A method for analysing fertility of heterozygotes for autosomal recessive disorders, with special reference to cystic fibrosis, Tay-Sachs disease and phenylketonuria

Abstract

Increased fertility of heterozygotes with respect to decreased foetal loss among offspring of heterozygotes has been proposed by several authors as a possible explanation for the high gene frequency of CF, TSD and PKU in certain populations. Studies comparing reproductive outcome of heterozygotes with reproductive performance in the general population or in special control groups have been done on several occasions. These studies, however, are known to be heavily biased, on the one side by the fact that ascertainment of heterozygotes through affected offspinrg will tend to underestimate the relative frequency of smaller families, and on the other side because of the inadequacy of census data for comparison and the biases inherent in selection of control families. Careful analysis of the biases involved provides suggestions for proper corrections. From this a method has been developed which offers a better approach to the study of heterozygote fertility in those autosomal recessive conditions which lack a test for direct heterozygote detection.