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The
Genome Bioinformatics Group
at UC Santa Cruz played a
pivotal role in bringing this
extraordinary life script
into the light of science.
Its brainchild, the UCSC Genome
Browser, provides a web-based
"microscope" for
exploring the human genome
sequence and is used daily
by thousands of biological
and biomedical researchers
throughout the world.
The
Genome Bioinformatics Group
aids the worldwide scientific
community in its challenge
to understand the vast amounts
of information contained in
the genome sequence, to probe
it with new experimental and
informatics methodologies,
and ultimately to decode the
genetic program of the cell,
laying out the plan for the
complex pathways of molecular
interactions that it orchestrates.
DISCOVERY
AND ANNOTATION
While the sequence of the
genome is now available, our
ability to decode that sequence
and tap into the wealth of
information it holds is still
quite limited. Today the UCSC
Genome Bioinformatics Group
works to make the human genome
sequence even more useful
for science and medicine by
identifying and annotating
its key functional elements
in such a way that they are
easily accessible to researchers.
This process of discovery
and categorization is a critical
step toward fully understanding
the workings of the human
genome, a project that will
occupy science and medicine
for many years.
Genome sequences are difficult
to read, because they consist
of letter strings with no
breaks or punctuation. The
example below contains 7 different
letters (genomes contain only
4). Can you understand what
it is saying?
THATTHATISISTHATTHATISNOTISNOTISTHATITITIS
With word breaks and punctuation,
it starts to make sense:
THAT THAT IS, IS. THAT
THAT IS NOT, IS NOT. IS THAT
IT? IT IS!
To facilitate the annotation
process, Jim Kent and the
growing UCSC Genome Bioinformatics
Group constructed the UCSC
Genome Browser. This web-based
tool serves as a multi-powered
microscope to view all 23
chromosomes of the human genome.
The coarse-level view shows
early chromosome maps as determined
by electron microscopy, then
the browser drills down to
levels of increasing detail,
focusing first on chromosome
bands, then on gene clusters
(showing known genes—mostly
those linked to diseases),
then single genes, then components
of genes, and finally on the
nucleotides—the As,
Cs, Gs, and Ts that make up
the genome alphabet.
Not only does the browser show
the genome sequence, it delineates
known areas of the genome
and offers supplementary information
about the genes—in effect,
providing the word breaks
and punctuation. The UCSC
browser brings the genome
sequence to life by aligning
relevant areas with experimental
and computational data and
images generated in the last
decades by scientists from
around the world. It also
links to databases throughout
the world, giving researchers
instant access to deeper information
about the genome.
The UCSC Genome Browser is
available worldwide without
charge, and the web site receives
about 4,000 visitors per day.
In a usual week, the visitors
generate 1 million page requests
as they explore the genome.
The site has logged visitors
from 44 countries throughout
the world.
Since the first assembly of
the human genome, the UCSC
group has added a growing
number of species to the UCSC
Genome Browser, including
roundworm, puffer fish, chicken,
mouse, and chimpanzee. Interspecies alignments allow researchers to compare human genes to similar genes in other species. New features, such as VisiGene, an image library that corresponds to the genome data, expand the usefulness of the browser. Along
with researchers worldwide,
UCSC participates in projects
to compare genomes of various
species as a way to better
understand gene function and
the process of evolution.
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COMPARATIVE GENOMICS
Besides developing, supporting, and continuing to improve the genome browser, the UCSC Genome Bioinformatics Group conducts research into the functional elements of the human genome that have evolved under natural selection. The UCSC Genome Browser allows rapid comparisons between species, which can lead to many different types of new discoveries: |
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Searching
the human genome for sequences that match those
with known functions in other organisms can lead
to new human gene discoveries.
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The
molecular genetics behind disease development and
progression in model organisms can be leveraged
to discover potential disease-related genes in
humans, moving us closer to diagnostic advances
and targeted treatments.
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We
can reconstruct the evolutionary history of the
human genome by identifying the origins of interspecies
differences and of short segments in the human
genome that have been extremely well-conserved
over millions of years of evolution.
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By
searching for the highly conserved segments in
the human genome— those that are unchanged
from like segments in the genomes of other organisms,
we can begin to understand the essential elements
of the blueprint for life. Researchers suspect
that these highly conserved elements must be essential
to function. Genes make up only a small percentage
of the unchanged elements, suggesting that other
unknown regulatory elements in the genome are also
important for function.
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Searching for genes that have evolved with unusual speed from one organism to another will give clues to essential interspecies differences, such as differences between the human and chimpanzee brain.
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POSSIBILITIES
FOR HEALTH
As we
begin to better understand the molecular mechanisms
responsible for human disease, entire new avenues of
treatments will be possible. We are only now getting
a first glimmer of the molecular functions of a healthy
human cell or organ, and we are still a long way from
understanding the often subtle and complex ways that
these can go awry. Yet knowledge of the human genome
puts us on the brink of a revolution in medicine.
Rather
than relying on trial and error to design and test
new drugs, researchers will increasingly use their
knowledge of the molecular causes of diseases to
design new, targeted therapies. Research based on
genome studies
will also form the basis for new diagnoses and therapies
for human disease that will transform the practice
of medicine in this century.
The UCSC Genome Browser supports the latest endeavor of the National Human Genome Research Institute (NHGRI), a medical sequencing project intended to amass data relating genes to health conditions. This project sets the stage for the time when it becomes affordable for an individual's genome to be sequenced. The information obtained will allow estimates of future
disease risk and improve the prevention, diagnosis, and treatment of disease. The project focuses on rare Mendelian disorders, complex disorders, and normal human variation.
The practice of medicine
will
become much more individualized, with therapies tailored
to be most effective given an individual’s
genetic makeup. Medical tests are already available
to identify individual genetic variations that affect
a patient’s response to commonly used medications.
These tests can allow doctors to avoid adverse reactions
and choose medications appropriate for specific individuals. Someday
we may even be able to repair or replace the disease-causing
genes, re-orchestrating the molecular
pathways needed for health.
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