College Launches New NIH Genomics Center
$18.7 million grant funds one of only seven centers in the nation
USC will expand its role in the fast-paced world of genomics research
this fall with the launch of the USC Center of Excellence in Genomic
Science (CEGS), an interdisciplinary center funded for five years by
$18.7 million in grants from the National Human Genome Research
Institute of the National Institutes of Health (N.I.H.). CEGS will be one of only seven centers in the nation.
The research center and a companion training program will unite
scientists from USC College and the Keck School of Medicine of USC to
develop new methods for studying human genetic variation data that can
be used to identify the causes of diseases and explain differences in
the way people respond to treatments.
The center will enable the USC team, led by University Professor
Michael Waterman, to play a leading role in the effort to turn the
promise of genomics into advances in understanding human disease and
evolution.
“We will focus on developing and testing new experimental and
computational techniques that will increase our ability to find
disease-related genes and extract other useful knowledge from the human
genome,” says Waterman, holder of the USC Associates Chair in Natural
Sciences.
The researchers will play an integral role in the International HapMap
Project, the largest study of human genetic variation ever attempted,
which involves researchers in five nations investigating patterns of
genetic variation in samples from about 300 individuals, including Han
Chinese, the Yorubas in Nigeria, Japanese and U.S. residents of
northern and western European descent.
The long-term aim of the USC center is to build the tools needed to
reveal the causes of diseases influenced by multiple genes, or by a
combination of genes and the environment—such as cancer,
cardio-vascular disease, Alzheimer’s, diabetes, asthma and depression,
which rank among the nation’s biggest killers and most expensive
diseases.
USC is one of only seven universities selected as a site for a national
CEGS program grant and the only one in Southern California. Other CEGS
sites include Yale, Stanford, Columbia and the University of
Washington, Seattle.
“This center grant is a fantastic boost for the molecular and
computational biology program at the College, and for USC genomics
research in general,” says Joseph Aoun, dean of the College and holder
of the Anna H. Bing Dean’s Chair. “This marks the NIH’s recognition
that USC has built phenomenal programs in genomics and computational
biology, and in the application of these fields to the epidemiological
study of disease.”
Understanding Variation
The center’s core research mission focuses on investigating patterns of
human genetic variation. Although all humans are 99.9 percent alike
genetically, slight variations determine differences such as blood type
or eye color. While most variations have no deleterious effects, a few
determine why one person is more likely than another to develop high
blood pressure or breast cancer, or whether a drug will work or cause
unintended harm.
Such differences may stem from a variation as small as one DNA base.
There are millions of these “SNPs,” or single nucleotide polymorphisms,
in the genome. Identifying SNPs important in common diseases has proved
challenging.
Scientists hope to simplify the search by characterizing certain
regions of the genome inherited in big chunks. These “haplotype blocks”
contain many SNPs that are found in unique patterns. The plan is to use
the patterns, instead of individual SNPs, to build a genetic map to
link specific mutations with diseases that would cover the entire
genome. But scientists do not yet know the origins of haplotype blocks
nor how best to use them.
Through a variety of interrelated projects, the USC team seeks answers
to these questions. One will focus on determining how SNPs could be
used as tags to label haplotype blocks. Another will investigate the
quality of human genetic variation data, and look at ways to improve
techniques used to find SNPs. Another group will study biological
processes that have created haplotype block structure.
One hypothesis is that blocks arose from variable rates of
recombination within chromosomes, genetic shuffling that occurs during
fertilization. The USC team will test the idea that the blocks are
chromosome regions with low recombination rates, bordered by areas that
undergo frequent recombination.
If true, team members expect there will be a few types of haplotype
blocks found in people all around the world. If not, and populations
from different geographic regions have block patterns that are
substantially different from other groups, the approach will not be as
powerful as hoped.
The USC team will refine computational methods they develop using real
cancer genetics data collected by the epidemiology group in the medical
school.
“The USC group is one of the world leaders in computational
biology—with a long track record of contributions and a number of young
stars—and in epidemiological disease research,” says David Altshuler of
the MIT/Whitehead Center for Genome Research, who co-chairs the HapMap
analysis group. “Our understanding of how to analyze and utilize human
genetic variation remains in its infancy. [We] will look to USC, along
with others, to develop new methods to interpret genetic variation data
and to apply that data to better understand, diagnose and treat common
human diseases,” he says.
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