Page 1

United States

Department of

Agriculture

Agricultural

Research

Service

Cooperative

State Research,

Education, and

Extension Service

September 2007

Blueprint for USDA

Efforts in Agricultural

Animal Genomics

2008­–2017

Blueprint for USDA

Efforts in Agricultural

Animal Genomics

2008­–2017

United States

Department of

Agriculture

Agricultural

Research

Service

Cooperative

State Research,

Education, and

Extension Service

September 2007

USDA Animal Genomics Strategic Planning

Task Force

Abstract

USDAAnimal Genomics Strategic Planning

Task Force. 2007. Blueprint for USDA Efforts

in Agricultural Animal Genomics 2008–2017.

U.S. Department of Agriculture, Agricultural

Research Service and Cooperative State

Research, Education, and Extension Service,

Washington, DC.

Following the recommendation of the

National Science and Technology Council’s

Interagency Working Group on Animal

Genomics, a task force was established

in January 2006 to develop a blueprint

for USDA efforts in agricultural animal

genomics. This task force of Agricultural

Research Service (ARS), Cooperative State

Research, Education, and Extension Service

(CSREES), and university scientists and

administrators developed a “Blueprint” for

future research, education, and extension

efforts in agricultural animal genomics,

based on a vast array of stakeholder input.

The Blueprint is designed as a pyramid, with

“Science to Practice” at the top, supported by

fundamental and mission-oriented research in

“Discovery Science,” and is based on a solid

foundation of “Infrastructure.” The Blueprint

will guide activities in this critical area of

science over the coming decade.

Keywords: animal genomics, animal

genomes, food animal, animal production,

animal selection, genome mapping,

bioinformatics, comparative genomics,

functional genomics, genetic selection,

systems biology.

Mention of trade names or commercial

products in this report is solely for the

purpose of providing specific information

and does not imply recommendation or

endorsement by the U.S. Department of

Agriculture.

To ensure timely distribution, this report was

reproduced essentially as supplied by the

authors. It received no publication editing and

design.

While supplies last, single copies of this

publication may be obtained at no cost from

Ronnie D. Green, USDA-ARS, National

Program Leader, Animal Production, 5601

Sunnyside Avenue, Room 4-2104, Beltsville,

MD 20705-5148; or by e-mail at ronnie.green@

ars.usda.gov.

Copies of this publication may be purchased

in various formats (microfiche, photocopy,

CD, print on demand) from the National

Technical Information Service, 5285 Port

Royal Road, Springfield, VA 22161, (800) 553-

6847, www.ntis.gov.

The U.S. Department of Agriculture (USDA)

prohibits discrimination in all its programs

and activities on the basis of race, color,

national origin, age, disability, and where

applicable, sex, marital status, familial status,

parental status, religion, sexual orientation,

genetic information, political beliefs, reprisal,

or because all or part of an individual’s

income is derived from any public assistance

program. (Not all prohibited bases apply to

all programs.) Persons with disabilities who

require alternative means for communication

of program information (Braille, large print,

audiotape, etc.) should contact USDA’s

TARGET Center at (202) 720-2600 (voice and

TDD). To file a complaint of discrimination,

write to USDA, Director, Office of Civil

Rights, 1400 Independence Avenue, S.W.,

Washington, D.C. 20250-9410, or call (800)

795-3272 (voice) or (202) 720-6382 (TDD).

USDA is an equal opportunity provider and

employer.

September 2007

Contents

Executive Summary...........................................................................1

Introduction........................................................................................4

Stakeholder Input...............................................................................5

Science to Practice..............................................................................7

Discovery Science...............................................................................9

Infrastructure....................................................................................12

Conclusion ........................................................................................14

About the Task Force.......................................................................16

References..........................................................................................17

Appendix I ........................................................................................19

Appendix II.......................................................................................20

Discovery Science

Science to Practice

Infrastructure

Animal Identity/Traceability

Precision Management Systems

Precision Mating Systems

Genome-Enabled Animal Selection

Systems Biology

Host:Pathogen Interactions

Functional Genomics

Gene Discovery

Education & Training

Animal Resource Populations

Databases & Bioinformatics

Genomic Tools

1

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

E

xEcutivE

S

ummary

Animal improvement programs have

greatly increased the ability of animal

agriculture to provide high quality, low

cost and safe animal products to the

American consumer. A large part of this

change is a result of investments made

by USDA in quantitative animal genetics

and animal molecular biology research

as well as the ability of private industry

to rapidly adopt these new technologies.

Investments in genomic technology, from

gene discovery to sequenced genomes,

and state-of-the-art technology developed

by the biomedical research community,

have animal agriculture poised at the

threshold of the genomic revolution.

Although quantitative geneticists have

made tremendous progress in improving

the efficiency of meat, milk, and egg

production, there is still a significant

need for increased production efficiency.

For example, if Americans are to fully

meet the 2005 Dietary Guidelines for

Americans, U.S. dairy producers will

need to increase annual production of

milk and milk products (especially fat-

free or low-fat dairy products) by an

estimated 65% (Buzby et. al., 2006). In

addition, by 2020-2030 world demand for

meat and dairy products is expected to

increase 40-50% (Rosegrant et. al., 2001;

FAO, 2002), which will stimulate the

competitiveness of American food animal

products. Genome-enabled technologies

will also lead to improvements in product

quality, including nutrient-fortified lean

meat, milk, and eggs to satisfy increasing

demand for healthier food from aging or

obese consumers. Animal genomics will

also provide the ability to understand and

improve genetic traits that were difficult

to measure with quantitative genetics

approaches (e.g., disease resistance,

animal well-being, feed efficiency, and

product quality) and will lead to enhanced

functionality and well-being of animals

in environmentally neutral production

systems. In the near future, genome-

enabled technologies will be used to trace

animals and animal products throughout

the food production chain resulting in

enhanced biosecurity as well as increased

food safety and consumer confidence.

Thus, with additional USDA-supported

efforts, new genomic technologies will

be available to livestock, poultry, and

aquaculture producers to improve the

efficiency, sustainability, biosecurity, and

social acceptance of agricultural animal

production.

To meet these national needs, a blueprint

for future research, education, and

extension efforts in agricultural animal

genomics has been developed by a task

force of ARS, CSREES, and university

scientists and administrators. The

Blueprint is built on a vast array of

stakeholder input and is designed as

a pyramid, with Science to Practice at

the top supported by fundamental and

mission oriented research in Discovery

Science, and is based on a solid foundation

of Infrastructure.

The goals and recommendations of

the Blueprint are consistent with the

President’s American Competitiveness

Initiative (2006) which stresses the

importance of targeting “..investments

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Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

toward the development of deeper

understanding of complex biological

systems..”. The Blueprint is consistent

with the 2005-2010 USDA Strategic

Plan, including its Goal 1 (Enhance

International Competitiveness of

American Agriculture), Goal 2 (Enhance

the Competitiveness and Sustainability

of Rural and Farm Economies), Goal 4

(Enhance Protection and Safety of the

Nation’s Agriculture and Food Supply),

and Goal 5 (Improve the Nation’s

Nutrition and Health). Appendix I

provides additional information regarding

how the Blueprint aligns with these USDA

Goals.

Science to Practice Priorities:

Quantitative genetics has been used

for many years in selecting animals for

improved production (e.g., growth, yield,

efficiency) and has achieved remarkable

results. The addition of animal genomic

technology to quantitative genetics

programs has the potential to lead to more

accurate and rapid animal improvement,

especially for phenotypic traits that are

difficult to measure (e.g. disease resistance,

animal well-being, feed efficiency, product

quality). Genomic technologies also offer

new opportunities to develop precision

management systems to optimize the

production environment based on an

animal’s genotype. In the short-term,

research, education, and extension efforts

in animal genomics are expected to deliver

the following genome-based technologies

to animal producers:

1) Whole-genome-enabled animal

selection.

2) Prediction of genetic merit of

individual animals from genome-

based data combined with

phenotypes.

3) Integration of genomic data into large

scale genetic evaluation programs

and the use of genomic information to

design precision mating systems.

4) Precision management systems to

optimize animal production, health,

and well-being.

5) Genomic capabilities that enable

parentage and identity verification

(traceability).

Discovery Science: Critical gaps in

our understanding of gene structure

and function in animals must be filled

before animal genomics technologies

can be successfully applied to animal

industries. Agricultural animals form a

unique resource to study the fundamental

underlying biological mechanisms of gene

structure and function, regulation of gene

expression, and the genetic contribution

to phenotypic variation because, unlike

humans, animals have been artificially

selected to express or repress specific

traits. Advances in discovery science will

require interdisciplinary teams of scientists

that address complex agricultural issues

with state-of-the-art equipment and

approaches that include systems biology

and comparative genomics. The following

are priorities in discovery science for

animal genomics:

1) Identify genes and gene products

that regulate important traits in

agricultural animals such as disease

resistance, animal well-being, feed

efficiency, and product quality.

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

2) Understand mechanisms that regulate

agriculturally relevant genes in a

systems biology framework.

3) Define the mechanisms through which

specific genes and genetic variation

influence phenotypes and phenotypic

variation.

4) Understand the roles and interactions

of host animal and microbial genomes

and environmental influences (e.g.,

animal feed, vaccines) for improving

animal health, well-being, and

production efficiency.

Infrastructure: A solid infrastructure is

needed to support advances in discovery

science. The priorities for a solid

infrastructure are:

1) Genomic tools to connect genotype to

phenotype and elucidate pathways

of complex traits for all agricultural

animal species. These genomic

tools include comprehensive,

high resolution genome maps and

assembled and annotated genomic

sequences.

2) National, comprehensive databases

and the statistical and bioinformatics

tools that integrate genomic,

phenotypic, and experimental

information for each species.

3) Genetic resources such as centralized

animal populations that are deeply

phenotyped as well as repositories for

cell lines, DNA and RNA collections,

and gene expression resources for all

species. The mission of the National

Animal Germplasm Program should

be broadened to become a coordinated

national repository for genomic

DNA, appropriate DNA libraries, and

specialized cell lines.

4) Education and training of students,

scientists, and the public on

genome-enabled animal sciences

and opportunities that help prepare

the next generation of scientists.

Particular emphasis should be placed

on integrating quantitative genetics,

genomics, immunology, nutrition,

physiology, biochemistry, cell biology,

developmental biology, ecology,

engineering, physics, mathematics,

and computer science with

development of scientists who have a

keen appreciation for, and knowledge

of, animal production systems.

Additional emphasis on extension

and outreach will enable and facilitate

effective translation of genomics

research and resulting technologies

to the agricultural animal production

sector and the public.

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

i

ntroduction

Agricultural animal research has been

successful in developing technology

and methodologies that have enhanced

production efficiency of the beef, dairy,

swine, poultry, sheep, and aquaculture

industries. Excellent examples of the

changes that have taken place over the

last 50 years are: 1) The dairy industry’s

coupling of genetic selection and

efficacious use of artificial insemination

has more than doubled the annual milk

yield per cow while reducing the size of

the national dairy herd by about 50%; 2)

Genetics, nutrition and other management

changes resulted in a “modern day”

broiler that requires approximately

one-third the time and over a threefold

decrease in the amount of feed consumed

to produce a market-age broiler; and

3) The pounds of feed needed to produce

a pound of pork is estimated to have been

halved. While quantitative geneticists have

been successful in improving production

traits, genomic technology has potential

to lead to more accurate and rapid animal

improvement, especially for phenotypic

traits that are difficult to measure (such

as disease resistance, animal well-being,

feed efficiency, and product quality).

The potential for future improvements

in animal production efficiency, quality

of animal products, animal health and

animal well-being lies in the elucidation

and understanding of interactions of the

various components of animal biology

in concert with all of the parameters of

the production environment. To begin

to fully understand these interactions, a

redirection of the traditional “reductionist

science” approach to a “systems biology”

approach is required. It is also clear that

publicly supported agricultural research

must be focused on enhancing the nutrient

composition of meat, milk, and eggs and

enhancing the functionality and well-

being of animals in environmentally

neutral production systems.

In the past two decades, molecular biology

has changed the face of agricultural

animal research, primarily in the arena of

genomics and the relatively new offshoot

areas of functional genomics, proteomics,

transcriptomics, metabolomics and

metagenomics. Recently, the agricultural

research community has been able to

capitalize on the infrastructure built by

the human genome project (Collins et al.,

2003; International HapMap Consortium,

2005) by sequencing two of the major

agricultural animal genomes, Gallus

domesticus (International Chicken Genome

Consortium, 2004; Wong et al., 2004) and

Bos taurus (Gibbs et al., 2002). The 2006

calendar year marked a major milestone

in the history of agricultural animal

research since annotated draft genome

sequences were completed for chickens

and cattle and sequencing was initiated

for the porcine and equine genomes. We

now have in place a powerful toolbox

for understanding the genetic variation

underlying economically important and

complex phenotypes of agricultural

animals.

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

S

takEholdEr

i

nput

The priorities and recommendations

contained in this Blueprint are based on a

substantial amount of stakeholder input

that was provided to USDA National

Program Staff by scientists, producers,

animal industry and commodity groups,

other federal research agencies, and the

general public.

In 1990, an Allerton Conference entitled

“Mapping Domestic Animal Genomes:

Needs and Opportunities” was hosted

by the University of Illinois while a

Banbury Conference was held at Cold

Spring Harbor on “Mapping Genomes

of Agriculturally Important Animals”.

Participants at these workshops

recommended to USDA that genetic maps

be developed for each of the agriculturally

important species (cattle, swine, poultry,

sheep, and fish).

A second Allerton Conference entitled

“Genetic Analysis of Economically Important

Traits in Livestock” was convened in 1996.

The primary recommendation of the

workshop was a call for building the

research infrastructure necessary to enable

researchers to identify important genes

that control economically important traits

and, eventually, gain an understanding of

the function of individual genes and their

interactions across the genome (Schook,

1997).

In 2002, the National Academy of

Sciences hosted a public workshop

entitled “Exploring Horizons for Domestic

Animal Genomics” (National Academies

Press, 2002). The workshop participants

identified the need to produce high-

coverage, draft genome sequences of some

domestic animal species (cattle, chicken,

swine, dog, and cat) for deposit into the

public domain databases. Furthermore, it

was recognized that there would be a need

to scale up bioinformatics resources to

make effective use of the information that

would result from the genome sequencing

projects. Based upon the experiences of

the National Plant Genome Initiative, it

was also discussed that funding for such

large-scale projects would likely need to

come from a variety of sources, including

the U.S. Federal government, private

industry, and international partners.

In 2002, a third Allerton Conference

entitled “Beyond Livestock Genomics” was

conducted to develop an initial plan for

the full utilization of genomic information

to promote animal health and productivity.

The overarching recommendation from

this workshop was that additional basic

research was needed to identify genomic

mechanisms and novel genes/proteins

in a variety of tissues under a variety of

environmental conditions (Hamernik

et al., 2003). Functional genomics was

recognized as the vehicle for capitalizing

on the investment of obtaining whole

genome sequence information. The need

to increase bioinformatics infrastructure,

teaching, and outreach efforts in animal

genomics was recognized also. To further

define priorities for animal bioinformatics,

an electronic workshop was conducted

in 2002. Priorities for animal genome

database development included: 1) data

repository, 2) tools for genome analysis,

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

3) annotation, 4) practical application

of genomic data, and 5) a biological

framework for DNA sequence (Hamernik

and Adelson, 2003).

An Interagency Working Group (IWG)

on Domestic Animal Genomics was

chartered in September of 2002 by the

U.S. National Science and Technology

Council. The membership of the IWG

included representatives from the

Department of Agriculture (USDA),

Department of Energy (DOE), Food and

Drug Administration (FDA), National

Institutes of Health (NIH), National

Science Foundation (NSF), Office of

Science and Technology Policy (OSTP),

Office of Management and Budget (OMB),

Department of Homeland Security (DHS)

and the U.S. Agency for International

Development (USAID). The IWG

identified the following broad strategic

goals: 1) Bring into place the programmatic

elements needed to advance the study

and understanding of domestic animal

genomes, including large-scale DNA

sequencing; functional characterization

of expressed genes (functional genomics);

tools for data storage, analysis and

visualization (bioinformatics); and

study of similarities among genomes of

different species (comparative genomics);

2) Leverage the national infrastructure

for large-scale DNA sequencing that has

been established for the Human Genome

Project and other vertebrate and model

organism genomes; 3) Advance and utilize

the enabling tools and infrastructure of

functional genomics and bioinformatics

to enhance the understanding not only

of basic science and disease mechanisms,

but also to address critical agricultural

missions, including animal health and

well-being, food safety, and human

nutrition; 4) Ensure that genomics data

are freely available in the public domain

and genomics reagents and resources are

available to the public; 5) Increase the

training opportunities for genomics and

bioinformatics at all levels of education;

and 6) Coordinate and encourage

international cooperation to achieve these

goals.

In early 2004, as the sequencing goals

of the IWG appeared to be within

reach, the IWG charged the USDA with

evaluating how bioinformatics and

functional genomics programs should be

developed further to allow full utilization

of annotated genome sequences and

associated tools. An Animal Genomics

Workshop was convened by USDA

administrators in ARS and CSREES in

2004. The workshop resulted in a list of

priorities in each of these areas for the

“post-sequencing era” for agricultural

animal genomics (Green et al., 2007). A

primary recommendation resulting from

this workshop was that “USDA should

expeditiously develop a coordinated long-

term strategic plan for efforts in agricultural

animal genomics”. Thus, in January 2006

the USDA Undersecretary for Research,

Education, and Economics appointed an

Animal Genomics Strategic Planning Task

Force to develop a Blueprint intended to

guide future decision making and priority

setting by the Department and its relevant

agencies.

7

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Discovery Science

In 2006, the ARS and CSREES conducted a

joint stakeholder workshop in the area of

animal production and well-being where

previous input was further validated by

scientists, producers, and representatives

of animal commodity groups and

animal industries. A summary of the

ARS and CSREES stakeholder workshop

is available at: (http://www.ars.usda.

gov/research/programs/programs.

htm?np_code=101&docid=13166 ).

Additionally, in July 2006, a US-EC

Livestock Genomics Symposium was held

under the auspices of the US-EC Joint Task

Force on Biotechnology. The priorities

identified in this session allowed USDA to

assure that efforts between the European

Commission and U.S. research programs

were complementary in achieving impacts

in agricultural animal genomics and

also identified areas for transatlantic

collaboration (Burfening et. al., 2006).

Input from both of these events was used

in the formulation of the USDA Blueprint.

S

ciEncE to

p

racticE

Application of basic science to improve

animal production practices is the goal

of animal genomics research. In the

short-term, the combined use of genomic

information with existing animal breeding

and animal management programs will

provide immediate impacts, such as more

accurate and accelerated rates of genetic

improvement of breeding stock (especially

for traits that have been traditionally

difficult to measure), animals that are

more adaptable and better suited to

various production environments, and

new genome-based technologies to enable

parentage and identity verification (i.e.,

traceability). Delivery and adoption of

new genome-based technologies will

require integrated activities involving

basic scientists, educators (classroom

and extension specialists), animal

breeding and artificial insemination

organizations, and producers working

together to utilize these technologies. In

the long-term, animal genomics efforts

will lead to efficient and economical

production of human pharmaceutical

proteins in animals, new technologies

for manipulation of gene expression

in animals (i.e., RNA interference,

transgenesis, etc.), and improved methods

for conserving biodiversity and unique

animal germplasm. Because of the existing

widespread use of quantitative genetics

in animal breeding programs in the U.S.

and the rapid rate at which genomic

information is being discovered, the

initial applications of genomics efforts

will be the combined use of genomic

data with quantitative genetics for

animal improvement, management,

and biosecurity. Thus, USDA-supported

research, education, and extension efforts

in animal genomics are expected to deliver

the following genome-based technologies

to livestock producers in the short term:

1) Whole genome enabled animal

selection resulting in a significant

reduction in selection cost and

generation interval. One of the first

and most exciting avenues to explore

is the possibility of using dense single

nucleotide polymorphism (SNP) maps

coupled with haplotype information

8­

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

within species to enable “whole-

genome selection” for traits important

in the overall breeding objective. Such

approaches should accelerate the

rate of genetic improvement, while

simultaneously reducing progeny

testing costs to the animal industries. In

addition, precise genetic improvement

will be obtained because SNP markers

can be used to monitor selection for

more than one trait throughout the

entire genome.

2) Prediction of genetic merit from

genome-based data combined with

phenotypes. In order to fully harness

the power of genomic information

for genetic improvement, a meshing

together of quantitative genetics

theory and platforms with genomic

data will be required. Additionally,

significant research and software

development is required to integrate

all forms of genomic information,

following validation, into large-scale

genetic evaluation systems. A critical

step in the process of moving to

genome-enabled animal improvement

is the development of standardized

systems for recording performance

phenotypes for complex and difficult

to measure traits. This is particularly

true for traits that capture the genetic

variation of animals for adaptation

to their production environments

(stress resistance, behavior, innate

resistance to disease) and for measures

of efficiency of nutrient utilization

(e.g. feed efficiency), amongst others.

A major effort will be required

for these traits to be defined and

parameterized, followed by evaluation

in genetic resource populations to

identify genomic control mechanisms

underpinning observed variation.

3) Integration of genomic data into large

scale genetic evaluation programs

and the use of genomic information

to design precision mating systems.

Not only will genomic information be

of use in prediction of genetic values

for complex traits, the resulting tools

from such approaches will also allow

design of precision mating systems.

More precise information at the

genomic level can be incorporated into

mating system design to minimize

the cumulative effects of inbreeding

from selection and predict matings

that will optimize the use of non-

additive genetic variation for traits

where hybrid vigor is of importance.

Knowledge of epigenetic effects will

also be required to fully capture the

value of this use of genomic data.

4) Precision management systems to

optimize animal production. Genomic

information will also provide the

basis for development of precision

management systems. Knowledge of

an animal’s genotype will allow precise

sorting of animals into the optimal

production environment, resulting

in enhanced animal well-being. For

example, the genotype of some beef

and dairy cattle may be more suited

to pasture-based production systems

rather than confinement systems.

Feeding regimens and preventative

health care programs can also be

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

designed to match an animal’s

genotype and lead to increased

production efficiency, targeted market

endpoints, and new opportunities for

niche markets. The expected amount

of genomic information will require

development of decision support

systems for use in the industries to

implement and manage such genome-

enabled precision management

systems. The ability to precisely control

expression of selected genes (such as

inactivation of the myostatin gene to

increase lean muscle mass) may also

lead to increased production efficiency,

more consistent meat quality, and

healthier animals.

5) Genomic capabilities that enable

parentage and identity verification

(traceability). Development of

high-throughput genotyping

systems that allow for individual

animal identification and parentage

identification will likely have an

immediate impact on all animal

industries. High-throughput SNP

genotyping systems are affordable and

will likely be commercially available

for most agricultural animal species

in the near future. In today’s world,

biosecurity is a major issue due to the

concentration of animal populations

and widespread movement of animals.

Genomic techniques and technology

should be harnessed to provide a

quick, affordable, and foolproof means

of animal identification for traceability

resulting in increased food safety

and consumer confidence in the food

supply.

d

iScovEry

S

ciEncE

Critical gaps in our understanding of

gene structure and function in animals

must be filled before genome-enabled

technologies can be successfully applied

to animal improvement, management,

and biosecurity programs. Rapid progress

in discovering new knowledge related

to animal gene structure and function

will require interdisciplinary teams

of scientists, access to state-of-the-art

equipment, technology, and approaches

that include systems biology and

comparative genomics.

Instead of analyzing individual

components or aspects of the organism,

systems biology incorporates all

biological components and their

interactions. Systems biology will promote

identification and determination of the

function(s) of a complete set of genes and

regulatory elements and will integrate

analysis of DNA sequences, transcriptional

regulation, proteomics, and metabolic

networks and pathways. The ultimate

goal is to understand how genotype

contributes to phenotype and phenotypic

variation. Animal populations that have

been selected for specific phenotypes

and that have been well-characterized at

the molecular and whole animal levels

provide a valuable resource for discovery

research in this area.

Comparative genomics will be an essential

tool to take advantage of knowledge

obtained from species with finished

genome sequences (i.e., human, mouse,

rat) to advance the knowledge of genomes

10

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

from agricultural animals. DNA sequences

that have been highly conserved across

species are likely to have functional

significance, either as genes or as

regulatory elements. Agricultural animals

will play a significant role in revealing

the basic biology of how chromosomes

evolved and how functional elements

within a genome are organized to produce

different phenotypes. Comparative

genomics will also point to specific

targets for understanding and potentially

modulating gene expression. Since it is not

likely that the genomes from all animals of

agricultural importance will be sequenced

in the near future, comparative genomics

will provide an important tool for

extrapolating genetic information between

closely related species (such as chickens

and turkeys or cattle and sheep).

The priorities for advancing discovery

science in the short-term are:

1) Identify genes and gene products

that regulate important traits in

agricultural animals. Previous

research in agricultural animal

genomics has identified a substantial

number of genomic regions harboring

Quantitative Trait Loci (QTL) for a

variety of economically important

traits. Fine-mapping of these QTL

and identification of many more

gene and genic interaction effects for

a wide array of traits of economic

and societal importance are expected

in the near future. Comparative

genomics will be an important tool

to discover genes that are common

across species (and thus are thought to

control important biological processes

conserved throughout evolution) as

well as novel genes within a species

that may give rise to species specificity

and phenotypic variation. In addition,

proteomics and metabolomics

studies will need to be conducted to

discover novel proteins that regulate

agriculturally relevant traits in

agricultural animals.

2) Understand mechanisms that regulate

agriculturally relevant genes in

a systems biology framework.

Although progress has been made in

understanding the mechanisms that

regulate individual genes in isolated

systems (i.e., in isolated cell cultures),

many of the basic mechanisms that

regulate gene expression in the context

of the whole animal still need to be

determined. Expression profiling of

large numbers of genes across diverse

tissues, animal populations, and

environmental conditions using DNA

chips, microarrays, or next-generation

sequencing will identify novel genes

and characterize spatial and temporal

expression of these genes. Additional

technologies to knock out (such as

RNA-interference; RNAi) or knock-in

(i.e., transgenesis with opportunities

for spatial and temporal control of the

transgene) gene expression will need to

be optimized for more efficient use in

animals.

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Discovery Science

3) Define the mechanisms through which

specific genes and genetic variation

influence phenotypes and phenotypic

variation. Discovery science is also

needed to unravel the complexities

of epistatis and the interactions of

genotype by environment and how

they affect phenotype. Development

of clear and standardized descriptions

or ontologies for defining phenotypes

(especially for phenotypes that are

difficult to measure) for animals are

needed. Efficient, systematic, and

comprehensive phenotypic screening

procedures and tools that will permit

comparison among laboratories are

also needed. The identification of

haplotypes within and between breeds

of animals will enhance the mapping of

traits and the ultimate identification of

mutations underlying those traits that

may give rise to phenotypic variation.

4) Understand the role of host

genomes and microbial genomes

to improve animal health and well-

being. Despite efforts to control the

production environment (e.g. housing

systems, feeding systems, thermal

environment), animals are not born

and raised in isolation. The interaction

of host, beneficial and pathogenic

microbes, and environment ultimately

determines whether an animal remains

healthy or is challenged by disease.

Consequently, understanding the

variation in how an animal responds

to various microbes and environments

can have profound influences on the

outcome of the interactions. Current

efforts of most scientists are directed

toward understanding the genetics

or physiology of the host, finding

pathogenicity genes in viruses or

other pathogens, and examining how

animal feeds and environmental

parameters influence the composition

of the microbial community in

the digestive tract. While these

approaches have been successful,

further advances in animal health

and well-being will require a systems

biology approach by interdisciplinary

teams of scientists. State-of-the-art

metagenomics technologies can

be used to understand the genetic

composition of poorly characterized

microbial communities in the rumen

and gastrointestinal tract of animals.

Functional genomics efforts will define

the microbial response in the rumen or

gastrointestinal tract to different hosts

or changes in environmental conditions

such as nutrition, management, or

therapeutics. Future genomics efforts

will allow selection of animals for

superior disease resistance, vaccine

response, or adaptability to various

production environments. In addition,

improved vaccines, diagnostics

and therapeutics can be developed;

producers can devise better precision

feeding systems to improve efficiency

of nutrient utilization and enhance

animal well-being; and use of anti-

microbials and pesticides can be

reduced in agricultural animal

production.

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Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Infrastructure

Discovery Science

i

nfraStructurE

A solid infrastructure is needed to

facilitate advances in discovery science

in animal genomics in a time and cost-

effective manner. Infrastructure refers

to state-of-the-art genomic tools and

resources that are available to the scientific

community as well as a highly trained

and skilled workforce. The infrastructure

needed to advance animal genomics

efforts does not require additional bricks

and mortar. The priorities for a solid

infrastructure in animal genomics are:

1) Genomic tools to connect genotype to

phenotype and elucidate pathways of

complex traits for all animal species

important to agriculture. These

genomic tools include: comprehensive,

high resolution genome maps and

assembled and annotated genomic

sequences.

Genome Maps: Genetic maps are

the basis for identifying genome

regions that affect genes of economic

importance in agricultural animals.

Genetic linkage maps are needed for all

agricultural animal species so that each

species can utilize the most current

selection practices. Linkage maps

for all species must be of sufficient

density so that genomes can be

scanned effectively and efficiently for

economically important loci. Physical

maps are needed so that researchers

can characterize specific regions of the

genome. Maps based on segregation of

markers in irradiated hybrid cell lines

provide the resolution needed to order

markers and genes in very narrow

regions of the genome (less than

100,000 bases apart) and are excellent

resources for developing comparative

maps between species. Whole genome

physical maps are composed of

ordered BAC clones, which contain

large segments of cloned DNA

(100,000-200,000 bases) necessary to

develop markers for use in commercial

animal populations.

Assembled and Annotated Genomic Sequences:

An assembled genome sequence is a

compilation of all of the available DNA

sequence into long contiguous (contigs)

stretches of DNA and assignment of

DNA contigs to specific chromosomes.

Assembled genome sequences provide

insight into the evolutionary processes that

occurred during development of a species;

allow basic studies on the architecture of a

genome; allow characterization of genetic

variation that underlies traits; and provide

information regarding organization of

genes and their impact on expression of

genes in different tissues. An annotated

genome sequence contains information

regarding the gene name, gene structure,

function of the gene product, cellular

location of the gene product, as well as

how this knowledge was determined (i.e.,

literature citation). A finished, annotated

genome sequence should be available for

the most economically important species

(currently these species include: cattle,

chicken, and swine). The target for these

species should be a 10-fold or greater

coverage of the genome. The next tier

of economic importance (for example:

catfish, equine (currently at 6.8X), salmon,

1

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

sheep, tilapia and turkey) should have

a high quality draft genome sequence

(approximately 6X). This level of genome

sequence quality is necessary for accurate

functional genomic studies as well as

comparative analyses. Additional species

(for example: goat, oyster, shrimp, and

trout) should have a low quality draft

genome sequence (approximately 2X).

This level of coverage, coupled with

genetic and physical maps, would advance

the basic biology of these species as well as

allow for limited comparative analyses.

2) National, comprehensive databases

and the statistical and bioinformatics

tools that integrate genomic,

phenotypic, and experimental

information for each species. To

effectively use the resources being

generated from efforts in animal

genomics, there is a need to design,

construct and maintain large

comprehensive databases and the

statistical and bioinformatic tools

that integrate information from these

databases for a variety of applications.

As annotated sequence data, haplotype

maps, SNP maps, expression profiling

data, and other genomic data become

available, these data will need to

be integrated with phenotypic,

pedigree, and experimental data

into a common, national database.

These databases will require a

standardized ontology of genotypes

and phenotypes and mechanisms to

encourage centralization of producer-

generated phenotypic data. The

National Center for Biotechnology

Information (NCBI) at the NIH is

currently the warehouse for genome

sequence information. However, NCBI

does not have adequate resources

to continue to maintain and curate

all genome sequence databases. In

addition, agricultural animal species

have unique population characteristics

(such as inbreeding or crossbreeding

that are not present in other species)

and require unique statistical tools for

appropriate analyses.

3) Centralized animal genetic resource

populations that are deeply

phenotyped and available to the

research community. A centralized

facility with sufficient technical

expertise to preserve unique

experimental animal populations,

collect genotypic and phenotypic

information on these animals, and

make the populations available to the

agricultural and biomedical research

communities (i.e., the Jackson labs

model) is needed. The emphasis in

these animal populations should be on

the development of rich phenotypic

measures for common traits of interest

as well as complex and difficult to

measure traits such as feed efficiency,

disease resistance, animal well-being,

product quality, and environmental

adaptability. Resource populations of

animals with divergent responses to

microbes, vaccines and therapeutics

are also needed. Repositories for cell

lines, DNA and RNA collections,

and gene expression resources for

all species should also be developed,

maintained and made readily

accessible to the scientific community.

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Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Discovery Science

The mission of the National Animal

Germplasm Program should be

broadened to become a coordinated

national repository for genomic DNA,

appropriate DNA libraries, tissues

and specialized cell lines for access by

publicly-funded, U.S. scientists.

4) Education and training of students,

scientists, and the public on

genome-enabled animal science

and opportunities that help prepare

the next generation of researchers

to work in interdisciplinary teams.

Particular emphasis should be placed

on integrating quantitative genetics,

genomics, immunology, nutrition,

physiology, biochemistry, cell biology,

developmental biology, ecology,

engineering, physics, mathematics, and

computer science with development

of scientists who have a keen

appreciation for and knowledge of

animal production. There is a dearth

of qualified candidates for scientific

and technical support positions in

the animal industry. The critical mass

of expertise in animal genomics at

colleges and universities across the

globe that train these scientists is

diminishing at a rapid pace. The U.S.

faces the very real possibility of losing

our ability to train new scientists in

the integrated fields of quantitative

genetics, statistics, and computational

biology for animals unless this

trend is reversed. Undergraduate

animal sciences and related curricula

should contain sufficient exposure to

“omics” concepts and technologies,

as well as the social science aspects of

consumer acceptance of the application

of genome-enabled technologies

to animal production systems. In

addition, faculty development, student

recruitment and services, curriculum

development, instructional materials,

and innovative teaching methodologies

in agricultural animal genomics are

needed. A national animal genomics

commodity-specific model for

extension and outreach (based on

“regional” extension specialists)

will enable and facilitate effective

translation of genomics research and

resulting technologies to the animal

production sector and the public.

c

oncluSion

Quantitative animal genetics and

animal improvement programs have

led to tremendous improvements in

the efficiency of agricultural animal

production during the last 50 years.

Investments in genomic technology

from gene discovery to sequenced

genomes, as well as state-of-the-art

technology developed by the biomedical

research community, have animal

agriculture poised at the threshold of

the genomic revolution. Application of

new genomic technologies to animal

producers will improve the efficiency,

sustainability, biosecurity, and social

acceptance of animal production. This

Blueprint describes future research,

education, and extension efforts needed

to develop and deliver animal genome-

enabled technologies to the animal

industry. The Blueprint contains specific

1

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Discovery Science

recommendations for Infrastructure,

Discovery Science, and Science to Practice.

A summary of these recommendations is

provided in Appendix II.

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Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Infrastructure

Discovery Science

Ronnie D. Green (Chair)

National Program Leader

Animal Production

USDA-ARS

Muquarrab A. Qureshi (Co-Chair)

National Program Leader

Animal Genetics

USDA-CSREES

Peter C. Burfening

National Program Leader

Animal Genome Programs

USDA-CSREES

Hans H. Cheng

Research Geneticist

USDA-ARS

Avian Disease and Oncology Lab

East Lansing, Michigan

Noelle E. Cockett

Dean

College of Agriculture

Utah State University

Logan, Utah

Deb Hamernik

National Program Leader

Animal Physiology

USDA-CSREES

Steven Kappes (Ex-Officio)

Deputy Administrator

Animal Production & Protection

USDA-ARS

Mark A. Mirando

National Program Leader

Animal Reproduction, Growth, and

Nutrient Utilization Programs

USDA-CSREES

Anna C. Palmisano (Ex-Officio)

Deputy Administrator

Competitive Programs Unit

USDA-CSREES

Daniel L. Pomp

Professor

Departments of Nutrition and

Cell and Molecular Physiology

University of North Carolina

Chapel Hill, North Carolina

Gary A. Rohrer

Research Geneticist

USDA-ARS

U.S. Meat Animal Research Center

Clay Center, Nebraska

Curt Van Tassell

Research Geneticist

USDA-ARS

Bovine Functional Genomics and

Animal Improvement Programs Labs

Beltsville, Maryland

James Womack

Distinguished Professor

Department of Pathobiology

College of Veterinary Medicine and

Biomedical Sciences

Texas A&M University

College Station, Texas

A word about the USDA Animal Genomics Strategic Planning Task Force:

Following the recommendation of the Interagency Working Group on Animal Genomics, a task force was

established in January 2006 by USDA’s Under Secretary for Research, Education and Economics, Joseph Jen.

This task force was charged with developing a Blueprint for USDA efforts in agricultural animal genomics.

Members include:

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REFERENCES

American Competitiveness Initiative

Leading the World in Innovation.

Domestic Policy Council. Office of

Science and Technology Policy. February

2006. http://www.whitehouse.gov/

stateoftheunion/2006/aci/

Buzby, J.C., Wells, H.F., and Vocke, G.

2006. Possible Implications for U.S.

Agriculture from Adoption of Select

Dietary Guidelines. http://www.ers.usda.

gov/Publications/ERR31/

Burfening, P., Claxton, J., Green, R., and

Warkup, C. 2006. The Future of Livestock

Genomics. Report on a Workshop Held

in Brussels 17-18 July 2006 Under the

Auspices of the US-EC Task Force on

Biotechnology Research. www.ec.europa.

eu/research/biotechnology/ec-us/docs/

ec-us_workshop_animal_genomics_july_

2006_en.pdf

Collins, F.S., Green, E.D., Guttmacher,

A.E., and Guyer, M.S. 2003. A Vision for

the Future of Genomics Research. Nature

422:835-47.

Coordination of Programs on Domestic

Animal Genomics: A Federal Framework.

National Science and Technology Council.

Committee on Science. Interagency

Working Group on Domestic Animal

Genomics. September 2003. www.ostp.

gov/nstc/html/Animal_GenomeWEB.

pdf

Food and Agriculture Organization of the

United Nations. 2002. World Agriculture:

Towards 2015/2030 Summary Report.

http://www.fao.org/docrep/004/

y3557e/y3557e00.htm

Gibbs, R.A., Weinstock, G., Kappes, S.M.,

Schook, L.B., Skow, L., and Womack,

J. 2002. Bovine Genomic Sequencing

Initiative: De-Humanizing the Cattle

Genome. http://www.genome.

gov/Pages/Research/Sequencing/

SeqProposals/BovineSEQ.pdf

Green, R.D., Qureshi, M.A., Long, J.A.,

Burfening, P.J., and Hamernik, D.L. 2007.

Identifying the Future Needs for Long-

Term USDA Efforts in Agricultural Animal

Genomics. Int J Biol Sci 3:185-191.

Hamernik, D.L. and Adelson, D.L.

2003. USDA Stakeholder Workshop on

Animal Bioinformatics: Summary and

Recommendations. Comp Funct Genom

4:271-274.

Hamernik, D.L., Lewin, H.A., and Schook,

L.B. 2003 Allerton III. Beyond Livestock

Genomics. Animal Biotechnology 14:77-82.

International Chicken Genome

Consortium. 2004. Sequence and

Comparative Analysis of the Chicken

Genome Provide Unique Perspectives on

Vertebrate Evolution. Nature 432:695-716.

International HapMap Consortium. 2005.

A Haplotype Map of the Human Genome.

Nature 437:1299-1320.

18­

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

National Academy of Sciences. 2002.

Exploring Horizons for Domestic Animal

Genomics: Workshop Summary. (Ed. Pool R

and K Waddell). National Academy Press,

Washington, DC (42 pp).

Rosegrant, M.W., Paisner, M.S., Meijer,

S., Witcover, J. 2001. 2020 Global Food

Outlook: Trends, Alternatives, and

Choices. International Food Policy

Research Institute, Washington, D.C.

http://www.ifpri.org/pubs/fpr/fpr30.

pdf

Schook, L.B. (ed) 1997. Proceedings of

the Allerton III Conference on Genetic

Analysis of Economically Important Traits

in Livestock. Animal Biotechnology 8:1-150.

United States Department of Agriculture

Strategic Plan for 2005-2010. June 2006.

http://www.ocfo.usda.gov/usdasp/

usdasp.htm

Wong, G.K. et al. International Chicken

Polymorphism Consortium. 2004. A

Genetic Variation Map for Chicken

with 2.8 Million Single-Nucleotide

Polymorphisms. Nature 432:717-22.

1

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

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Appendix I

Alignment of Blueprint Priorities

With National Issues and USD

A Strategic Goals

Competitiveness

Animal

of American

Pr

oduction

Health &

Pr

oduct

Food

pr

oducts*

Efficienc

y**

W

ell-Being***

Biosecurity***

Quality****

Saf

ety***

T

raceability***

Sustainability**

Science to Practice Whole Genome Selection

X

X

X

X

X

X

Prediction of Genetic Mer

it

X

X

X

X

X

Precision Mating

X

X

X

X

X

X

Precision Management

X

X

X

X

X

Genome-Based

T

r

aceability

X

X

X

X

X

X

Disco

ver

y Science

Gene Disco

v

er

y

X

X

X

X

X

X

X

X

Systems Biology & Gene Mechanisms

X

X

X

X

X

X

X

Genetic Basis of Phenotypic

V

ar

iation

X

X

X

X

X

X

X

Animal Health &

W

ell-Being

X

X

X

X

X

X

X

Infrastructure Genomic

T

ools

X

X

X

X

X

X

X

X

Databases

X

X

X

X

X

X

X

X

Genetic Resources

X

X

X

X

X

X

X

X

Education and Outreach

X

X

X

X

X

X

X

X

*

Relates

to

USDA

Goal

1

(Enhance

International

Competitiveness

of

American

Agriculture)

**

Relates

to

USDA

Goal

2

(Enhance

the

Competitiveness

and

Sustainability

of

Rural

and

Farm

Economies)

***

Relates

to

USDA

Goal

4

(Enhance

Protection

and

Safety

of

the

Nation’

s

Agriculture

and

Food

Supply)

****

Relates

to

USDA

Goal

2

(Enhance

the

Competitiveness

and

Sustainability

of

Rural

and

Farm

Economies)

and

Goal

5

(Improve

the

Nation’

s

Nutrition

and

Health)

20

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

Discovery Science

Appendix II

Summary of the Animal Genomics Blueprint Priorities

Science to Practice:

1. Whole genome enabled animal selection.

2. Prediction of genetic merit of individual animals from genome-based data

combined with phenotypes.

3. Integration of genomic data into large scale genetic evaluation programs and the

use of genomic information to design precision mating systems.

4. Precision management systems to optimize animal production, health, and

well-being.

5. Genomic capabilities that enable parentage and identity verification (traceability).

Discovery Science:

1. Identify genes and gene products that regulate important traits in agricultural

animals such as disease resistance, animal well-being, feed efficiency, and product

quality.

2. Understand mechanisms that regulate agriculturally relevant genes in a systems

biology framework.

3. Define the mechanisms through which specific genes and genetic variation

influence phenotypes and phenotypic variation.

4. Understand the roles and interactions of host animal and microbial genomes and

environmental influences (e.g., animal feed, vaccines) for improving animal health,

well-being, and production efficiency.

Infrastructure:

1. Genomic tools to connect genotype to phenotype and elucidate pathways of

complex traits for all agricultural animal species. These genomic tools include

comprehensive, high resolution genome maps and assembled and annotated

genomic sequences.

2. National, comprehensive databases and the statistical and bioinformatics tools that

integrate genomic, phenotypic, and experimental information for each species.

3. Genetic resources such as centralized animal populations that are deeply

phenotyped as well as repositories for cell lines, DNA and RNA collections, and

gene expression resources for all species. The mission of the National Animal

Germplasm Program should be broadened to become a coordinated national

repository for genomic DNA, appropriate DNA libraries, and specialized cell lines.

4. Education and training of students, scientists, and the public on genome-enabled

animal sciences and opportunities that help prepare the next generation of

scientists. Particular emphasis should be placed on integrating quantitative

genetics, genomics, immunology, nutrition, physiology, biochemistry, cell biology,

developmental biology, ecology, engineering, physics, mathematics, and computer

science with development of scientists who have a keen appreciation for and

knowledge of animal production systems. Additional emphasis on extension and

outreach will enable and facilitate effective translation of genomics research and

resulting technologies to the agricultural animal production sector and the public.