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

Education & Training

Animal Resource Populations

Databases & Bioinformatics

Genomic Tools

Gene Discovery

Functional Genomics

Host:Pathogen Interactions

Systems Biology

Genome-Enabled Animal Selection

Precision Management Systems

Precision Mating Systems

Animal Identity/Traceability

Discovery Science

Science to Practice

Infrastructure

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

2

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

Science to Practice

Infrastructure

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.

11

Blueprint for USDA Efforts in Agricultural Animal Genomics 2008­–2017

Science to Practice

Infrastructure

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