An experimental method for evaluating the contribution of deleterious mutations to quantitative trait variation

Abstract

Unconditionally deleterious mutations could be an important source of variation in quantitative traits. Deleterious mutations should be rare (segregating at low frequency in the population) and at least partially recessive. In this paper, I suggest that the contribution of rare, partially recessive alleles to quantitative trait variation can be assessed by comparing the relative magnitudes of two genetic variance components: the covariance of additive and homozygous dominance effects (C(ad)) and the additive genetic variance (V(a)). If genetic variation is due to rare recessives, then the ratio of C(ad) to V(a) should be equal to or greater than 1. In contrast, C(ad)/V(a) should be close to zero or even negative if variation is caused by alleles at intermediate frequencies. The ratio of C(ad) to V(a) can be estimated from phenotypic comparisons between inbred and outbred relatives, but such estimates are likely to be highly imprecise. Selection experiments provide an alternative estimator for C(ad)V(a), one with favourable statistical properties. When combined with other biometrical analyses, the ratio test can provide an incisive test of the deleterious mutation model.