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

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. 