The National Science and Technology Council (NSTC), a cabinet-level

council, is the principal means for the President to coordinate science

and technology policies across the Federal Government. NSTC acts as

a “virtual” agency for science and technology to coordinate the diverse

parts of the Federal research and development enterprise.

An important objective of the NSTC is the establishment of clear national

goals for Federal science and technology investments in areas ranging

from information technologies and health research, to improving

transportation systems, strengthening fundamental research, securing

the homeland, and strengthening the economy. This council prepares

research and development strategies that are coordinated across

Federal agencies to form an investment package that is aimed at

accomplishing multiple national goals.

Additional information regarding the NSTC can be obtained from the

NSTC website, http://www.ostp.gov/NSTC/html/NSTC_Home.html.

About the National Science and Technology Council
Coordination of Programs on

Domestic Animal Genomics:

The Federal Framework

Progress Report

June 2004

National Science and Technology Council

Committee on Science

Interagency Working Group on Domestic Animal Genomics

Interagency Working Group on Domestic Animal Genomics

Committee on Science

National Science and Technology Council

Chair

Joseph J. Jen

Under Secretary

Research, Education and Economics

U.S. Department of Agriculture

Members

Robert B. Bertram Lester Crawford

Chief Deputy Commissioner

International Research and Biotechnology Division Food and Drug Administration

Office of Environment and Science Policy

U.S. Agency for International Development Cliff Gabriel

Deputy Associate Director for Science

Adrienne Erbach Office of Science and Technology Policy

Chief Executive Office of the President

Agriculture Branch

Natural Resource Programs Jane Peterson

Office of Management and Budget Associate Director

Executive Office of the President Extramural Research

Program Director

Aristides Patrinos Comparative Genomics Program

Associate Director National Institutes of Health

Office of Biological and Environmental Research

U.S. Department of Energy Ronnie D. Green (Executive Secretary)

National Program Leader

William Zamer Food Animal Production

Program Director Agricultural Research Service

Ecological and Evolutionary Physiology U.S. Department of Agriculture

Division of Integrative Biology and Neuroscience

National Science Foundation

Associates

Rodney J. Brown Daniel W. Drell

Deputy Under Secretary Biologist

Research, Education and Economics Human/Microbial Genome Program

U.S. Department of Agriculture Office of Biological and Environmental Research

U.S. Department of Energy

Leland Ellis Marvin E. Frazier

Senior Liaison for Agriculture Director

Science and Technology Life Sciences Division

U.S. Department of Homeland Security Office of Biological and Environmental Research

U.S. Department of Energy

Muquarrab A. Qureshi

National Program Leader

Animal Genetics

Cooperative State Research, Education and Extension Service

U. S. Department of Agriculture
Table of Contents

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

II. Introduction ......................................................................................................................................... 3

III. Background ......................................................................................................................................... 4

IV. Progress Reported in the Past Year ................................................................................................... 6

Focus on Elucidating Genome Structure and Organization ..................................................... 6

Genetic and Physical Genome Maps.......................................................................................... 7

International Consortia Develop Bovine and Porcine BAC Maps ........................................ 7

Bovine BAC Map.......................................................................................................................... 8

Swine BAC Map ........................................................................................................................... 9

Integrated Maps Nearing Completion for Cattle, Pig, and Chicken ................................. 10

Domestic Animal EST Sequences in the Public Database Growing ................................... 11

Genome Sequencing ................................................................................................................... 14

Initial Draft of the Domestic Honeybee Genome Assembled ............................................. 14

Chicken Genome Drafted at Washington University............................................................ 15

Broad Institute, MIT Well Underway in Sequencing the Dog Genome ............................... 16

Unprecedented Partnership Launches the Bovine Genome Sequencing Project .......... 18

International Swine Genome Sequencing Consortium Formed ......................................... 20

Genomics-Derived Tools Critical in US BSE (Mad Cow Disease) Crisis .................................... 21

V. Plans for the Next Year ..................................................................................................................... 22

VI. Appendix ........................................................................................................................................... 27

Acknowledgements................................................................................................................................ 28

Photo Credits ........................................................................................................................................... 28

I. Executive Summary

The Interagency Working Group (IWG) on Domestic Animal Genomics was

chartered in 2002 with the charge of enhancing interagency communication

and awareness of the importance of agricultural and companion animal

species, increasing leverage of investments across government agencies, and

positioning of agriculture as a critical element of the Federal genomics

programs. The Committee on Science provides oversight over the IWG

activities. The membership of the IWG consists of 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), and U.S. Agency for International

Development (USAID). The IWG subsequently identified the following broad

strategic goals:

• Bring into place the programmatic elements needed to advance the study

and understanding of domesticated 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 (comparative genomics).

• 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.

• 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.

• Ensure that genomics data are freely available in the public domain and

genomics reagents and resources are available to the public.

• Increase the training opportunities for genomics and bioinformatics at all

levels of education.

• Coordinate and encourage international cooperation to achieve these

goals.

Coordination of Programs on Domestic Animal

Genomics: The Federal Framework

Progress Report

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 1
In September 2003, the IWG released its initial plan entitled “Coordination of

Programs on Domestic Animal Genomics: A Federal Framework” in which largescale sequencing, data management and bioinformatics, and functional

genomics were identified as the specific goals to be achieved in fiscal years

2003 to 2007 (see http://www.ostp.gov/NSTC/html Animal_Genome%7EWEB.pdf).

In this report, progress in the first year of the effort is presented. Highlights

include:

• Completion of bovine and chicken BAC maps with the same nearing

completion for swine.

• Progress on producing integrated physical and genetic maps for bovine,

swine, and chicken.

• Completion of the first draft assembly of the honeybee and chicken genome

sequences.

• Significant progress in completing the first assembly of the dog genome

sequence.

• Successful launching of the bovine genome sequencing project.

• Activities of the International Swine Genome Sequencing Consortium in

securing support to launch the porcine genome sequencing project.

• Successful application of genomics technology in addressing the US BSE

cattle situation.

Also reported are plans for the coming year for the IWG, including:

• Development of a plan for bioinformatics and functional genomics tool

development in agricultural animal research.

• Development of a broad-based functional genomics program in infectious

animal disease.

• Expanding the structural genomics infrastructure to include additional

species of interest.

• Consideration of genomics technology for animal traceability systems.

In the next year, all agencies participating in the IWG plan to continue support

of domestic animal genomics research based on the five-year plan. The IWG

and participating agencies recognize the rapid pace of developments in

animal genomics and that there will likely be new opportunities requiring IWG

attention as they become evident. The members of the IWG look forward to

continuing to work to effectively coordinate and facilitate federal efforts in this

important area.

2 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
II. Introduction

Domesticated animals have played a key role in human society through their

use as livestock, medical research models, and human companions. The

completion of the human genome DNA sequence in April 2003 marked an

important milestone in scientific knowledge. The research arising from it, called

genomics, provides a new opportunity to improve and understand

domesticated animals. Once a genome sequence is in hand, scientists use it to

identify new genes, discover and understand regulatory elements, and study

individual genes, their functional products on a molecular level, and their

interactions with other genes. Additionally, the sequence can be used to study

the evolution of genomes that will aid in understanding how molecular

mechanisms arose.

In the United States, livestock and companion animals are the backbone of

billion-dollar industries. Genomic studies of domesticated animals will yield an

understanding of the genetics and expression of genes important to improving

these species for greater food yields and improved animal health and human

nutrition. Even more importantly, comparative genomics will make significant

contributions to biomedical research and ultimately improved human health.

Understanding human biology based on insights from a diversity of species will

lead to advances in biomedical research and it is anticipated that it will

accelerate the development of new human and animal pharmaceuticals.

The inclusion of domesticated animals in a Federal genomics program serves

two primary purposes: 1) to increase the diversity of genomic sequence

available for studies that by comparison with the human genome DNA

sequence contribute to finding new genes and studying evolution at the

genome level; and 2) to generate genetic data critical to efficient and

sustainable animal agricultural production.

Genome sequencing projects are completed or underway for several animals

(including the laboratory mouse, rat, rhesus macaque) that serve as models for

studying human disease. Projects for sequencing the genomes of several

domesticated animals (chicken, cattle, honeybee and dog) have now entered

the genomic sequencing pipeline.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 3
III. Background

The charge to the Interagency Working Group on Domestic Animal Genomics

(IWG), which was established in 2002, was to enhance interagency

communication and awareness of the importance of agricultural and

companion animal species, to increase leverage of investments across

government agencies, and to position agriculture as a critical element of the

Federal genomics programs. The National Science and Technology Council’s

Committee on Science provides oversight over the IWG activities. The

membership of the IWG consists of 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), and U.S. Agency for International Development (USAID).

Upon convening, the initial deliberations regarding the task set forth to the IWG

led to an overarching statement of purpose:

The mission of the Interagency Working Group for Domestic

Animal Genomics is to enhance communication and

awareness of livestock and companion animal species of

importance to the food and agriculture system; leverage

Federal investments in large-scale genome sequencing and

genome analysis across government agencies; position the

food and agriculture system as a critical element of the

national genomics program; enhance dialogue and

cooperation among Federal agencies, universities, and

industry in the nation; and promote international cooperation

on domestic animal genomics research.

The IWG subsequently identified the following broad strategic goals:

• Bring into place the programmatic elements needed to advance the study

and understanding of domesticated 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).

• 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.

4 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
• 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.

• Ensure that genomics data are freely available in the public domain and

genomics reagents and resources are available to the public.

• Increase the training opportunities for genomics and bioinformatics at all

levels of education.

• Coordinate and encourage international cooperation to achieve these

goals.

The IWG determined that large-scale sequencing, data management and

bioinformatics, and functional genomics are the specific goals to be achieved

in fiscal years 2003 to 2007, including:

• Large-scale sequencing to produce draft genome sequences (8-fold

sequence coverage) of honeybee, chicken, dog, cattle, swine, and cat.

• Data management and bioinformatics to specifically support agriculturally

important species. This will support significant improvements in data

management and analysis software, allow greater data accessibility and

secure long-term maintenance, increase capabilities to deal with rapidly

accumulating data complexity as databases include functional information,

and provide more powerful tools to mine large genomes (individually and

comparatively).

• Functional genomics to specifically investigate agriculturally important

species. An increase in data for livestock genomes requires concomitant

investment in functional genomics to support genome annotation, the study

of gene regulation and expression, and species evolutionary relationships.

Researchers will have access to individual genes, which can be cloned and

characterized, the ability to scan entire genomes for specific functions, and

be able to gain new insights from comparisons to other genomes.

Quantitative trait loci will be accessible on a gene level, leading to studies

that will elucidate characteristics such as food productivity and disease

resistance and will lead to the ability to manipulate those traits more quickly

and effectively.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 5
IV. Progress Reported in the Past Year

Focus on Elucidating Genome Structure and Organization

The progress reported herein builds upon an impressive foundation of

agricultural and biological science. Research efforts, primarily over the past

century, have provided a vast amount of phenotypic and genotypic

information for a wide array of characters in livestock and companion animals.

Long-term large population studies have been employed, particularly in the

area of livestock production science, to develop technology to allow genetic

evaluation and subsequent selection to be practiced on breeding populations

in highly sophisticated planned breeding programs, especially for dairy and

beef cattle, layer and broiler chickens, and swine. As DNA-based technologies

were developed in the 1970s and 1980s, these well-characterized populations

were invaluable in providing opportunities to develop genetic linkage maps to

begin the search for genes affecting important traits. Highly saturated genetic

maps were developed for all of the major domesticated animal species during

the 1990s, allowing Quantitative Trait Loci (QTL) to be identified across many

species and for many measures of performance. In parallel, genetic studies of

the human were progressing with the development of genetic maps that were

used to identify genes important in human disease. It was recognized in the

late 1980s that progress in developing tools for agricultural or biomedical

application could be greatly accelerated by producing high-resolution physical

maps and ultimately the genome sequence of human and agricultural species.

The genome sequence is needed in order to find all of the genes in an

organism and begin to unravel how genes function and interact (i.e. functional

genomics). Knowledge of gene interactions leads to further research in

understanding proteins and their interactions and networks/pathways within the

cell.

The challenge presented by the ambitious goals set for the human genome

project stimulated rapid improvements in DNA sequencing strategies and

technologies in the past decade. Following the successful completion of the

human genome sequence and substantial progress in producing the sequence

of the major model species used in biomedical research, there continued to be

a need for sequencing of additional mammalian genomes, including

domesticated animals, to be used as a tool to find all of the genes and

regulatory elements encoded in the human genome. The approach used,

called comparative genomics, compares and searches for similarities in DNA

sequences from distantly related organisms. Less than half of these regions of

sequence similarity contain genes known to be highly conserved throughout

6 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
the evolutionary tree, and it is postulated that the remaining regions may

encode important regulatory elements. In the past two years, the National

Human Genome Research Institute (NHGRI) of the National Institutes of Health

included in its sequencing program the sequencing of genomes from species

whose sequence was expected to help find all of the genes and identify

regulatory elements in the human, mouse, and rat genomes through

comparative sequencing and evolutionary biology approaches.

During 2002, proposals were submitted to NHGRI to develop draft-quality

genome sequences for the chicken, cow, honeybee, pig, dog, and cat. All

were designated to be “high priority” for sequencing by NHGRI supported

sequencing centers (with the understanding that close evolutionary

relationships between dog/cat and cow/pig would only allow justification for

one of each pair of species to be sequenced in the NHGRI program) based

upon the value of their sequence data to better understanding of the human

genome thereby improving human health. Designation of high priority does not

automatically mean that a project will be undertaken by the NHGRI

sequencing program and in several cases, contributions from partners having a

significant interest in obtaining the genomic sequence of particular organisms

have been required. A primary emphasis of the IWG since its inception has

been how to bring together the resources and partnerships to allow these largescale sequencing projects to come to fruition for domestic animal species.

The following summaries highlight the major accomplishments during 2003

along the pathway to completion of the genomics infrastructure needed to

advance the genomic studies of the chicken, cow, dog, honeybee, pig, and

cat. The progress to date has occurred as a two-step process. The first step is

the completion of infrastructure organizing the genetic (linkage) and physical

{bacterial artificial chromosome (BAC) and radiation hybrid (RH)} maps for

each of the important species. The resulting integrated genome maps then

become the foundational “scaffolding” upon which whole genome

sequencing is performed—resulting in the ultimate full sequence map of the

genome.

Genetic and Physical Genome Maps

International Consortia Develop Bovine and Porcine BAC Maps

The availability of physical maps, and eventually the DNA sequence of the

bovine and porcine genomes, will transform genetic research in these species.

Such maps will greatly facilitate the identification of genes affecting production

traits, disease susceptibility, animal health and product quality and nutritional

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 7
value. The elucidation of these genomes will also benefit human medicine by

identifying novel genes and their function that are critical for human health. It is

important that the genetic and physical maps, and the reagents used to build

them, are freely accessible and in the public domain. The bovine and swine

genomics research communities need additional laboratory resources to allow

more efficient use of current human and mouse mapping information to solve

production inefficiency and health problems and contribute to increasing the

global competitiveness of these livestock industries.

Bovine BAC Map

An international effort (International Bovine BAC Mapping Consortium; IBBMC)

was initiated to develop a physical BAC-based map of the bovine genome.

Clones from three publicly available bovine BAC libraries were fingerprinted

and end-sequenced to develop the bovine BAC map. The three BAC libraries

were generated from three common breeds, Holstein, Hereford, and Angus. A

total of 295,000 clones have been fingerprinted (15.8 X coverage) from these

three libraries. Additional fingerprinting (100,000 clones) was performed on a

fourth BAC library by INRA (L’Institut National de la Recherche Agronomique),

France and is being end-sequenced (12,000 clones to date). Overall, a total of

160,000 clones have been sequenced with 140,000 clones having both ends

sequenced. End sequencing information from an additional 100,000 clones by

the INRA and international effort will be added and integrated in the near

future. All sequence data are publicly available (www.ncbi.nih.gov/Genbank).

The construction of the integrated BAC map is in progress. The initial contig

assembly generated 14,000 contigs with 2 or more clones per contig and 30,000

singletons. By utilizing the information in the human map and sequence, the

contigs were merged reducing the number to 2,622 with 621 of these contigs

containing 199,326 clones that are anchored to human chromosomes. A 2,000

marker radiation hybrid (RH) map has been generated that will be used to

further merge contigs and anchor contigs to the human and bovine map.

Publication of the bovine BAC map is planned for late 2004.

The BAC map was used as one of the justifications to sequence the bovine

genome since this would be the first genome to be sequenced with a BAC map

nearly completed prior to the start of sequencing. The sequencing of the

bovine genome has now been funded and an element of the sequencing

strategy will be to perform “light” sequencing of BAC clones across the

genome. 19,000 clones have been selected from the Hereford library based

upon the BAC map for this purpose. Additionally, selected BACs from regions of

high research interest will be chosen for high-quality sequencing.

8 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
The participants of the IBBMC include USDA/ARS (Beltsville, Maryland and Clay

Center, Nebraska), Texas A&M University, University of Illinois, The Institute for

Genomic Research, Children’s Hospital Oakland Research Institute, The

University of Alberta and Alberta cattlemen (Alberta Livestock Genomics

Initiative), INRA (France), AgResearch (New Zealand), CSIRO (Australia),

EMBRAPA (Brazil), Roslin Institute (Scotland), British Columbia Cancer Agency

Genome Sciences Centre (Canada), and the Alliance for Animal Genomics

Research.

Swine BAC Map

The swine genomics research community organized a similar and parallel effort

to that employed by the international bovine consortium to produce a porcine

BAC map. The participants in the International Porcine BAC Mapping

Consortium (IPBMC) include the University of Illinois, USDA/ARS U.S. Meat Animal

Research Center, Roslin Intitute, Sanger Institute (U.K.), INRA, and the Korean

Livestock Institute.

Clones from five available BAC libraries are being fingerprinted and endsequenced in the swine effort (generated from Duroc, Korean, Meishan and

Large White breeds). Thus far, a total of 300,300 clones have been fingerprinted

with 225,000 clones having both ends sequenced. Additional clones are

scheduled for end-sequencing in the spring of 2004. Similar to the model used

by the bovine BAC-map consortium, the porcine map will be anchored to

human chromosomes using a RH map currently being produced by integration

of the 12,000-rad INRA and 7,000-rad INRA-University of Minnesota RH panels.

All sequence data from this effort are being deposited in GenBank

(www.ncbi.nih.gov/Genbank).

Construction of the integrated maps is to be conducted at the Sanger Institute

during the second quarter of 2004. The IPBMC will meet at the Sanger Institute

in June 2004 to review the initial map and to finalize plans for publication of the

integrated BAC map. The first public presentation of the integrated map is

slated for the International Society of Animal Genetics meetings in Tokyo in

September 2004.

The plans of the IPBMC also include contribution of a minimum tiling path of

clones from the Duroc library to be eventually used in developing the porcine

whole genome sequence assembly (see subsequent article on page 20 of this

report).

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 9
Integrated Maps Nearing Completion for Cattle, Pig, and Chicken

Integration of genetic linkage maps with physical maps and sequences is an

essential component of efforts to link traits of agricultural interest (productivity,

disease resistance, etc.) to the genes encoding alleles that determine the

phenotype. This linkage requires genes or markers that are both polymorphic

(capable of linkage mapping in populations) and easily assignable to physical

maps. While there is growing interest in single nucleotide polymorphisms (SNPs),

simple tandem repeats (STRs, also called “microsatellites”) have been most

heavily employed in domestic animals, due to their widely polymorphic nature.

Statistical approaches to build integrated maps for livestock species can

consolidate information from independent maps and capitalize on

complementary resolution of physical and genetic data sets to resolve marker

order. Genetic data used for linkage mapping can position markers separated

by recombination along a chromosome, but lacks the resolution necessary to

reliably order close markers. Physical mapping data sets, such as radiation

hybrid (RH) panels, can reliably order close markers, but lack long-range

resolution to order groups of widely separated markers. Simultaneously solved

maps representing both linkage and RH data take advantage of each to order

markers more reliably.

The first likelihood-based whole-genome bovine map integrating linkage and

RH data was completed by USDA/ARS’s Roman L. Hruska U.S. Meat Animal

Research Center (MARC) at Clay Center, Nebraska, and is now available to the

International Bovine BAC Map Consortium. The map combines data from two

radiation hybrid panels, the 3000-rad European Union (COMRAD) panel and the

5000-rad Texas A&M/University of Illinois panel, with linkage data from the MARC

reference families. Over 6,300 distinct markers are represented, with 1,381 of

these represented in the linkage and at least one RH data set. Alignment

between 2,061 marker sequences and human genomic sequence provides the

basis for a bovine-human comparative map. Overlap between marker and

BAC end sequence alignments on the human genome connects 1,504 markers

to the bovine BAC map, augmenting 574 markers physically assigned to BAC

clones. Besides providing a bovine order to anchor BAC contig assembly and

ultimately guide bovine sequence assembly, the integrated map has had a

significant positive impact on the efficiency of the SNP discovery process to

develop new markers targeted to chromosomal regions known to harbor loci

influencing economically important traits. Further development of the

integrated bovine map will incorporate BAC data, providing another level of

resolution to refine marker order.

10 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
The swine whole-genome integrated map has been constructed in

collaboration with France’s INRA. More than 1,000 genetic markers from MARC

were included in the analyses with over 3,000 markers ran across the INRAUniversity of Minnesota pig RH 7,000-rad panel. Approximately 750 markers were

included in both data sets. The genetic map developed at MARC has been

dramatically expanded recently and now contains over 3,000 typed loci. One

thousand of the new markers are single nucleotide polymorphisms developed

from EST sequence data generated in the pig. These markers are crucial to

developing a high-resolution comparative map and permit integration of the

genetic, RH and BAC maps in the near future.

Genetic linkage maps for the chicken expanded rapidly in the 1990s with the

application of DNA-based marker systems. The consensus linkage map (Schmid

et al., Cytogenet. Cell Genet. 90, 2000) covers about 4000 cM, including over

2000 markers. Early efforts to generate a physical map of the chicken genome

led to the development of several BAC libraries (Crooijmans et al., Mammal

Genome, 11, 2000; Lee et al., Anim. Gent. 34, 2003). These now have been used

to generate genome-wide BAC contig maps that place chicken genes and

markers in specific molecular locations (Ren et al., Genome Res., 13, 2003;

Warren et al., manuscript in preparation). A first generation BAC map, partially

integrated to the linkage map, is now available (Ren et al., Genome Research

13:2754) and a much-improved version will be published soon by the

Washington University Genome Sequencing Center. This map will be integrated

both to the linkage map and to the full genome draft sequence using the same

approaches as previously described for cattle and swine.

Given the draft level of the genome sequences now assembled for the

chicken, in progress for the cow and proposed for the pig, map integration

efforts will be important tools in assessing the quality of the sequence

assemblies. The genome sequences will also provide marker sets (both SNP and

STR) that will permit much higher resolution in future QTL mapping efforts for the

purposes of mechanistic analyses and marker-assisted selection.

Domestic Animal EST Sequences in the Public Database Growing

The number of ESTs (Expressed Sequence Tags) in the dbEST database from

domestic animals (http://www.ncbi.nlm.nih.gov/dbEST/) continues to increase

at a rapid rate. As of February 2004, 1,530,000 ESTs had been deposited with

the largest number coming from the chicken, cattle, and swine research

communities.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 11
Researchers are using the EST sequence information in dbEST in an increasing

number of ways, particularly as mapping tools and for the development of

gene expression profiling tools. The chicken is an excellent example of progress

in this area. It is estimated that a total of over 600,000 chicken EST sequences

have been determined (Burt and Pourquié, Science, 300, 2003) with more on

the way. Chicken homologues to most mammalian genes can now be found in

silico by searching the chicken EST and/or the non-redundant sequence

databases (e.g., http://www.ncbi.nlm.nih.gov/blast). Brown et al. (Nature Rev.

Genet. 4, 2003) reported that the chicken EST set already available showed

strong matches to over 90% of the human disease genes in the “morbid map”

of the Online Mendelian Inheritance in Man database (http://www.ncbi.nlm.

nih.gov/Omim). Chicken EST contigs provide the basis for the construction of

microarrays, used in global profiling of gene expression. Chicken gene

microarrays have been used to analyze changes in mRNA levels in response to

infection with Marek’s Disease Virus (Liu et al., Animal Genet. 32, 2001) and

Eimeria (Min et al., Appl. Microbiol. Biotechnol. 62, 2003) and in neoplasias

induced by c-myc and c-myb over-expression (Neiman et al., Proc. Natl. Acad.

Sci. U.S.A., 98, 2001, 2003). A 13,000 transcript chicken microarray (glass slide) is

available from the Fred Hutchinson Cancer Research Center Genomics Facility,

and more complete arrays using a variety of platforms are being planned.

12 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
Number of EST Entries in GenBank from Domestic Animals

(data from dbEST/GenBank/NCBI as of April 2004)

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 13

0

50000

100000

150000

200000

250000

300000

350000

400000

450000

500000

Chicken

Cattle

Swine

Rainbow trout

Honey bee

Dog

Channel catfish

Horse

Carp

Rabbit

Sheep

Turkey

Goat
Genome Sequencing

Initial Draft of the Domestic Honeybee Genome Assembled

The honeybee (Apis meliferia) genome is the latest insect species, after the

mosquito and flies, to be fully sequenced and made available to the public.

Sequences from the honeybee will inform the medical sciences by improving

research based on the Drosophila insect model, as well as providing information

about behavior, development, and human immune reaction. The draft

honeybee genome sequence is expected to provide insights into the impressive

learning ability of these insects and may provide insights into learning and

neurological diseases of humans. Additionally, human immune response to

honeybee venom is an important medical problem in the United States. The

honeybee sequence may also provide insights into important medical questions

related to aging and reproduction. The honeybee genome sequence will also

be used to address critical problems related to the agricultural importance of

this species, ranging from disease resistance to nutrition, reproduction, and

behavior. Finally, as a more distant relative of the three fly species whose

genomes are available, honeybees provide a new reference point for

comparative genomics across the insects, a group of worldwide importance for

both human and ecosystem health. The request to NHGRI for sequencing of

the honeybee can be found at http://www.genome.gov/10002154.

The honeybee genome sequence was produced from January to August of

2003, at the Baylor College of Medicine’s Human Genome Sequencing Center

and includes both short-insert or shotgun clones (2 million sequence reads) and

end sequences from BAC clones (1.3 million sequence reads). The shotgun

sequence was compiled into an initial assembly (labeled Release 1.0) on

December 11, 2003. This assembly was improved and released as version 1.1 in

January 2004 and is now being analyzed by the insect genomics community.

Assembly 1.1 includes 11,600 scaffolds covering a genome of 206 Mbp, with an

N50 length of 223 kb. Forty percent of the assembly is covered by anchored

and oriented scaffolds (n = 197). 94% of the 1,050 known honeybee markers are

present in the assembly along with whole or partial sequences for 95% of genes

described previously. Automated gene predictions using this and future

assemblies will provide lists of known and de novo genes for honeybees. These

predictions will be followed by efforts at Baylor and other institutions to manually

annotate genes of interest to the medical and agricultural communities.

Assembly 1.1 used existing markers from known honeybee chromosomes to

establish a physical map for bees, a product that will prove useful both for

14 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
placing genes of interest and for agricultural goals such as marker-assisted

breeding. This map will evaluate the need to fill sequence gaps in critical

areas, and will help predict the feasibility of marker or locus-specific breeding

tools for honeybees. Future assemblies will be improved by the addition of BAC

end sequences and other sequences generated to improve the sequence

depth in targeted regions.

Funding for this project came from NHGRI ($6.9M) and USDA ($750K).

(Viewable on the web at: http://hgsc.bcm.tmc.edu/projects/honeybee/)

Chicken Genome Drafted at Washington University

The chicken is the first avian species for which whole genome sequence data is

available in the public domain. When first proposed to NHGRI in 2002 (see

original white paper proposal at: http://genome.wustl.edu/projects/chicken/

Chicken_Genome.pdf ), the chicken was identified as an extremely valuable

species for genome sequencing due to: 1) its premier status as a primary model

organism for studies in embryology and development, viruses and cancer,

immunology, and gene regulation; 2) novel aspects of its biology relevant to

human biology such as the Z/W sex determination system and high

microchromosome content; 3) its intermediate evolutionary position between

the mouse and fugu genomes; 4) its potential for providing a better

understanding of the evolution of gene order and arrangement; 5) the wealth

of genomics resources available from the chicken research community; and 6)

its clear and growing importance as a source of animal protein in world

agricultural production and the food system. Recent outbreaks of avian flu

have accelerated scientists’ interest in learning more about the chicken

genome and how genetic variation may play a role in the susceptibility of

different strains to the disease.

On March 1, 2004, NHGRI announced that a team led by Richard Wilson, Ph.D.,

from the Washington University School of Medicine in St. Louis successfully

assembled the genome of the Red Jungle Fowl, Gallus gallus, which is the

ancestor of domestic chickens. Sequencing of the chicken genome began in

March 2003. NHGRI provided about $13 million in funding for the project.

The Washington University researchers have deposited the initial assembly,

which is based on seven-fold sequence coverage of the chicken genome

(approximately 1 billion bases), into GenBank (www.ncbi.nih.gov/Genbank). In

turn, GenBank will distribute the sequence data to the European Molecular

Biology Laboratory’s Nucleotide Sequence Database, EMBL-Bank

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 15
(www.ebi.ac.uk/embl/index.html), and the DNA Data Bank of Japan, DDBJ

(www.ddbj.nig.ac.jp).

To facilitate comparative genomic analysis, the researchers also have aligned

the draft version of the chicken sequence with the human sequence. Those

alignments can be scanned using the University of California, Santa Cruz’s

Genome Browser, (http://genome.ucsc.edu/cgi-bin/hgGateway); the National

Center for Biotechnology Information’s Map Viewer, (www.ncbi.nlm.nih.gov/

mapview); and the European Bioinformatics Institute’s Ensembl system,

(www.ensembl.org).

In addition, using the Gallus gallus genome sequence assembled by

Washington University as a reference framework, an international team, led by

the Beijing Genomics Institute in China and supported by the Wellcome Trust in

Great Britain, has created a map of genetic variation for three different strains

of domestic chickens. The strains were a broiler strain from the United Kingdom,

a layer strain from Sweden and a Silkie strain from China. To make the map,

researchers identified and analyzed about 2 million genetic variation sites,

mostly SNPs. The genetic variation data will soon be deposited into GenBank,

from which the data will be freely accessible to researchers worldwide.

The project team has proposed to conduct a pre-finishing phase in 2004 to

close gaps, extend the size of sequence contigs and enhance overall quality of

the draft sequence. A crude analogy would be if the sequence is viewed as a

book, pre-finishing takes the product from an unbound collection of thousands

of loose-leaf pages to an ordered and bound manuscript. This process will

provide a much more valuable and reliable product for end users and is very

cost effective, as the clone libraries remain readily available for automated resorting. Funding for the pre-finishing project is under consideration by USDA.

For further information about the chicken genome project see (http://

genome.wustl.edu/projects/chicken).

Broad Institute, MIT Well Underway in Sequencing the Dog Genome

Dogs are unique among mammalian species in the extent of variation they

show in morphological traits such as height, weight, mass, shape, and behavior.

Yet, within each breed, key traits are inherited within extremely narrow limits. No

other mammalian species presents natural variation on such a scale, yet

individuals from nearly any breeds can be mated to yield fertile offspring.

16 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
Given the aggressive breeding programs needed to reproducibly generate

animals of distinctive size, shape and behavior, it is not surprising that purebred

dog fanciers have also produced closed breeding populations, which carry

over 400 inherited disorders. Genetic diseases are predicted to occur with high

frequency in populations with closed gene pools and in which breeding of

close relatives is used to propagate desired traits. Breeds established from a

small number of founders and expanded rapidly to meet breeders’ and

consumers’ demands suffer the most due to a combination of random drift and

inbreeding depression. Autosomal recessive and complex traits present the

biggest problem as the status of asymptotic carriers may not be suspected until

several litters have been produced. This includes diseases such as cancer, heart

disease, deafness, blindness, motor neuron disease, skin disorders, and a host of

autoimmune disorders, each of which has been difficult to study in humans.

The physiology, disease presentation and clinical response of dogs often mimic

human diseases closely. Thus, positional cloning of genetic diseases in the dog

can inform us about the genetic basis or susceptibility to similar diseases in

humans.

Because of the potential of the dog as a model for studying human disease,

the sequencing of the dog genome was approved by NHGRI in 2002 and is

now nearing completion at the Broad Institute, MIT. A female Boxer named

Tasha was chosen for sequencing because among the breeds examined by the

Broad investigators the Boxer has the lowest amount of variation in its genome

and therefore is likely to give an easily assembled genome sequence.

The sequencing of Tasha has now been completed to 6.5-fold coverage of the

genome and sequence assembly is underway. The sequence traces are

available at http://www.ncbi.nih/Traces/trace.cgi?. The assembly will be

posted in late spring of 2004 and will be aligned against the human sequence.

Automated annotation of the genome will also be provided. Tasha’s sequence

will then be compared to 100,000 sequence reads from 20 other breeds to

generate approximately 25,000 SNPs to be used in genetic studies of the dog.

For more information about the dog genome project see: http://

www.broad.mit.edu/media/2003/pr_03_tasha.html.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 17
Unprecedented Partnership Launches the Bovine Genome Sequencing

Project

On December 12, 2003, Secretary of Agriculture Ann Veneman and Francis

Collins, Director of the National Human Genome Research Institute of NIH, jointly

announced the launching of the International Bovine Genome Sequencing

Project (BGSP). This milestone was reached after a monumental effort to build

an international consortium to fund the $53M project.

In 2002, NHGRI identified the cow as a high priority through its proposal review

process (white paper proposal can be viewed at http://www.genome.gov/

10002154). At that time, NHGRI indicated that its support for the bovine genome

project was dependent upon raising matching funds. Over the course of the

following year, the IWG, with the assistance of the Alliance for Animal Genomics

Research, worked to bring together an international consortium to provide the

matching funds needed for the project. The International Bovine Genome

Sequencing Consortium (IBGSC) was formed of the funding agencies that are

contributing funds to match the total needed for the project. The group

consists of (with funding contribution): National Institutes of Health, NHGRI

($25M), USDA ($11M), State of Texas ($10M), Genome Canada ($5M), Australia’s

CSIRO ($1M), Ag. Research New Zealand ($1M), and US Cattlemens Beef Board,

Texas, and South Dakota Beef Councils ($820K). The project is underway at the

Baylor College of Medicine’s Human Genome Sequencing Center, Houston, TX

18 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
(BCM-HGSC), utilizing the international bovine BAC map as the scaffolding

upon which to do the sequencing (see previous section of this report).

The goals of the project are to produce a draft sequence coverage, assembly

and primary automated annotation of the bovine genome, including SNP

discovery, full-length cDNA sequencing and finishing of a selected set of BACs.

The genomic sequencing goal is 6-fold coverage (WGS and BAC skims

combined) with an additional 1-fold coverage from WGS SNP discovery

sequencing. This draft coverage will be augmented by finishing of 75 Mb of

sequence from regions that contain genes influencing important traits. The

cDNA sequencing will provide nearly 10,000 sequences.

The goal of Phase I will be to produce and assemble a draft bovine genome

sequence, including a SNP discovery component and production of full-length

cDNA sequences. The BCM-HGSC is the lead center in this phase and will

coordinate the overall conduct of the project. The Genome British Columbia

Sequencing and Mapping Platform (GBCSMP) at the British Columbia Cancer

Agency (BCCA) will participate in this phase of the project through production

of full-length bovine cDNAs. The annotation of the bovine genome sequence,

although not funded through the IBGSC, is being carried out by the European

Bioinformatics Institute (EBI) with funding from the Biotechnology and Biological

Sciences Research Council (UK) in collaboration with the BCM-HGSC. Phase I of

the project is targeted for completion in late 2005.

Project oversight is being performed by a Bovine Genome Sequencing Project

Advisory Committee (BGSPAC). This committee is comprised of representatives

from each contributing funding agency, a scientist chosen by that funding

agency and a representative from each sequencing center. Ex-officio

members include a representative of the Alliance for Animal Genomics

Research, and a representative of the authors of the “white paper” proposal.

Steven Kappes (MARC) and George Weinstock (BCM-HGSC) are co-chairs of

this committee.

As of March 1, 2004, a total of 2,500,000 sequence reads had been deposited in

the trace archive (amounting to ~0.5-fold sequence coverage). The sequence

is available at http://www.ncbi.nig.gov/Traces/trace.cgi?. Work on the BAC

tiling path had also commenced with the construction of shotgun libraries.

Efforts during the first three quarters of 2004 are being focused on completion of

the whole genome shotgun portion of the project. Additionally, planning of the

SNP discovery and full-length cDNA portions of the effort are underway by the

BGSPAC.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 19
Further information about the bovine genome project is available at: http://

hgsc.bcm.tmc.edu/projects/bovine/.

International Swine Genome Sequencing Consortium Formed

Recent completion of the human genome sequence provides the starting point

for understanding the genetic complexity of humans and how genetic variation

contributes to diverse traits and disease. Additional species must be

sequenced to resolve the genetic complexity of human evolution and to

effectively use genetic information in veterinary and human medicine. The pig

occupies an evolutionary position within mammals distinct from primates and

rodents but close to the bovine and dog. Its importance in biomedical

research and agriculture has led to the development of genomic resources

that will be extremely important to the research community studying the pig.

The pig has been widely used as a biomedical model for many years, and is

expected to play a critical role in research directed toward understanding

human obesity.

Consumption of pork continues to grow worldwide and pork represents 43% of

all red meat eaten in the world. Given its importance in modern animal

agriculture, obtaining the complete genome sequence of the pig is imperative.

Such scientific information will lead to improved performance and production,

decreased problems with porcine diseases and reduced environmental and

welfare concerns.

Leaders from the pig genetics community met in France in September 2003 and

established the International Swine Genome Sequencing Consortium (ISGSC)

with representation from the US, UK, France, Denmark, Korea, Japan, and

China. The goals of the ISGSC are to coordinate the scientific and funding

activities associated with sequencing the pig genome. The scientific strategy

includes: (1) contig sequencing (~2X coverage) and the assembly of all

sequences at a major genome sequencing center and (2) whole genome

shotgun sequencing (~5X coverage) that will be conducted at various centers

around the world. All data will be rapidly placed in the public domain. Larry

Schook from the University of Illinois is serving as chair of the consortium.

Similar to the approach being utilized in the bovine genome sequencing

project, the international swine BAC map will be used as the scaffolding for the

sequencing effort. The goal of the ISGSC is to secure the necessary funding

required (approximately $40M) for the project by October 2004.

Commitments thus far to the project include release of the ~.7-fold whole

genome shotgun sequence from the Sino-Danish pig project ($5M in kind), a

pledge from Korea to contribute WGS at NLRI ($2M in kind), and release of BAC20 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
end sequence from the Sanger Center ($3M in kind), Roslin Institute ($1M in

kind), Iowa State University ($0.3M), and the University of Illinois ($1M in kind).

Meetings have been held with USDA, the U.S. pork industry (Pork Board and

National Pork Producers Council), the European Commission, Genome

Canada, the Wellcome Trust, BBSRC, DEFRA, INRA and the Danish, Canadian,

and UK pork industries to explore potential direct funding of the project.

Genomics-Derived Tools Critical in US BSE (Mad Cow

Disease) Crisis

When the first index case of bovine spongiform encephalopathy (BSE), more

commonly referred to as “mad cow disease,” was reported in Washington state

in December of 2003, little did anyone know that it would become one of the

first major cases for the application of genomics technology to providing a

valuable and rapid solution in a crisis situation in animal agriculture. Following

the identification of the diagnosis of this animal, U.S. beef market prices

dropped precipitously, due to pressure imposed by the closure of most of the

major export markets to U.S. beef.

Shortly after the identification of the BSE case, records associated with the

particular cow in question indicated that she was originally imported from

Alberta, Canada, where a similar case of BSE had been identified several

months earlier. However, the records did not unequivocally prove her origin.

Fortunately, the records identified the sire and other relatives of the BSE index

case; furthermore, their tissues were available for genetic analyses. The

availability of these tissue samples permitted rapid pedigree verification, using

genomic technology, and thus confirmed the records indicating the Canadian

origin of the BSE index cow.

The technology used in this case was developed in 2002 by ARS scientists Mike

Heaton and coworkers at the USDA/ARS U.S. Meat Animal Research Center,

Clay Center, Nebraska. They identified 32 selected single nucleotide

polymorphisms (SNPs) in cattle that provided very accurate identification of

individual animals. This SNP battery was derived from hundreds of SNPs and

chosen for maximum allelic diversity. Based upon results from multiple breeds,

this genotyping system is capable of discriminating between any two random,

unrelated individuals in the population at a probability level of 2x10-13 (i.e. odds

ratio of 1:1 trillion).

Using this genotyping test, ARS scientists Will Laegreid, Mike Clawson, and Mike

Heaton were able to provide strong scientific evidence that the Washington

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 21
22 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK

state index cow was one of a group of 81 females that had crossed the U.S.

border from Canada several years earlier. This provided the missing link in the

traceability of this female to verify that she was born prior to the 1997

implementation of a full ban on animal protein feeding in Canada.

A month before the Washington state BSE case was identified, ARS scientists

reported the complete prion gene sequence variation in U.S. cattle. A quick

comparison of results showed that the BSE index cases did not have novel prion

gene sequences. This was important because DNA sequence analysis of both

the May 20th, 2003, Canadian BSE case and the Washington state case had

revealed apparently novel, but different, mutations in their prion gene

sequences. This would have otherwise suggested the occurrence of “sporadic

BSE,” i.e. not related to contaminated feed. Together, the new bovine genomic

tools had an immediate and positive impact on the beef industry, DNA

traceback, and animal disease control.

V. Plans for FY 2004

Beyond Sequencing–Focusing on Bioinformatics and Functional

Genomics Tool Development for Domestic Animal Species

With the establishment of a genomics infrastructure for a number of the

domestic animal species, the Interagency Working Group is now turning its

attention to its goals in the areas of bioinformatics and functional genomics. To

reiterate, those specific goals are:

• Data management and bioinformatics to specifically support agriculturally

important species. This will support significant improvements in data

management and analysis software, allow greater data accessibility and

secure long term maintenance, increase capabilities to deal with rapidly

accumulating data complexity as databases include functional information,

and provide more powerful tools to mine large genomes (individually and

comparatively).

• Functional genomics to specifically investigate agriculturally important

species. An increase in data for livestock genomes requires concomitant

investment in functional genomics to support genome annotation, the study

of gene regulation and expression, and species evolutionary relationships.

Researchers will have access to individual genes, which can be cloned and

characterized, the ability to scan entire genomes for specific functions, and

be able to gain new insights from comparisons to other genomes.

Quantitative trait loci will be accessible on a gene level, leading to studies

that will elucidate characteristics such as food productivity and disease
resistance and will lead to the ability to manipulate those traits more quickly

and effectively.

USDA is planning a workshop be held in Washington, DC on September 22-23,

2004 to specifically develop a road map for addressing the infrastructure needs

in domestic animal bioinfomatics and functional genomics. This workshop will

bring together leaders from the domestic animal genomics research

community with leading authorities from the human and model species

communities to flesh out this plan. The resulting white paper report will be

presented to the IWG for consideration in carrying out its mission to move efforts

forward in these areas.

Development of Broad-Based Functional Genomics Programs in

Domestic Animal Infectious Disease

One of the most important potential applications of domestic animal genomics

is in the area of infectious animal disease. Recent attention on disease

outbreaks with potential human impact, such as the avian flu outbreak in Asia,

North America, and Europe, and prion diseases such as BSE in cattle, scrapie in

sheep and chronic wasting disease in elk and deer, have accentuated the

need for better understanding of the genomes of both host and pathogen.

Genomics offers the opportunity to better characterize genetic susceptibility to

threatening diseases, particularly those transmitted between humans and

animals. With the completion of annotated genome sequences for the major

domestic animal species, the opportunities to pursue these genomics

approaches are at hand.

In the coming year, the question of what will be required for the publicly funded

research community to develop broad-based domestic animal genomics

research programs to address these critically important animal disease and

biosecurity issues needs to be addressed. This is related to the Presidential

Directive HSPD-9 which calls for a national plan for protection of agricultural

interests within Homeland Security.

Expanding the Genomics Infrastructure to Include Additional Species

Expanding the genomics infrastructure beyond the major domestic animal

species focused upon in the IWG’s initial efforts (chicken, cow, pig, dog,

honeybee) is a major goal in the coming year. Efforts are underway in a

number of other species to develop community resources in the public domain

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 23
24 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK

including BAC maps and EST collections as well as draft genome sequence

assemblies.

The Department of Energy’s Joint Genome Institute at Walnut Creek, California

recently announced that it will accept white paper proposals for whole

genome shotgun sequencing through their Community Sequencing Program.

A number of species of interest to the IWG were submitted including the

channel catfish, rainbow trout, and Pacific oyster.

While not a domestic animal, a mammal of considerable interest to marine

mammologists is the dolphin. Efforts in the coming year by the Office of Naval

Research are seeking to launch a dolphin genomics effort.

The sheep genomics community has recently launched an effort to build a

comprehensive BAC map of the sheep genome, working with the Children’s

Hospital of Oakland, Oakland, California. The domestic cat also continues to

be rated at a “Moderate” priority for sequencing by NHGRI.

Does Genomics Technology Offer the Solution for Animal Traceability and

a National Animal ID System?

As described earlier in this report, DNA genotyping was used in the recent U.S.

BSE crisis through its use to verify the Canadian origin of the Washington state

BSE index cow. Almost immediately following the discovery of this case, the

Secretary of Agriculture directed the establishment of a national animal ID

system to allow full traceability of animals in such biosecurity events in the

future. Planning for a national animal ID system to allow traceability was

already well underway, however.

In October of 2003, the U.S. Animal Identification Plan (USAIP), developed under

the facilitation of USDA’s Animal and Plant Health Inspection Service, was

endorsed by the U.S. Animal Health Association. While the USAIP lays out the

basic plan for a national animal identification system, with the goal of allowing

traceability of an animal within 48 hours of a biosecurity breach, it does not

stipulate the platform for the system. DNA genotyping has high potential for

providing such a platform.

By increasing the genotyping system used by USDA to verify the parentage of

the BSE index cow in 2003 from 32 to 45 SNPs, the discrimination power can be

raised to a level that allows the unique identification of any animal drawn

randomly from the cattle population, although allelic frequencies of additional
SNPs must be validated across additional industry breed populations. Currently,

an industry collaborator has moved the SNP battery to include 47 SNPs (38

highly informative SNPs, 7 Brahman-specific (i.e. Indicus) SNPs and two sexdetermining SNPs).

The application of genomic technology to livestock improvement and

biosecurity is beginning to occur. Several DNA diagnostic tests are now

commercially available in the public domain with a number under industry

developmental testing. An even greater number of markers are routinely being

used within private industry, particularly in the case of swine. The number of

DNA diagnostics is expected to increase exponentially with the release of

annotated whole genome sequence data for chicken, cattle, and swine within

the next few years, the increase in technologies allowing clearer analysis of

gene function and regulation (microarrays, serial analysis of gene expression,

RNAi, etc), and the integration of genetic and physical maps for these species

(integration of linkage, radiation hybrid, and BAC maps). Such DNA diagnostics

will allow the determination of DNA genotypes of individuals for both genetic

improvement and precision management applications, including prevention of

risk of disease outbreak.

The national animal ID system could be the vehicle to allow the widespread use

and adoption of DNA-based management systems. The determination of a

unique animal ID, based upon the animal’s DNA profile for a pre-determined

SNP battery, could serve two purposes. First, unique identification of an animal

is easily accomplished. Secondly, the SNP battery can be designed to

simultaneously genotype economically important diagnostics for genetic and

management purposes for those who wish to have access to such information.

Previous use of DNA genotyping for animal identification has been almost

exclusively for parentage verification. Widespread implementation of the

technology has been very slow, primarily due to the high cost ($25 per sample),

in using microsatellite-based genotyping systems. Economic modeling in beef

cattle systems has shown that the cost of this technology must be in the $5 to $7

per head range to be practical. Higher volume would be expected to

substantially reduce per head cost.

Current genotyping platforms have achieved remarkable throughput and costs

have lowered dramatically in recent years. Current estimates range from $.25

to $.50 per SNP in high volume operations. Using a mass spectrometry platform,

most companies estimate that the lower end of this cost range is feasible. Thus,

a DNA genotyping system employing 40 markers could be commercially

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 25
available for $10 or less in high volume systems, as would be the case in a

national animal ID scheme. Several commercial vendors are attempting to

enter various parts of this type of market.

The practical application of a DNA-based system would operate in the

following manner:

• An animal would be sampled for DNA simultaneously when a unique bar

code is assigned to it as its individual animal ID (USAIN in the USAIP). Tagging

systems allowing such to occur using electronic ID (EID) are available in the

marketplace which allow retrieval of DNA from blood spotted to a card at

the time of tagging, already cross-referenced to the bar code of the tag.

• The DNA genotype for the animal would be determined and entered in the

national database by cross-reference to the bar code.

• If the animal was involved in a situation requiring trace-back and verification,

DNA would always be available, through to the retail cut basis, to do so.

• If external identification for an animal was lost, the animal could be easily regenotyped to determine its original USAIN.

• If the DNA genotype information was desired by the owner of the animal, the

commercial vendor could make such available on a fee basis, allowing the

offsetting of a portion of the genotyping cost of the national animal ID

system.

The application of genomics-based technology in a national animal

identification system will be carefully evaluated within federal research

programs in the coming year.

26 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
VI. Appendix

URLs for useful information on domestic animal genomics:

National Science and Technology Council homepage:

http://www.ostp.gov/NSTC/html/NSTC_Home.html

USDA Research, Education, and Economics homepage:

http://www.reeusda.gov/ree/

NSF Directorate for Biological Sciences homepage:

http://www.nsf.gov/bio

DOE Office of Science homepage: http://www.sc.doe.gov/

National Human Genome Research Institute homepage:

http://www.nhgri.nih.gov/

DbEST (EST database at the NCBI): http://www.ncbi.nlm.nih.gov/dbEST/

Online Mendelian Inheritance in Man Database at NCBI:

http://www.ncbi.nlm.nih.gov/Omim

Genbank at NCBI: http://ww.ncbi.nih.gov/Genbank

National Center for Biotechnology Information’s Map Viewer:

http://ww.ncbi.nlm.nih.gov/mapview

European Molecular Biology Laboratory’s Nucleotide Sequence Database, EMBL-Bank:

http://ww.ebi.ac.uk/embl/index.html

DNA Data Bank of Japan, DDBJ: http://ww.ddbj.nig.ac.jp

University of California, Santa Cruz’s Genome Browser:

http://genome.ucsc.edu/cgi-bin/hgGateway

European Bioinformatics Institute’s Ensembl: http://ww.ensembl.org

Washington University Genome Sequencing Center:

http://genome.wustl.edu/projects

Broad Institute, MIT: http://www.broad.mit.edu/

Baylor College of Medicine Human Genome Sequencing Center:

http://hgsc.bcm.tmc.edu

ChickNet: http://chicken-genome.org

Alliance for Animal Genomics Research:

http://eversoleassociates.com/alliance

Center for Integrated Animal Genomics, Iowa State University:

http://ciag.iastate.edu

Biotech Center, University of Illinois: http://www.biotec.uiuc.edu

USDA Agricultural Research Service: http://www.ars.usda.gov

USDA/ARS U.S. Meat Animal Research Center:

http://www.sol.marc.usda.gov/

USDA/ARS Beltsville Animal and Natural Resources Institute:

http://lpsi.barc.usda.gov/

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 27
Acknowledgements

The Interagency Working Group on Domestic Animal Genomics

acknowledges the assistance of the following individuals in the preparation

of this report:

Jane Peterson, NIH/NHGRI

Deb Hamernik and Muquarrab Qureshi, USDA/CSREES

Kevin Hackett, Steve Kappes, Gary Rohrer, and Warren Snelling, USDA/ARS

Larry Schook, University of Illinois

Avital BarShalom, OSTP (previous IWG Executive Secretary)

Ruth Coy, Jody Shuart, and Mina Chung, USDA/ARS Information Staff

Photo Credits

Cover Left to right: Piglets, photo by Scott Bauer, ARS image number K9455-1;

bee, photo by Jack Dykinga, ARS image number K5400-1; chicks,

photo by Keith Weller, ARS image number K3627-16; Jack Russell terrier,

photo by Dave Hodge; and sheep, ARS image number K4166-5.

Page vi Sheep graze near Odell Lake at the U.S. Sheep Experiment

Station in the Centennial Mountains of southwestern Montana, photo

by Scott Bauer, ARS image number K5629-2.

Page 1 Jack Russell terrier, photo by Dave Hodge.

Page 2 Chicks atop a picture of a genetic map of a chicken, photo by Peggy

Greb, ARS image number K8764-1.

Page 3 Cat/Human Parallel Radiation Hybrid Map. National Cancer Institute.

Page 4 Entomologist Steve Sheppard prepares an agarose gel to be used in

separating honey bee DNA fragments, photo by Scott Bauer, ARS

image number K5799-1.

Page 5 Differences between European and Africanized honey bees can be

seen in this DNA sequencing gel being read by microbiologist Hachiro

Shimanuki and geneticist Cristina Arias, photo by Scott Bauer, ARS

image number K5764-16.

Page 6 Cattle feeding, photo by Brian Prechtel, ARS image number K5643-20.

Page 7 A small dairy farm in western Maryland, ARS image number K8502-1.

Page 8 Calf, photo by Scott Bauer, ARS image number K9481-1.

Page 9 Goat, photo by Scott Bauer, ARS image number K8595-9.

Page 10 Cat on human conserved synteny map, National Cancer Institute.

28 COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK
Page 11 White turkey, photo by Scott Bauer, ARS image number K7043-16.

Page 12 Chicks, photo by Keith Weller, ARS image number K3627-16.

Page 14 Bee, photo by Jack Dykinga, ARS image number K5400-1.

Page 15 Red jungle fowl, photo by Bill Payne.

Page 16 Boxer, Whitehead Institute/MIT Center for Genome Research.

Page 17 Sheep, ARS image number K4166-5.

Page 18 USDA ceremony launching the bovine genome sequencing project,

Washington, DC, December 12, 2003. Left to right: Joseph Jen,

Under Secretary, REE, USDA; Wayne Roberts, Budget Director, State of

Texas; Hon. Ann Veneman, Secretary of Agriculture, USDA; Francis

Collins, Director, Human Genome Research Institute, NIH; Kathie

Olsen, Associate Director, OSTP; and Martin Godbout, President and

CEO, Genome Canada. Photo by USDA Communications Office.

Page 19 Hereford bull, photo by Mike MacNeil.

Page 20 Piglets, photo by Scott Bauer, ARS image number K9455-1.

Page 21 Cattle, photo by Keith Weller, ARS image number K4328-8.

Page 22 Lamb, photo by Karen Carpenter, Texas A&M University.

Page 23 St. Croix sheep, ARS image number K3719-1.

Page 24 Siamese cat, photo by Ann Carlson.

Page 25 Dairy cow, photo by Keith Weller, ARS image number K5176-3.

COORDINATION OF PROGRAMS ON DOMESTIC ANIMAL GENOMICS: THE FEDERAL FRAMEWORK 29