Validation of RLB hybridization tests involves retrospective scoring of samples that have been reliably characterized by some other method, most often polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Polymerase chain reaction-restriction fragment length polymorphism takes advantage of base-pair changes that create or interrupt palindromic restriction-enzyme recognition sites. Although this is a simple approach, restriction-enzyme cleavage is limited to linkage analysis of polymorphic restriction sites and to situations in which the mutation serendipitously creates or disrupts a restriction site. It also requires that the amplification reaction produce a unique product fragment. For historical reasons, PCR-RFLP remains the gold standard for clinical diagnosis of point mutations. New technologies for mutation detection are often compared against it. In 1999, polymorphisms discovered in the binding site of PCR primers within the hemochromatosis locus changed clinical practice by exposing the myth that PCR-RFLP is the most reliable genotyping technique (see Ref. [1] for details).

A statistical rating of analytical specificity provides a measure of how often a test is negative when a mutation is not present. This amounts to measuring the number of false negatives, or mutations missed. This statistic is expressed as a percentage of mutations missed over all other classes of test outcome. The analytical specificity of

RLBs is extremely high. Palomaki et al.[2] found the analytical specificity of cystic fibrosis tests conducted in the United States to be 99.4% (95% CI 98.7-99.9%) after removing challenges involving AI507. The few exceptions to the rule of high specificity are discussed in ''Limits and Clinical Applications'' below. Clinical specificity is the quotient of normals (or noncarriers) with negative results divided by all normals.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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