Tests for a Mutation-Maintained Component

For the purpose of pedigree studies to identify sporadic cases of dominant diseases, the routine records in their linked form would provide information on family composition for whole populations and would serve as an aid in finding the cases. While the extent of the labor saved would be considerable, it is probable that substantial further work of conventional kinds would be needed where the coded diagnoses lacked the required specificity. This would be true also where it was decided to extend the family histories to include events of ill health not represented in the routine records for the region, e.g., because of the movements of people into and out of the area under study. 

Experience has been gained with such studies using the British Columbia records. An effect of advancing maternal age has in this manner been demonstrated for mongolism, cerebral palsy, and congenital malfor- 

There appear to be only two ways of avoiding or minimizing biases of this sort. One is to restrict such studies to those hereditary diseases which are uninfluenced in their expression by environmental factors, and the other is to control for all social variables which may be correlated with environmental differences that affect the expression of the diseases. With either approach, very substantial populations must be investigated. In the first approach, this is because only a few rare dominant diseases qualify for study. In the second, where the tabulations must be broken down into subsets homogeneous for a multiplicity of social variables, large quantities of data are needed to permit comparisons within subsets. 

Thus if indications of an important mutational component in human genetic disease are to be obtained from studies of sporadic cases or from correlations of risks with parental (or grandparental) ages, data from 

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