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Physiologic and behavioral stress responses have been characterized, and pain assessment tools are available to guide clinical management. Serious consequences may result from insufficient pain management in premature infants. Inadequately managed pain during the critical period of brain development may permanently compromise neuronal and synaptic organization. Sustained pain may predispose the immature infant to significant adverse neurologic events, such as IVH and long-term neurodevelopmental and cognitive sequelae (37:Mevacor).

Advances in the molecular genetics laboratory have led to DNA diagnostic techniques for many single-gene conditions. These methods can be direct or indirect. Direct methods evaluate the DNA for specific mutations. To use a direct method, the gene must have been identified and an efficient technique for identification of the mutation must be available. For example, sickle cell disease is due to a single nucleotide substitution at the sixth codon of the ОІ-globin chain. The mutation changes codon 6 from guanine-adenine-guanine, which codes for glutamic acid, to guanine-thymine-guanine, which codes for valine. Early on, this single nucleotide change was shown to be detectable using a RFLP. The restriction enzyme cuts the normal DNA sequence, but the mutation changes the cut site so it is no longer recognized by the enzyme, allowing diagnosis to be made by examining the size of the resulting DNA fragments (24:Mevacor).

Changes in genetic material are called mutations. They can be neutral in effect, disease producing, or rarely protective. Polymorphisms are variations in the DNA sequence that occur at a frequency of more than 1%. These mutations are less frequent in coding regions of the gene and are much more commonly found in introns or between genes. Different types of DNA variations include restriction fragment-length polymorphisms (RFLPs) (5), single nucleotide polymorphisms (SNPs) (6), variable number of tandem repeat polymorphisms (7), and microsatellite markers. SNPs are the most common of these, occurring as often as once in every 100 to 300 base pairs. Typically, polymorphisms do not produce disease, although in some cases, a polymorphism can increase a person’s disease susceptibility. Polymorphisms are helpful for following the inheritance of a nearby gene through families, as well as for studying the genetic susceptibility to certain complex diseases (8).