The Human Genome Sequence: The Human Genome II: Sources of Genetic Variation

The simple property of base pairing is central to a rapidly evolving DNA technology with which researchers can now directly examine the genetic structure of individual human beings to search for sequence variations that are correlated with specific disease states. The ultimate goal of this research is to find the gene variants that cause or influence vulnerability to disease. Techniques such as Southern blot analysis and restriction fragment length polymorphism analysis have been used to detect variations in individual DNA. Now a more efficient technique, polymerase chain reaction (PCR), is universally used. PCR copies specific regions of human DNA using a temperature-activated enzyme (Taq polymerase) and nucleotide primers matched to the DNA region of interest. After DNA amplification with PCR, the sequence-amplified products can be analyzed for single-base variations or polymorphisms (from the Greek, meaning “multiple forms”). All people carry innocuous sequence variations in their DNA; these variations occur at a rate of approximately one for every 1,000 bases. One of these sequence variations could be associated with risk for a disease. Techniques for identifying the millions of variations of single nucleotides (called single nucleotide polymorphisms [SNPs]) in human DNA are being used to catalogue the extensive variation in the human genome. The ultimate goal of this effort by the Human Genome Project, involving an international network of cooperating scientists, is to identify, localize, and determine the sequence of all genes and their rates of variation.