Transmission of the Pi^Z allele for α₁-antitrypsin deficiency: population genetic considerations

Abstract

It is shown that a simple preferential transmission of the Pi^Z allele by Pi^Z-heterozygous males for 1-antitrypsin deficiency cannot maintain the observed polymorphism at the locus without invoking any viability or fertility selection against the Pi^Z gene carriers (heterozygotes or homozygotes). From the data on frequencies of Pi^Z alleles in Europe, the estimates of such selection coefficients are shown to be of the order of 5-20%, which seems too large for natural populations. Furthermore, an analysis of 26 nuclear families, each ascertained through a heterozygous Pi^Z or homozygous ZZ child, does not provide statistical evidence for such a hypothesis.