The correction of disease-causing mutations in human embryos could reduce the burden of inherited genetic disorders in the fetus and newborn, and improve the efficiency of fertility treatments for couples with disease-causing mutations in lieu of embryo selection. Here we evaluate the repair outcomes of a Cas9-induced double-strand break (DSB) introduced on the paternal chromosome at the EYS locus, which carries a frame-shift mutation causing blindness.We show that the most common repair outcome is microhomology-mediated end joining, which occurs during the first cell cycle in the zygote, leading to embryos with non-mosaic restoration of the reading frame. However, about half of the breaks remain unrepaired, resulting in an undetectable paternal allele and, upon entry into mitosis, loss of one or both chromosomal arms.Thus, Cas9 allows for the modification of chromosomal content in human embryos in a targeted manner, which may be useful for the prevention of trisomies.

Using a panel of somatic cell hybrids, we have localised the 30-kDal Rhesus blood group-antigen-related protein to human chromosome 1 in the region p36.13→p34. This confirms the localisation of this protein described previously using cytogenetic and linkage analyses.

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Simple models of viability selection acting on variation at a single diploid locus only maintain multiple alleles for very restricted sets of fitnesses. Most of these models assume that fitnesses are independent, even if the genotypes share alleles. Here, we extend this result to a model with generalized dominance interactions, in which fitnesses are strongly affected by what we call the “primary effects” of the genotype’s component alleles, so that genotypes with shared alleles have correlated fitnesses. Nevertheless, in keeping with previously reported results, we also show that such fitness sets are easily constructed over time if recurrent mutation is occurring simultaneously. We find that such models maintain less variation over time than do (previous) models with independently sampled fitnesses, especially when the effects of genetic drift are taken into account. We also show that there is a weak tendency for greater weighting of primary effects to evolve over time.