'SNP'ing' away at human health issues

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.