The Bovine Genome Sequencing Project
The major aim of the Bovine Genome Sequencing Project (BGSP) is to provide researchers throughout the world with comprehensive bovine DNA sequence information that will accelerate progress toward basic and applied outcomes in the livestock sciences. The project, which costs US $53 million, is managed by an international consortium headed by Dr Stephen Kappes (USDA). Dr Richard Gibbs (Baylor College of Medicine) leads the sequencing effort. The bovine genome is slightly smaller in size than the human genome, which contains approximately 3 billion DNA base pairs.
In addition to helping medical researchers learn more about the human genome and thereby develop better ways of treating and preventing disease, the bovine genome sequence will serve as a tool for agricultural researchers striving to improve health and disease management of cattle and enhance the nutritional value of beef and dairy products.
Sequencing of the bovine genome began in December 2003. The breed of cattle selected for the bulk of the sequencing project was Hereford, which is used in beef production. A high-resolution photo of the Hereford cow, named L1 Dominette 01449, whose DNA was sequenced is available here.
The BGSP has three major technical objectives.
(i) to produce a ‘draft’ bovine sequence assembly.
A 7-8X ‘draft’ assembly of the bovine genome sequence will be released in 2006. A 3X assembly is already publicly available. A 7-8X coverage means that on average each DNA sequence region is sequenced 7-8 times. This strategy minimises gaps in the sequence and provides high quality DNA sequence information. The size of the bovine genome is thought to be approximately 2.7x107 bp in length. This sequence information is being produced by the Baylor College of Medicine, Human Genome Sequencing Centre, Texas and is led by Richard Gibbs and George Weinstock.
(ii) to produce 10,000 full length mRNA sequences
Additional research aimed at uncovering more detailed information about individual bovine genes - a process referred to as full-length cDNA sequencing - is being conducted by a team led by Dr Marco Marra, at the British Columbia Cancer Agency in Vancouver.
(iii) to discover at least 100,000 Single Nucleotide Polymorphisms
Individual animals differ from others at many regions in their genomes. The most frequent differences are single nucleotide polymorphisms (SNPs). These define the differences between animals and breeds within a species. SNPs are very valuable as they provide molecular tools that allow selection of animals with high production merit.
The BGSP has identified approximately 120,000 SNPs by
comparing the genome sequence of L1 Dominette 01449 with
low levels of sequence from animals representing 6
additional breeds - Holstein, Angus, Jersey, Limousin,
Norwegian Red and Brahman. In addition, another process may
have identified as many as 2 million SNPs. SNP discovery
was undertaken at the Baylor College of Medicine, Human
Genome Sequencing Centre, Texas. This effort is led by
Richard Gibbs and George Weinstock.
A significant SNP validation effort in defined populations
of cattle representing approximately 14 breeds is currently
in progress. The aim of this study is to understand the
relatedness between these populations. This aspect of the
research involves a large group of scientists from many
countries. The project is referred to as the Bovine HapMap
Project.
The Consortium
Funding for this project has been provided
by: the National Human Genome Research Institute (NHGRI U54 HG003273), which is part of
the National Institutes of Health (NIH) ($25 million); the U.S.
Department of Agriculture's Agricultural Research
Service and Cooperative State Research, Education, and
Extension Service (USDA ARS Agreement No. 59-0790-3-196
and CSREES Agreement No.
2004-35216-14163) ($10 million); the State Of Texas ($10 million); Genome Canada through Genome British Columbia ($5 million),
The Commonwealth Scientific and Industrial Research
Organization of Australia (CSIRO) ($1 million); Agritech Investments Ltd., Dairy Insight, Inc. and AgResearch Ltd., all of New Zealand ($1 million); the Kleberg
Foundation; and the National, Texas and South Dakota Beef Check-off Funds ($1
million).
In addition, a large of number of scientists from across
the globe have contributed in many different ways to the
project particularly in the supply of supportive
information. One important contribution has been the
generation of an integrated bovine chromosomal map which
allows placement of the sequence information onto
chromosomes. The BGSP is a project that represents
international cooperation at all levels.
Research that is now possible because of the BGSP
The availability of the bovine
genome sequence provides sequence information on the full
repertoire of bovine genes and thereby provides researchers
with the opportunity to identify genes that contribute to
various traits of interest. For the first time the
activities of all of these genes can be simultaneously
examined in a particular tissue using microarray genechips.
The bovine genome sequence
allows capture of the enormous wealth of human and mouse
genetic and biological knowledge. It also allows better
interpretation of the functions of human genes and in some
instances can provide models of human diseases and thereby
a better understanding of these diseases.
The availability of large numbers of bovine SNPs enables
scans of the genome to be performed to identify favourable
alleles of genes that contribute to desirable phenotypes
eg. more milk, higher quality meat, increased growth,
increased disease resistance and increased feed conversion
efficiency.
The sequence information will allow an understanding of the
genetics that underlies the historical relationship between
man and livestock animals bred for specialised purposes
such as ploughing, milk and meat production and tolerance
to tropical diseases.
The BGSP will also help the understanding of how ruminants
efficiently transform low energy pasture into high energy
milk and meat products.
The deliverables in the short and longer
term.
The major short term deliverable is the sequence
information itself. Much of this is already available but
the assembled information is due in 2006. Considerable use
has been made of the fragmentary sequence data that has
been generated over the last 2-3 years.
Preliminary SNP information has been used by several groups
for whole genome scans of production animals to identify
genetic polymorphisms associated with production traits.
These genetic polymorphisms will be used in selective
breeding programs.
Industry outcomes will result from an acceleration of
current research and development but importantly the BGSP
will be the engine that drives the creation of innovative
new products and solutions to current intractable
production problems. The industry outcomes largely fall
under the areas of production, product quality and novel
products, health and disease resistance, reproduction,
bioactives, and welfare (livestock and human). The economic
benefits will largely be targeted at production issues and
as a result it is anticipated that there will be increased
producer profitability. There is also considerable scope
for the production of high value-added products whose
benefits will be captured in the processing sector. One of
the most significant long-term benefits will be the
maintenance of an environmentally and economically
sustainable industry.
The bovine genome sequence will be a pivotal resource that
will have impact on the livestock industry for many
decades. DNA markers for some desirable production traits
such as marbling and tenderness are already available and
many more are being developed.
The following is a list of anticipated long term industry
benefits arising from the application of genome sequence
knowledge.
-
Acceleration of marker assisted breeding for enhancement of
desirable production traits eg. growth rate, meat yield,
marbling, tenderness, milk protein and fat quantity and
composition, reproductive performance; identification of
elite individuals, behavior;
- Perfect gene markers for desirable
production traits; especially traits difficult and costly
to measure eg. reproduction, survival, traits with low
heritabilities, “death limited” traits (carcass
quality), feed conversion efficiency, disease resistance;
- Increased accuracy of selection;
- Trace-back capability; parentage and
family assignment;
- Production of disease resistant animals;
improved disease diagnosis; early detection of
predisposition to disease; identification of disease
susceptible sentinel animals;
- Production of high quality animals
adapted to specific local environments;
- Responsiveness to intervention (eg.
increased vaccine responsiveness; shorter cycles for
vaccine development); better risk assessment and
management;
- Decreased reliance on antibiotics and
growth promotants;
- Bioactive design and delivery
(nutrition, therapeutic and pharmacological interventions
for growth, product modification, customised interventions
for specific breeds);
- Focus on environmentally sustainable
production - smaller environmental footprint of the
industry (eg. increased feed conversion efficiency, faster
growth rates, higher retail yield, increased rumen
function, reduced demand for land for feed production);
- Better animal welfare (less susceptible
animals to stress, heat, cold, handling, disease);
- An ability to produce milk made to order
for specific industries eg cheese production.
- Indirect outcomes for other ruminants
eg. the bovine genome sequence will have major implications
for sheep production issues;
- Sheep producing higher quality wool and
cattle producing higher quality meat and milk;
Contact person:
Dr Ross Tellam
Senior Principal Research Scientist
CSIRO Livestock Industries
306 Carmody Rd
St Lucia 4067
QLD
Australia
07 31242476
Ross.Tellam@csiro.au
Links
White paper proposing the sequencing of
the bovine genome
A high resolution photo of L1 Dominette:
01449
Sequence information from the Bovine
Genome Sequencing Project:
Researchers can also access the sequence data through the
following public databases: GenBank (www.ncbi.nih.gov/Genbank or http://www.ncbi.nlm.nih.gov/genome/guide/cow/)
at NIH's National Center for Biotechnology Information
(NCBI), EMBL Bank at the European Molecular
Biology Laboratory's Nucleotide Sequence Database and
the DNA Data Bank of Japan. The data will
also be viewable through NCBI's Map Viewer, UCSC Genome Browser at the University
of California at Santa Cruz and the Ensembl Genome Browser at the
Wellcome Trust Sanger Institute in Cambridge, England.
