Monomeric and Multifactorial Parts

The family-linked British Columbia files have in addition yielded sib risk data for such conditions as strabismus, clefts of the palate and lip, clubfoot, heart malformations, spina bifida, and epilepsy of children. 27) It would thus be technically feasible to compare systematically for a wide range of diseases the actual risks among siblings of affected people with those expected for multifactorial quasicontinuous inheritance. 

The need for this kind of information becomes apparent when attempts are made to determine the combined frequency of the regularly inherited dominant diseases, which are of special interest as the only group of conditions likely to increase in direct proportion to an increase in the mutation rate. On the basis of a list of such diseases prepared for the United Nations Scientific Committee on the Effects of Atomic Radiation (see pp. 197-200), their combined frequency has sometimes been taken as affecting seriously approximately 1 % of liveborn individuals at some time in their lives. However, at the time when this list was prepared dominant inheritance of disease with single-gene causation was regarded as more common than it is now believed to be. The true figure may thus be substantially lower than the 1 %, perhaps by as much as tenfold. 

Current data are unfortunately inadequate to resolve the uncertainty. The point may be illustrated with the condition hydrocephalus, which is included in the list of dominants and accounts for one-fifth of the total cases in this category. From the British Columbia data, the risk to a sibling of an affected person is less than 2 %, so it clearly cannot be inherited as a simple dominant (or even as a simple recessive) in any substantial proportion of cases. In fact, similar uncertainty exists for many of the more common conditions that make up the bulk of the list (Table 1). 

The difficulties of compiling such a list of dominant diseases which includes their frequencies in a birth cohort become particularly apparent when attempts are made to derive appropriate data from the literature. For diseases that are sometimes inherited in a simple dominant 

TABLE 1. List of Autosomal Dominant Traits, in Descending Order of Frequency, Based on the Population of Northern Ireland  

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