NRSP_TEMP281: National Animal Genome Research Program
Statement of Issues and Justification
Prerequisite Criteria: Mission
INTRODUCTIONThe NRSP-8 National Animal Genome Research Support Program has played a major role in enabling genomic discoveries in livestock animals and aquaculture species. As outlined in the Blueprint for USDA Efforts in Agricultural Animal Genomics 2008-2017, infrastructure provides the critical foundation upon which genomics-oriented discovery science can be channeled into substantial advances in agricultural practices. Infrastructure, as defined by the Blueprint, includes genomic tools (e.g., maps, genome assemblies), integrative bioinformatics tools and databases, genetic resource populations, and education and training of students, scientists, and the public. The mission of NRSP-8 focuses on providing support for these crucial infrastructure components. Developed infrastructure is, in turn, used to leverage more substantial funding support for livestock genomics research from a variety of public and private sources. As detailed in the Accomplishments section, NRSP-8 has been highly successful in the previous period in enabling substantial advances in animal genomics and facilitating a broad array of research activities of importance to its component species groups. This success and the rapid advance of genomic technologies emphasize the need for continued NRSP-8 infrastructure support.
The advent of next-generation sequencing (NGS) technologies, and the associated exponential decreases in sequencing costs and increases in throughput, have produced seismic shifts in approaches towards, and the scope of, animal genomics research. For example, while production of high-quality reference genomes for agricultural animals remains a substantial undertaking, sequencing costs are now outweighed by the infrastructure needed to assemble hundreds of millions of multi-platform reads, annotate genes, genome features, and nucleotide variants, and curate this information in a manner accessible to stakeholders. Additionally, as whole genome sequences become available for most target species, NGS makes broad re-sequencing efforts a viable approach for characterizing variation in breeds and strains and linking this variation to economically-relevant phenotypes. Whereas reference genome assemblies mostly were generated at large sequencing centers, NGS has democratized sequencing such that most universities and many companies can now use it to study their own populations of interest. These changing strategies are already generating enormous datasets that can quickly overcome the informatics resources of an individuals lab or even small species groups. These new challenges are reflected in our updated objectives for this renewal, as briefly outlined below and expanded on in the Implementation section.
Our first objective is to advance the status of reference genomes for all species, including basic annotation of worldwide genetic variation, by broad sequencing among different lines and breeds of animals. The NRSP-8 community, organized around species groups, the AnGenMap list- server, and NRSP-8 meetings in conjunction with the annual Plant and Animal Genome Conference (PAG), provides the core infrastructure and leadership necessary for organizing these efforts, including sharing of DNA resources, collaborative use of computational power, and community-based annotation.
Our second objective is to develop strategies to identify and exploit genes and allelic variations that contribute to economically relevant phenotypes and traits, in part through improving functional annotation of the genomes of our species. The tremendous power of genome-wide variant analysis is leading to the identification of markers linked to important production traits in agricultural animal species. These analyses also suggest the involvement of candidate genes, whose functions are often unknown in the studied species. NRSP-8 support is critical to developing powerful functional -omic strategies, from improved annotation to proteomic and metabolomic assays to knock-out/down approaches.
Our third objective is to facilitate analysis, curation, storage, distribution and application of the enormous datasets now being generated by NGS and related technologies with regard to our target species. This bioinformatic capacity is a critical component of infrastructure support enabled by NRSP-8. NRSP-8-supported approaches in this area include continued expansion of the tools and capabilities of the bioinformatics coordination program (http://www.animalgenome.org/), development of community-wide pipelines and portals for variant analysis and curation, training of students, scientists, and stakeholders in high-throughput data analysis, and development of collaborative platforms that facilitate species-group level access to timely genomic data.
Across all objectives of this renewal, the NRSP-8 proposes to continue providing enabling technologies and support activities, and to disseminate data/genetic material otherwise sorely lacking across the animal genomics community. The organizational structure of NRSP-8 serves to bring together domestic scientists within a given livestock/aquaculture group, and facilitate rapid transfer of successful approaches to commercial national and international stakeholders
Prerequisite Criteria: How does this NRSP pertain as a national issue?
A. National Scope. The membership of the NRSP-8 encompasses scientists from the dairy and beef cattle, poultry, equine, sheep, goat, swine, and aquaculture sectors, spread through and impacting agriculture within every state and region of the U.S. The 2010 document A Science Roadmap for Food and Agriculture contains seven grand challenges. While animal genomics research directly or indirectly can be related to each challenge, Grand Challenge 1 - We must enhance the sustainability, competitiveness, and profitability of U.S. food and agricultural systems - directly pertains to NRSP-8 infrastructure support functions. Needed approaches to meet Grand Challenge 1 include Enhance animal productivity by maximizing their genome capacities and developing new animal breeds and stocks&. Animal genomics also has clear national-level roles to play in mitigating climate change impacts (Challenge 2), ensuring a safe, secure, and stable food supply (Challenge 4), and improving human health and nutrition (Challenge 5) through genome-directed selection of breeds and lines that produce food products in a manner meeting national environmental and nutritional needs. The applicability of animal genomic research (and its support via NRSP-8) to a wide array of national issues and animal production needs is reflected both in recent USDA-NIFA proposal requests, which often incorporate a genomics component, and in the diverse applications of the genomic techniques employed by NRSP-8-affiliated researchers. These projects range from nutritional genomics to comparative immunology to marker-assisted breeding, but often share the same core genomic technologies and needs for bioinformatics support. For example, a program developed originally for poultry data analysis in Texas may be readily adapted by researchers working with striped bass in North Carolina.Another indication of the broad scope of NRSP-8 can be seen in the participation in and utilization of NRSP-supported forums, tools, and conferences. The AnGenMap discussion server has 2,242 members around the world. The QTLdb program, developed by the NRSP-8 Bioinformatics Coordination Project team, has been cited in over 150 peer-reviewed publications. Similarly, the PAG conferences are held jointly with the annual NRSP-8 meeting, with 651 animal genome scientists participating in this international meeting in 2012. The chance to compare notes with colleagues throughout the genomics community and to access the most recent developments from genomics industry representatives has been critical for much of the past progress outlined under Accomplishments.
B.Continued Need. As detailed above, the NRSP-8 mission is closely aligned with the challenges described in the recent 2010 Science Roadmap. These challenges for food production are long-term in nature and are heightened by rising world populations and environmental obstacles such as climate change. As animal genomic tools and technologies are increasingly integrated into the breeding and production practices of a wide array of species, the need for national genomics infrastructure support (as provided by NRSP-8) is only expected to increase. Also, while genomics has been applied primarily to breeding and selection, a key deliverable is more biological information on traits.
Whole genome sequences from several species groups were finished and/or refined in the last 5 years, while sequencing was initiated and nears completion in several others. The focus of the proposed renewal turns, therefore, from the structural assembly of primary reference sequences to the capture and utilization of trait-associated genome variation through a variety of approaches. These new approaches are based on having the reference assembly in hand and therefore depend on the quality of the initial reference sequence. It is difficult to overstate the magnitude of this change, which can be compared to parallel developments in computing and digital communications. When NRSP-8 began in the 1990s, few among us expected we would see complete genome sequences available for our species, and many of our stakeholders found minimal relevance of genomics to their work. Today, many, if not most, breeding companies are routinely obtaining whole genome sequences from production lines and can do so in a matter of weeks or days! This progression marks an exciting era for animal genomics, as diverse phenotypes are connected to genotypes and science translates to practice. However, this transition is also marked by significant, new challenges. These include, among others, development of databases suitable for holding and querying vast amounts of re-sequencing data, and development of tools to facilitate annotation and curation of genome assemblies for small research communities (e.g., aquaculture species). As commercial stakeholders/collaborators increasingly implement genome-enabled animal selection programs, portals for data access and entry of phenotypic information will need to become more sophisticated, and yet more user- friendly. NRSP-8 funding will continue to be needed to address these diverse challenges.
The structure, past success, and established interpersonal relationships of NRSP-8 are tremendous assets in facing the new realities of animal genome sciences. Additionally, the broad participation of members with expertise across species and sub-disciplines (e.g., transcriptomics, SNP mapping, bioinformatics, epigenetics) allows for rapid dissemination of advances in tools and techniques and provides a larger combined base of expertise available to the animal genomics stakeholder community. These aspects of NRSP-8 strongly position it for continued success in its mission to enhance the infrastructure for agricultural animal genomics.
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, 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 a 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 of the National Association of State University and Land Grant Colleges/Experiment Station Committee on Organizational Policy 2010 update to "A Science Roadmap for Food and Agriculture".Grand Challenge 1
We must enhance the sustainability, competitiveness, and profitability of U.S. food and agricultural systems. A key means by which advances in U.S. agricultural production can be made is through selection of animals with superior trait performance (e.g., carcass yield, disease resistance, feed- conversion ratio, robustness, athleticism). Selection of superior genotypes across potentially varied production environments is greatly enhanced by integrating genomic data with relevant phenotypes and biological information.
Grand Challenge 2
We must adapt to and mitigate the impacts of climate change on food, feed, fiber, and fuel systems in the United States. Genome-enabled selection practices are increasingly able to take into account the effect of genotype on the ability of an animal to utilize and assimilate different diets and different downstream impacts on the environment. Cross-disciplinary research in nutrition and genomics promises tailored diets that most effectively utilize genetic growth potential while minimizing environmental impact. Additionally, genomics can enhance selection of animals better adapted for changing climatic conditions.
Grand Challenge 3
We must support energy security and the development of the bioeconomy from renewable natural resources in the United States. As sustainability and energy costs become increasingly important factors in the success of animal agriculture, incorporating these complex factors into breeding and management strategies will require the power of genomic selection and a much-improved understanding of gene function. Grand Challenge 4
We must play a global leadership role to ensure a safe, secure, and abundant food supply for the United States and the world. Genomics can enhance the safety of the food supply through animal identity and traceability systems based on molecular markers. Additionally, genomics allows rapid selection of lines of livestock resistant to infection, increasing animal welfare while optimizing productivity. Animal genomics research can additionally target other production bottlenecks, such as maturation times and fecundity, to enhance productivity and nutritional value.
Grand Challenge 5
We must improve human health, nutrition, and wellness of the U.S. population. Healthy, low-priced animal protein choices are the result of a vigorous and profitable animal agriculture industry. Genome-based enhancement of the beneficial nutritional profiles of livestock can lead to healthier dietary options and improved human health.
Grand Challenge 6
We must heighten environmental stewardship through the development of sustainable management practices. Sustainable management includes efficient livestock utilization of nutrients, water, and space with high survival and minimal environmental impact. Selection of animals best suited for production in a given environment via genomic technologies (precision management systems) optimizes sustainability in agriculture.
Grand Challenge 7
We must strengthen individual, family, and community development and resilience. A profitable and growing agricultural sector leads to strong farm families and farm communities. Agricultural animal genomics is focused on enhancing animal improvement programs to lower production costs and increase throughput and yields, thereby increasing profitability. At the same time, these genomic technologies can add aspects of sustainability and biosecurity to production practices, leading to long-term market stability.
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 in parallel. Obviously, genotype (the genome) is of critical consideration for many disciplines of animal science (e.g., physiology, behavior, nutrition) 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 AnGenMap (http://www.animalgenome.org), which allows for essentially a daily conversation among its 2200+ members, including many in the stakeholder community. International scientists are another important stakeholder group. Approximately one-third of the 651 PAG animal scientist- attendees and one-third to one-half of AnGenMap members are international. Commercial breeders, producers, and other entities that rely on agricultural animals constitute another critical stakeholder group. Each NRSP-8 species committee incorporates industry representatives that participate in governance, but many additional industry scientists and leaders attend PAG, utilize AnGenMap, receive newsletters and employ genomic tools/data deriving from NRSP-8- supported infrastructure. The general public constitutes the ultimate stakeholder group for the efforts of NRSP-8. The public pays the bills (via taxes, food costs, etc.) and consume the products of animal agriculture; it is meant to be the beneficiary of genetic improvement in the form of a safe, nutritious, high quality food supply, at reasonable cost and with minimal environmental impact. Further, the publics communication systems (e.g., newspapers, magazines, radio, and internet) utilize NRSP-8-generated materials (e.g., websites, newsletters, research articles) as well as the knowledge of species coordinators and member researchers who engage in education/training, interviews, and meetings/workshops to provide objective science- based information in regard to animal genomics and agriculture.B. Stakeholder Involvement. A few examples of stakeholder synergy in the recent period may help to illustrate the community-building impact of NRSP-8. First, the dairy (Holstein) industry, USDA-ARS, NSRP-8 and other U.S./international scientists formed a highly successful collaboration to utilize the BovineSNP50 genotyping chip for implementation of whole genome selection. Second, the PRRS Host Genetics Consortium brought together swine breeding companies, the National Pork Board, USDA-ARS, NRSP-8 and other U.S. scientists to identify genetic mechanisms controlling host response to PRRS virus infection in nursery pigs. Third, the Equine Genetic Diversity Consortium, consisting of scientists from 25 institutions worldwide, is analyzing a 50K SNP dataset from 36 breeds for signatures of selection, intra- and inter-breed diversity. While these are just a few examples, as noted below (Integration and Documentation section), all the coordinators have engaged in species-specific and, in some cases, cross-species interactions with academic and industry stakeholder groups.
While face-to-face interactions at PAG and other venues remain important, increasingly stakeholder interaction is through Internet resources. This is why the AnGenMap on-line discussion group is so important to NRSP-8 (detailed below in Outreach). Furthermore, each species group has its own species-specific website, with links to maps, databases, newsletters, resources and community links, and all of these are combined at the NRSP-8 Bioinformatics Coordination Site (www.animalgenome.org). Stakeholders increasingly utilize NRSP-8 bioinformatic resources alongside academic researchers, helping to ensure the accuracy of sequence assemblies, the accessibility of newly developed programs, and the real-world relevance of project directions. 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 U.S. scientists and stakeholders who depend on NRSP-8 initiatives and resources. No other public or private program can provide these unique services and infrastructure. As the demand for animals and animal products continues to grow, it is essential that the U.S. have a visible program to maintain its global competitive advantage. It is clear 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 must work together to achieve an understanding of this connection to generate practical results of value for animal agriculture and human health. 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. Animal genomics faces a challenge today that parallels that faced by medical genetics. It is likely that many young people in the U.S. today will have their own genome sequenced. How can that immense amount of information be stored, analyzed, communicated and interpreted in a way that positively impacts his or her health and lifespan? What collateral information and infrastructure will be needed for these sequences to have real value? Similarly, how will animal producers and scientists (and ultimately society) be able to benefit from genomic advances? These technologies evolve at a remarkable pace, and it is imperative to share genomics tools and reagents, animal populations, and bioinformatics tools, and to pool our scientific expertise. Renewal is further supported by the significant impact that 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 the Accomplishments 2008-2012 attachment).
The most obvious and important example of this progress has been obtaining, refining, and using the reference genome sequence assemblies for the majority of our target species. The reference assemblies have enabled other approaches aimed at gaining a full appreciation of animal genetic diversity within many of our species, the use of genomic selection in animal breeding, better implementation of new transcriptomic and proteomic approaches, and a reference to which to turn in the analysis of the phenotypic effects of any gene of interest. Still, many challenges remain. Stakeholders depend on the reference assemblies in the way we previously depended on encyclopedias and dictionaries. At the moment, they frequently find missing and/or incorrectly assembled genes and regulatory elements. The reality is that their best access to the genome may be out-of-date or difficult to interpret. The overarching challenge remains the complexity of genome sequences and data, and the difficulty in connecting those data to the equally complex outcome the phenotype. It is difficult to envision exactly how we can develop a full appreciation of the functional connections between DNA sequence and, for example, feed conversion efficiency or disease resistance. However, many difficult-to-envision concepts and dreams have been realized by research supported by NRSP-8 in the past, and we can confidently predict that this will continue to occur in its next cycle.
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