Making SNPs Make Sense

Scientists are identifying, cataloging, and studying small genetic variations among humans that will lead to more specialized and effective medical treatments. What do these variations look like, and what exactly makes them informative?

Researchers look for one or more single nucleotide polymorphisms (SNPs; pronounced "snips"). SNPs are single-nucleotide substitutions of one base for another that occur in more than one percent of the general population.

The challenge for scientists is to identify SNPs that correlate with a particular effect in patients. Reliable SNPs could serve as predictive markers that inform our decisions about numerous aspects of medical care, including specific diseases, effectiveness of various drugs and adverse reactions to specific drugs.

This pharmacogenetic approach could save time, money, and discomfort for millions of patients through accurate diagnoses and matching patients with appropriate medicines.

Scientists approach the problem of identifying, cataloging, and characterizing SNPs in two main ways:

• Genomic approaches. This approach is used by scientists who want to see the big picture. Several large-scale projects have combined the efforts of many institutions to identify and catalog all of the SNPs in the 3-billion-base pair human genome. Each project involves hundreds of scientists, who compare the genomes of numerous individuals to identify the differences. These comparisons require a lot of computer-powered data analysis. As they work, scientists sort and catalog their results in databases that are available to anyone over the Internet, including other scientists and you.
• Functional approaches. This approach is used by scientists who are interested in a particular disease or drug response. The biological processes involved in diseases and drug responses are controlled by the activities of many genes. Scientists interested in a particular process select genes known to be involved in the process and examine them in people who have a response or disease, as well as those who don't. By comparing people's DNA sequences, scientists can identify SNPs that correspond with a particular function or response.

SNP (pronounced "snip") stands for Single Nucleotide Polymorphism. SNPs are single-nucleotide substitutions of one base for another. Each SNP location in the genome can have up to four versions: one for each nucleotide, A, C, G, and T. A SNP and its distribution in a population might look like the images below and to the left.

Not all single-nucleotide changes are SNPs, though. To be classified as a SNP, two or more versions of a sequence must each be present in at least one percent of the general population.

SNPs occur throughout the human genome—about one in every 300 nucleotide base pairs. This translates to about 10 million SNPs within the 3-billion-nucleotide human genome.

If you know what a point mutation is, then the description of a SNP might sound similar. True, both are single-nucleotide differences in a DNA sequence, but SNPs should not be confused with disease-causing mutations. The image to the left shows some tell-tale differences:

First, to be classified as a SNP, the change must be present in at least one percent of the general population. No known disease-causing mutation is this common.

Second, most disease-causing mutations occur within a gene's coding or regulatory regions and affect the function of the protein encoded by the gene. Unlike mutations, SNPs are not necessarily located within genes, and they do not always affect the way a protein functions. SNPs are divided into two main categories:

SNP and Haplotype Mapping Information and Databases

• SNPs: Variations on a Theme, a Science Primer from the National Center for Biotechnology Information (NCBI).
• dbSNP, a database of human SNPs, from the National Center for Biotechnology Information (NCBI).
• The International HapMap project, a partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States.
• SNP Scoring, from PerkinElmer, Inc. explains several SNP detection techniques