industry and state sources. NRSP-8 stimulates and coordinates new initiatives by providing national leadership recognized by our stakeholders. Communication is critical to the shared resource model and NRSP-8 fosters communication among members and stakeholders through newsletters, email discussion groups, our bioinformatics program and contributions to meetings such as the annual International Plant and Animal Genome (PAG) conference.
The NRSP's are specifically focused on "the development of enabling technologies, support activities . . . , or the sharing of facilities needed to accomplish high priority research". As demonstrated by past activities (Attach. 1, 2003-08 Accomplishments) NRSP-8 has enabled substantive progress in agricultural animal genomics research, on a multi-species basis in a variety of ways, thereby meeting the ideals and vision of the unique NRSP model to create a mechanism which provides magnified benefits, promoting collaborative partnerships and novel opportunities for high priority research. There are three key and interrelated reasons for why animal genomics is a great fit for the NRSP mechanism:
a. Cost. Genomics technology is high-priced. Not only is the equipment costly, but its fundamental nature is high throughput translating to higher total cost (although a lower cost per data point). These high costs frequently exceed funds available to any single investigator, especially within the agricultural research community. Even when the initial development of a resource (e.g., bacterial artificial chromosome [BAC] libraries, single nucleotide polymorphism [SNP] and gene expression "chips") is funded by the USDA-NRI Tools and Reagents program or by the NIH, the distribution fees are often prohibitive to members of our research community or, at the very least, serve as an initial disincentive to exploring new technologies.
b. Efficiency of Sharing. Genomics resources (often products of robotics) are premier examples of the "volume discount". By bringing together many researchers, none of whose usage alone would justify obtaining these tools at a reasonable price, NRSP-8 coordination has been able to deliver a variety of tools to reach many, if not all, of our members. Equally important, NRSP-8 coordinators have leveraged their support base many times over by developing cost-sharing arrangements with NIH-, USDA-, and industry-funded projects and with international initiatives.
c. Cooperation. Genomics research is inherently a cooperative venture. Consider for example, mapping: if everyone individually maps a few genes using their own private animal cross, the result would be many small genetic maps of little use to anyone else. Whereas, if everyone works together with a common population, a critical mass of linkage relationships develop allowing a framework map across an entire genome (the whole being greater than the sum of its parts). Prior NRSP-8 support stimulated and organized a cooperative and collaborative research approach to the benefit of numerous stakeholders.
NRSP-8 renewal objectives are described in the Implementation section and in Attach. 2 (Objectives-Outcomes), however, it is relevant to briefly outline how these fit the unique mission expected of a National Research Support Project.
Our first objective is to provide genomic tools and sequence information to our members and stakeholders. As noted, such items are frequently unavailable or unaffordable to individual researchers. Beyond this, some members initially may be unfamiliar with available or novel genomic approaches or be reluctant to commit the time and resources to adopt them. As a community, NRSP-8 efforts stimulate new research avenues and reduce the barriers presented by cost and lack of expertise.
Our second objective is to enhance development and availability of experimental families, lines and populations possessing unique, interesting and economically important phenotypes. Previously, our focus was on shared populations for the development of framework linkage maps (international reference map populations). Now, our focus shifts to centralized animal genetic resource populations that are intensively-phenotyped and widely available. Intensively-phenotyped means that groups with the expertise and desire to collect different types of trait data would share a common population. Historically, Experiment Stations maintained their own unique research populations for many, if not all, agriculturally-relevant species. This is not the current model, as many institutions have eliminated resource families and genetic stocks and thus farm animal research populations are essentially endangered species. Application of animal genomics focuses on elucidating the connection between the properties of the genome and the phenotype (the phenome), i.e., traits: economic, quantitative or otherwise. Without the specialized families, lines and populations, there are no phenotypes and the usefulness (application) of genomics is limited. These vanishing resource populations are as fundamental a part of the infrastructure required for successful animal genomics research as are BAC libraries and microarrays, and therefore we place an especially high priority on this objective for the renewal period. It is important to emphasize that the populations themselves as well as their phenotypes and genotypes are of critical need to make the most of the available genomic information. Thus, both DNA samples and phenotypic data must be freely shared.
The shared resources model that has served NRSP-8 so well is reliant on extensive real-time communication. Thus, our third objective is to maintain as well as enhance communication and further improve the bioinformatics base so fundamental to genome analysis and interpretation. Our mission is to provide the infrastructure for our members to conduct modern animal genomics research. This includes access to data, enhanced electronic communication mechanisms and the development of new ways to examine the data (e.g., standardized ontologies, metagenomics). The enormous datasets generated by genomic technologies can be likened to the digital stream of bits that drive computers. Without the bioinformatics equivalent of the graphic interface that convert digital bits to what is visualized on a monitor, the genomics data outputs alone are frequently unintelligible. Bioinformatics (Obj. 3) is the translational language of systems biology and is as essential to the infrastructure as are the genomic tools (Obj. 1) and the requisite genetic populations and phenotypes (Obj. 2).
In summary, NRSP-8 provides enabling technologies and support activities that would otherwise be unavailable to most, if not all, agricultural animal geneticists/genomicists. This includes not only our own members but also commercial and international stakeholders. Finally, it should be noted that our ultimate stakeholder is the public who expect new and enhanced technologies for improved efficiency and welfare of animals and who often turn to NRSP-8-sponsored web sites, newsletters, and membership to help understand and appreciate advances in domestic animal genomics.
Prerequisite Criteria: How does this NRSP pertain as a national issue?
a. National Scope. It is obvious by the National Animal Genome Research Program name and the diversity of our membership that NRSP-8 addresses a national, and indeed an international, issue. The 2001 document "A Science Roadmap for Agriculture" (herein 2001 Roadmap ) in its "SPECIFIC OBJECTIVES OF A NATIONAL RESEARCH PROGRAM" for Challenge 2 ("We can develop new products and new uses for animals"), lists as its first objective: "Close current science "gaps" in animal agriculture through expanded programs in functional genomics, proteomics and bioinformatics." Clearly, this is exactly the research for which NRSP-8 seeks to build the infrastructure.
A major strength of NRSP-8 is its multi-species, comparative biology basis, and this is a factor regarding our national scope. Virtually any Experiment Station involved with animal agriculture includes some elements that are relevant to the NRSP-8 mission. This derives from the similar technologies employed regardless of species and the evolutionary relatedness of their genomes. It is also of note that several NRSP-8 species generate multiple products (cattle: meat and milk; chicken: meat and eggs; sheep: meat and wool). Even though the populations employed may be specialized for one or the other commodity, their genomes are still extremely similar. Thus, a Station might have limited broiler chicken research but still benefits from chicken genomic research for its layer or turkey programs. As described below, all of the NRSP-8 species groups employ common genomics technologies and often have interest in common genes and even common mutations that cause similar traits. The ability of all species groups to "share notes" within the NRSP-8 structure is an enormous advantage.
Another indication of the broad scope of NRSP-8 can be seen in the participation of researchers in the PAG conferences held jointly with the annual NRSP-8 meeting. Annually, ca. 450 animal genome scientists participate. While the breakdown specifically within the animal science group is not available, ca. one-third of all PAG participants are international scientists, testifying to the global scope of NRSP-8. Several Multi-State Research Projects (e.g., NC-1008, -1004, -1037, and -1010) often elect to hold their meetings jointly with the annual NRSP-8 meeting.
b. Continued High Priority. The NRSP-8 mission is closely aligned with the first objective under Challenge 2 of the "2001 Roadmap". In addition, our outcomes contribute towards many other objectives, including germplasm preservation, value-added products, biotechnology, animal behavior and well-being, improved management systems, food safety and biosecurity (Challenge 2), along with aspects of environmental stewardship (Challenge 4) and economic return to agricultural producers (Challenge 5). In the "2006 Update to the Roadmap", NRSP-8-based infrastructure remains fundamental to all objectives within Challenge Area 7, "We can develop new and more competitive animal production practices and products and new uses for animals," in addition to contributing to specific objectives within Challenge Area 1 (eliminate food-borne illnesses and agro-security), Challenge Area 2 (develop more environmentally friendly crop and livestock production systems) and Challenge Area 3 (improve the economic return to agricultural producers).
A much more detailed discussion of the importance of agricultural animal genomics than can be provided here is found within the "Blueprint." This report describes "animal agriculture poised at the threshold of the genomic revolution" and cites studies estimating a 40-50% increase in world demand for meat and dairy products over the next two decades. The Blueprint also points out that "a redirection of the traditional "reductionism science" approach to a "systems biology" approach is required." In the area of Infrastructure, the Blueprint priorities include "Genomic tools to connect genotype to phenotype", "National, comprehensive databases" along with "statistical and bioinformatics tools," "Genetic resources such as centralized animal populations that are deeply phenotyped," and "Education and training." The first three of these are directly aligned with the objectives of this renewal, and NRSP-8 contributes specifically to the final objective through our many communications activities (web sites, email discussion groups, meetings, newsletters, support for graduate and undergraduate student travel to meetings, etc.).
Over the prior 5-year period, NRSP-8 has seen the realization of goals that were initially deemed beyond reach when we began in 1993, among them draft sequences of the bovine, chicken and equine genomes with that of the swine genome nearing completion and others in the planning/proposal stage. It is essential to realize that "completion" of a genome sequence is not the beginning of the end, but rather the end of the beginning. This is certainly evident in the area of human genomics, wherein even though a "finished" quality genome sequence is available, today, human genomics research is more active, vibrant and successful than ever before. Specific reasons for this include:
1. The sequence is a tool for future research rather than an end in itself. Sequence knowledge opens up the opportunity to query the genotypic diversity of a species (e.g., SNP analysis) and to correlate that with phenotypic diversity that is important for traits of economic value to agricultural producers. It also enables new functional genomics technology (transcription profiling, proteomic profiling, high throughput mutagenesis in some species, and the use of next generation sequencers to "re-sequence" diverse or variant individuals).
2. It is increasingly clear that one sequence, even accompanied by extensive SNP typing of many lines and individuals, fails to reasonably encompass the genetic diversity of a species. Thus, we can expect the need to obtain multiple sequences from various lines and breed types per species. Fortunately, new sequencing technologies are being developed that make this a realistic goal.
3. There also remain many species of agricultural importance (e.g., turkey, aquaculture species) that lack a sequenced genome. Comparative genomics using the sequence of a closely related species or extensive EST sequencing provide partial substitutes, and importantly, the reductions in sequencing costs noted above will make it more efficient to fully sequence these genomes in the future.
4. The existing draft sequences, while an enormous advance, necessarily possess gaps and long-range alignment errors for a variety of reasons. This is readily apparent from analysis of several "finished" quality sequences of small regions e.g., the major histocompatibility regions of several species and an entire chicken microchromosome (GGA 28). Thus, there remains a great deal of basic sequencing work necessary, both for the species with sequenced genomes and also for those lacking draft sequences.
In summary, there remains much to accomplish in animal genomics, and we are at a great advantage to do so because of all the knowledge, technology and data generated during the past history of NRSP-8. The complexity of the systems biology era requires new tools and modes of thinking and NRSP-8 has a strong history in stimulating and facilitating both; we expect the project to continue in its forward-thinking fashion. The real excitement of the next five years will derive from our increasing ability to specifically link phenotypes, including quantitative trait loci, to realistic molecular explanations, opening the possibility of both new breeding strategies and biotechnological advances. The mission of NRSP-8 to enhance the infrastructure for agricultural animal genomics remains as important and relevant as ever, if not more so.
Rationale: Priority Established by ESCOP/ESS
NRSP-8 leverages funding to enhance the sharing of genomic resources: tools, reagents, data, animal populations, and bioinformatics. The resulting products support the research community, the commodity groups, industry and government regulatory agencies by providing efficient and accurate tools and information on genome sequences, genetic variation, and the relationship of genotype to phenotype that can be applied in number of ways. Below is a brief summary of the relationship of animal genomics research, for which NRSP-8 provides the necessary infrastructure, to the Updated Challenge Areas (1-4, 6-7) of the National Association of State University and Land Grant Colleges/Experiment Station Committee on Organizational Policy 2006 update to "A Science Roadmap for Agriculture".
Challenge 1. We can ensure food safety and health through agricultural and food systems. A major promise of genomics is that it can lead to (1) healthier and more disease resistant animals that reduce or eliminate food-borne illnesses, (2) animal products with improved nutritional value that promote better human health, and (3) the ability to trace individual animals and their products, which would provide another means for the USDA National Animal Identification System for animal tracing and help ensure biosecurity.
Challenge 2. We can provide the information and knowledge needed to further improve environmental stewardship. As stated, "Genome technologies also offer new opportunities to develop precision management systems to optimize the production environment based on an animal's genotype." A corollary of this goal is the opportunity to reduce the amount of waste generated by animals, which will promote environment-friendly production systems.
Challenge 3. We can improve the economic return to agricultural producers. Superior animals developed in part through genomics enhance the economic return to producers. They improve efficiency by minimizing loss to poor health or mortality, reduce the need for vaccination and other disease control measures, maximize production traits, and minimize the production of waste products, which allows for sustainable production systems and protection of the environment.
Challenge 4. We can strengthen our communities and families. Productions systems that maximize economic return and sustainability promote communities that have a higher standard of living, are healthier and more stable, and help preserve the environment.
Challenge 6. We can lessen the risks of local and global climatic change on food, fiber, and fuel production. A better understanding of how environmental factors such as climate change can influence production and health traits will allow for the generation of elite animals adapted to these new environmental conditions, helping to maintain food and fiber production.
Challenge 7. We can develop new and more competitive animal production practices and products and new uses for animals. The essence of NRSP-8 is to address this challenge. By understanding how genotype and genetic variation influences phenotype and phenotypic variation, we can address all the major goals including (1) Develop innovative technologies for reducing the impact of animal agriculture on the environment, (2) Enhance the value of food and other animal products for both the producer and consumer by using conventional and newly developed technologies that are socially and ethically acceptable, (3) Develop new and enhanced technologies for the improved efficiency and welfare of animals that are processed for food, and (4) Improve conventional technologies as well as developing new technologies to improve the efficiency of animal production.
Rationale: Relevance to stakeholders
A. Stakeholders. The membership constitutes the primary group benefiting from activities although non-members, and in fact, the global scientific community benefit. Obviously, genotype (the genome) is of critical consideration for many disciplines of animal science (physiology, behavior, nutrition, etc.) whose researchers benefit from NRSP-8 supported resources and knowledge. Members participate in governance but all interested parties can have input. One mechanism is via the NRSP-8 supported ANimal GENe MAPpers internet group (ANGENMAP, 1515 members 2/1/08, http://www.animalgenome.org). ANGENMAP hosts numerous opportunities for input. -- International scientists are an important stakeholder group. About one-third of the 450 PAG animal scientist-attendees and one-third to one-half of ANGENMAP members are international. International input also derives from participants of the 2006 US-EC Livestock Genomics Symposium convened by the US-EC Joint Task Force on Biotechnology. -- Commercial breeders, producers, and other entities that rely on agricultural animals constitute a critical stakeholder group. Each NRSP-8 species committee incorporates industry representatives that participate in governance. Industry scientists and leaders attend PAG, utilize ANGENMAP, receive newsletters and employ genomic tools/data deriving from NRSP-8-supported infrastructure. An example of NRSP-8 stakeholder synergy: the poultry industry, USDA-ARS, NRSP-8, and US/international scientists formed a consortium to conduct high throughput SNP-typing of chicken industrial and research populations, creating critical mass to make the project attractive to the commercial distributor of the technology (Illumina Corp.). -- US federal agencies are stakeholders, as APHIS and other regulatory entities find value in, or unique niches for, genomic tools. One example: the USDA National Animal Identification System for animal tracing to promote/ensure food safety. The ability to track individual animals or animal products by genetic markers will only grow in demand. -- The general public constitutes the ultimate stakeholder group for the efforts of NRSP-8. The public pays the bills (via taxes, food costs) and consumes the products of animal agriculture and is meant to be the beneficiary of genetic improvement in the form of a safe, nutritious food supply, at reasonable cost and with minimal environmental impact. Further, the publics communication systems (newspapers, magazines, radio, internet) utilizes NRSP-8-generated materials (websites, newsletters, research articles) as well as the knowledge of species coordinators and member researchers who engage in education/training, interviews, meetings/workshops to provide objective science-based information in regard to animal genomics and agriculture.
B. Stakeholder Involvement. The "Blueprint details opportunities including the annual PAG/NRSP-8 conferences, Allerton Conferences (1990, 1996, 2002), a National Academy of Sciences public workshop, "Exploring Horizons for Domestic Animal Genomics" (2002), and a 2004 USDA-ARS-CSREES Animal Genomics Workshop (at the behest of the Interagency Working Group on Domestic Animal Genomics chartered in 2002 by the U.S. National Science and Technology Council). In 2006, the USDA-ARS and CSREES conducted a joint workshop in the area of animal production and well-being in which animal genomics was a major topic (http://www.ars.usda.gov/research/programs/programs.htm?np_code=101&docid=13166). -- Communication at the individual, commodity, and national levels greatly facilitates feedback and, as necessary, redirection of resources to support stakeholder needs and ensure quality outputs. NRSP-8 addresses the needs of stakeholders by providing the resources, community, and visibility to allow the leveraging of limited resources in support of the Blueprint pillars (Infrastructure, Discovery Science, Science to Practice).
C. Renewal Justification. There is continued need for, and relevance of, NRSP-8 for US scientists who depend on NRSP-8 initiatives and resources. -- No other public or private program can provide the unique services and infrastructure. As the demand for animals and animal products continues to grow, it is essential that the US have a visible program to maintain its global competitive advantage. -- It is clear from biomedical research that the connection between the genome and phenotype is complex. Consequently, a wide group of scientists with diverse skills and expertise with access to high throughput genomic tools and bioinformatics is required to work together to achieve an understanding of this connection that can generate practical results of value for animal agriculture and human health. Noteworthy is the recent designation by NIH of the chicken as a model organism (http://www.nih.gov/science/models/gallus). The NRSP-8 derived value of supporting genome research in our designated animal species will undoubtedly continue to have far-reaching impact on scientific endeavors for the betterment of society. -- As described earlier, genomics technology and the requisite animal populations are costly and often only available at a few specialized sites. Furthermore, technologies evolve at remarkable pace and financial/access constraints make it an imperative to share in the expense of genomic tools and reagents, animal populations, bioinformatics tools and to pool our scientific expertise. Renewal is further supported by the significant impact NRSP-8 has had on stakeholders at all levels. The tools, resources, information, and collaborations attributed entirely or in part to NRSP-8 support have led to a number of important advances and discoveries, see Attach. 1 2003-08 Accomplishments, Attach. 3 Species Genomics Progress. Key examples listed under the main headings designated by the "Blueprint" include:
a. Infrastructure. The majority of contributions fall within Infrastructure. Genome Maps-medium to high-density genetic maps are available for all species. Physical maps derived from BAC clones or RH panels exist for the majority of the species and their integration has enabled the development of comparative maps. Genome Sequences-a major advance has been the release of sequences for chicken, cattle, and horse with pig expected shortly and several fish species in the planning stages. This achievement was facilitated and hastened by the existence of genome maps and other genomic resources. Databases-national and centralized collections of information have been maintained that aid scientists. Communication-while difficult to quantify, it cannot be understated that this project has enhanced both the understanding and consideration of genomics technology. This has allowed companies and other stakeholders to better determine and employ resources for application.
b. Discovery Science. Identification of Genes or QTL Influencing Production Traits-genetic markers, e.g., microsatellites and SNPs, and other genomic resources have led to a large number of studies that relate specific genes or genomic regions to the control of growth, reproductive, health, and other traits of academic and industrial relevance. Biological Pathways-using functional genomic tools, a number of genes and pathways have been implicated that influence traits of interest.
c. Science to Practice. Marker-assisted Selection-genes or genetic markers that show consistent associations to specific traits have been incorporated into commercial breeding programs. Genetic Tools-in many species genetic (marker) tests are being used by the industry to improve animals. Animal Tracing-a very visible example of the power of genomics was the ability to rapidly identify the origin of a cow with BSE. Biodiversity-using a chicken SNP panel, commercial poultry breeders now know how much genetic diversity exists within and among elite lines and for the available world-wide commercial germplasm.
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