Study of Mutation at the Molecular Level

Changes in amino acid sequence of proteins (primary structure). Changes in protein function, measured directly by determining enzyme activity or antigenicity (secondary and tertiary structure).  

Alterations in the level of enzymes or enzyme products, i.e., metabolites. 

Morphological or behavioral changes (gross phenotypic changes). 

At present, the approach of preference appears to be the search for qualitative differences, such as the appearance of an enzyme band in an electropherogram where none was present before, rather than a quantitative difference in a substance which is always present. For normal blood or urine constituents, normal values vary over a considerable range, and the values seen in a subpopulation known to have a given genetic disease may overlap it. This is especially true for metabolites, where alternate biochemical pathways and compensatory changes due to either homeostatic mechanisms or therapy may exist. Hence our initial emphasis is on the detection of qualitative changes in substances which are direct gene products. 

The approach advocated in this presentation for initial use is conceptually and technically simple. Electrophoresis has been shown to be a pK)werful tool in detecting those amino acid substitutions in proteins which 

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