Spontaneous recessive lethal mutations in the mouse

Abstract

The estimation of the load of recessive lethals in our inbred CBA strain is based on samples drawn from 1964 to 1971. 407 control F 1 males were back-crossed to their daughters. The first examined females which for each F 1 male gave 50 implants were included in the test. Their rate of intra-uterine death was compared to that from lethal-free males. The distribution of the number of F 1 males according to the number of dead in the first 50 implants were compared to a model of Lüning . Three estimates of the proportion of lethal heterozygotes gave 4.2, 5.35 and 6.2% respectively. From the way the inbred strain was kept it was estimated that the mean load among F 1 males was 11.5 μ ( μ = mutation rate per gamete). These data indicate that about 0.5% lethals occur per gamete with an upper limit of 1%. Comparisons are made with previous estimates of the spontaneous rate of lethal mutations per gamete. The low proportion of lethal mutations indicate that the number of loci giving lethal mutations is low. Both spontaneous and induced mutations give similar low numbers, more than one order of magnitude below the number commonly assumed. The uncertainties are stressed of estimating risk by multiplying mutation rate per locus and assumed number of loci.