In the summer of 2000, scientists around the world
cheered as the effort to unravel the mystery of the human
genome reached a milestone—a completed draft of the
human genome sequence. The sequence is a set of
instructions that determines individual characteristics
ranging from the cosmetic, such as hair and eye color, to the
medically important, such as susceptibility to disease and
response to treatments.
The challenge for scientists is that although they have sequenced one human genome, there are approximately
six billion people in the world, all with different physical characteristics and genes. In a comparison of two
random people, 99.9 percent of their genetic sequence is identical. Individual differences, then, are defined by
this distinctive tenth of a percent of the genetic sequence.
The study and use of information about human genetic variation are becoming increasingly important now
that the genome is sequenced. Individual genetic differences are very important because by understanding
the differences, scientists and physicians will be able to identify genes associated with diseases, develop new
drugs to fight disease and design better treatments for individual patients. Several pharmaceutical compa-
nies promote the idea of “personalized medicine,” resulting from the integration of genomics and drug
discovery and design. This has led to a new field known as “pharmacogenomics.”
The most common type of genetic variation is single nucleotide polymorphisms, or SNPs. In the human
genome, there are millions of SNPs.
Among other things, locating SNPs will ultimately help physicians prescribe the most effective treatments for their
patients. Every year approximately two million people have adverse reactions to drugs, resulting in nearly 100,000
deaths. Many of these deaths could be avoided if doctors knew more about the person’s genetic background.
Specifically, physicians would be able to treat patients more effectively if they had an understanding of the genetic
variations that affect drug metabolism. With this information, the physician could prescribe a treatment that would
be maximally effective and less likely to produce an adverse reaction in that specific patient.
Researchers at Los Alamos National Laboratory have developed a novel way to search genetic sequences for
targeted subsets of the many millions of SNPs. Researchers Scott White, John Nolan and Hong Cai have collaborated to create a method of analyzing SNPs by putting synthetic DNA probes on tiny plastic microspheres for
the purpose of studying them with a fluorescent measurement instrument called a flow cytometer. The benefit
of the Los Alamos system is that it can analyze a very large number of samples quickly, inexpensively and
relatively easily, in comparison to other methods of analysis.
One of the first groups of SNPs that the team studied identified a genetic marker for beryllium disease, an illness that can affect nuclear and industrial workers who handle this metal. Thanks to the development of the new SNP analysis method, Los Alamos researchers have developed a test to identify specific individuals who are at risk for
development of the disease.
Those workers who are most
susceptible can then be advised of their increased risk, and overall safety
of the workforce can be improved.
Beyond beryllium disease, the researchers are addressing the role of
genetic variation in susceptibility to cancer and response to drugs. They
also are working to develop a better understanding of human history
and population structure. In addition, these researchers are applying
this technology to the study, detection and identification of human
pathogens, including the influenza virus and pathogenic bacteria such
as E. coli and other food-borne pathogens.
The Los Alamos team has filed patent applications on its process and
is working closely with a commercial
partner to bring its SNP analysis
method to the marketplace. The team
also has had interest from pharmaceutical companies, clinical diagnostic
laboratories and others.This new
technology is being implemented in
Los Alamos' Bioscience Division facility
for the large-scale analysis of genetic
variation. The facility will enable
Laboratory researchers and academic
collaborators to access this powerful
new tool to address critical issues that
include human health and disease.
The Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time.