Molecular biology technician
Renee Godtel prepares bovine
DNA samples for sequencing.
First there was the mapping of the human genome. Then, this spring,
scientists announced they had nearly completed the genome mapping of
the mouse. Now, scientists are in the early stages of mapping the bovine
genome to help produce cattle with improved production traits and to
possibly help in finding cures for human diseases.
The Agricultural Research Service
is part of a group of government and university laboratories from four
continents in the initial stages of mapping the bovine genome. The ARS
research effort is led by Steven Kappes and John Keele of the Roman
L. Hruska U.S. Meat Animal Research Center, in Clay Center, Nebraska.
Kappes is center director, and Keele is an animal scientist.
The project began in spring 2000, when Kappes started contacting labs
from around the world to develop a physical (bacterial artificial chromosomeBAC)
map of cattle. Bacteriaand more specifically, bacterial chromosomesare
used as hosts for pieces of bovine chromosomes. The bacterial hosts
are used to generate many identical copies of a piece, or clone, of
cattle DNA. The BAC map will be a useful tool for identifying genes
that affect production traits in farm animals and an excellent resource
to improve the efficiency of a future effort to sequence the entire
Along with the genomics
group at MARC, animal
scientist John Keele is
part of the team that's
working to produce a
bacterial artificial chromosome
map of the bovine genome.
The first step in the process is to fingerprint individual BAC clones.
Researchers at the British Columbia Cancer Agency Genome Sciences Centre
have been funded to construct a fingerprinted BAC map. A fingerprint
is obtained by cutting DNA from a BAC clone into pieces and separating
the fragments on a gel. The fingerprint pattern of the different fragments
is used to identify overlapping BAC clones. A BAC map is the collection
of overlapping clones that represent the entire bovine genome.
Funding for this part of the project has been provided by USDA-ARS;
the Biotechnology and Biological Sciences Research Council and Roslin
Institute, from the United Kingdom; the University of Alberta and the
Alberta Science and Research Authority, in Canada; and the University
The fingerprinting will be performed on 280,000 BAC clones from two
libraries constructed by scientists at the Children's Hospital Oakland
(California) Research Institute. The first BAC library was constructed
from Holstein bull DNA and the second from Hereford bull DNA. Each BAC
clone contains about 170,000 bases of cattle DNA.
Chemist Tim Smith observes
an automated DNA sequence
instrument, which produces
96 bovine DNA sequences
every 3 hours.
The second step, which can occur simultaneously with fingerprinting,
is sequencing both ends of all 280,000 clones. This work is being conducted
by ARS, the University of Illinois, Texas A&M University, AgResearch
of New Zealand, the Commonwealth Scientific and Industrial Research
Organization of Australia, the Brazilian Agricultural Research Corporation,
and the University of Alberta. The Institute of Genomic Research in
Rockville, Maryland, has been contracted to do some of the sequencing.
The National Institute for Agricultural Research in France is fingerprinting
and end-sequencing clones from a BAC library constructed in their laboratory.
They will combine their information later with the international effort.
Kappes is talking with other organizations to help with the end sequencing.
The scientists will combine the end-sequencing and fingerprinting information
to determine the overlapping BAC clones. Kappes says, "Ideally,
we would like one set of contiguous overlapping clones'contigs'for
each of the 30 chromosomes in the bovine genome. But it's likely that
we'll have gaps between several contigs for each chromosome."
At the British Columbia Cancer
Agency Genome Sciences Center
in Vancouver, Canada, genomics
technologist Pawan Pandoh
prepares BAC fingerprints used
in creating the bovine map.
So far, 249,000 of the 280,000 cattle BAC clones have been fingerprinted,
and the end-sequencing effort is under way. The completion date for
the bovine BAC map is February 2003.
The researchers hope that the next phase of the project will be sequencing
the bovine genome. Kappes and other scientists have sent a proposal
to the National Institutes of Health (NIH) to do this work.
The BAC map alone costs $4.5 million, while NIH estimates it may cost
$100 million to sequence the bovine genome to a finished stage. Kappes
says the effort is expensive, but it will have many tangible benefits.
Scientists from ARS and elsewhere will use the BAC map and sequence
information to improve productivity traits in cattle. This means they
may be able to more accurately select genetically superior animals for
specific needs, such as lean beef, milk production, reduced feed requirements,
and improved health and welfare. This ability would increase the profitability
of beef production. The research should also benefit those who raise
sheep, since the genetic makeup of sheep is very similar to that of
This research may also help the medical community. "As we define
certain biological mechanisms in livestock, the information may benefit
human medicine," says Kappes. "We are currently defining a
genetic mechanism affecting muscling in sheep. This is of specific interest
to research efforts in human medicine because a similar mechanism is
observed in cancer cells."
Not only is there similarity in the DNA sequences of genes in farm
animals and in humans, but also the biological processes are very similar
across species. Eventually, researchers will be able to compare the
human genome to the bovine genome to help determine the function of
genes for both livestock production and human well-being.By David Elstein, Agricultural
Research Service Information Staff.
This research is part of Food Animal Production, an ARS National
Program (#101) described on the World Wide Web at http://www.nps.ars.usda.gov.
Steven Kappes and
John Keele are with the
USDA-ARS Roman L. Hruska U.S. Meat
Animal Research Center, P.O. Box 166, Clay Center, NE 68933; phone
(402) 762-4109, fax (402) 762-4111 [Kappes], phone (402) 762-4251, fax
(402) 762-4155 [Keele].