Gene-seekers Look at Nature-Nurture in
Diseases
By Audrey Huang Johns Hopkins Medicine
Johns Hopkins'
McKusick-Nathans Institute of Genetic Medicine is one
of two gene-hunting
facilities in the nation to win a new $11.7 million
four-year federal grant to rigorously sort out how
such environmental factors as diet, exercise, stress and
addictions interact with people's individual
genetic makeup to affect their risk for disorders as
wide-ranging as cancer, diabetes, tooth decay and
heart disease.
The Johns Hopkins
Center for Inherited Disease Research, a part of the
McKusick-Nathans
Institute of Genetic Medicine, along with the Broad
Institute of MIT and Harvard, will use advanced
genotyping technology to identify specific genetic
differences between those with and those without
particular medical conditions by searching their entire
genomes. They will partner with eight teams of
scientists from academic institutions around the country
who have studied large numbers of people to
identify gene and environment interactions in a variety of
common disorders. Scientists at the
University of Washington will coordinate the efforts of the
Genes and Environment Initiative
consortium.
"Geneticists have known for some time that common
diseases are the outcome of interactions
between the genes we're born with and how they respond to a
lifetime of exposure to the environment
around us," said David Valle, director of the Center for
Inherited Disease Research and the Henry J.
Knott Professor and Director of the Institute of Genetic
Medicine. "But now that advances in
technology and science have given us the tools to rapidly
search whole genomes and to enumerate the
millions of specific genetic differences between
individuals, we can compare these differences
between people who have a disease and those who do not.
What is exciting about this project is that
the investigators will also be keeping track of differences
in environmental exposures. In this way, we
will begin to learn how genetic variation, lifestyle,
behavior and other environmental variables
contribute to health and disease."
The Center for Inherited Disease Research, established
in 1996, brings together scientists who
specialize in genetics, genomics, molecular biology,
statistics, medicine and bioinformatics to identify
genes that contribute to so-called complex disorders,
defined as common human diseases known to
result from variations in many of our 22,000 genes as well
as such external, environmental risk factors
as smoking, air pollution, infections, drugs and
nutrition.
In 2003, the center and the Institute of Genetic
Medicine's Genetic Resources Core Facility
teamed up to offer high-throughput genotyping as well as
other services necessary for genomewide
association studies, including DNA isolation, amplification
and quantitation, which will be offered as
part of the Genes and Environment Initiative program.
Among other approaches, Hopkins' CIDR specialists and
the members of the GEI consortium will
overlay individual variations in genomes with individual
environmental histories to find patterns of
associations and hunt down "connections" that occur most
frequently in patients compared to a control
population.
Elias A. Zerhouni, director of the National Institutes
of Health, said, "Genomewide association
studies have proven themselves to be powerful tools for
discovering the genetic contributions to
common diseases. Early findings from such studies have
identified new genetic variants contributing to
a higher risk of common diseases such as prostate cancer,
diabetes and heart disease, but
researchers have only scratched the surface," he said. "The
genetic studies being funded today will
identify many novel genetic variants contributing to an
increased risk for these health conditions."
Related Web sites
McKusick-Nathans Institute of Genetic Medicine
The Center for Inherited Disease Research at Johns
Hopkins
National Human Genome Research Institute
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2007
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