Determining de novo mutation rates

Abstract

Knowing the human de novo mutation rate is important for understanding our evolution and the origins of genetic diseases. These two papers characterize the de novo mutation rate, both using Icelandic families. Kong et al. sequenced the whole genomes of 78 parent–offspring trios at high coverage to study the mutation rate directly, whereas Sun et al. analysed more than 85,000 individuals at 2,477 microsatellite repeats to get an indirect measurement. Both studies found that the paternal contribution to the de novo mutation rate is higher than that of the mother and that maternal age is not an important determinant. However, the rates estimated in the two studies are different (1.2 × 10−8 and 1.4 to 2.3 × 10−8 mutations per nucleotide per generation for Kong et al. and Sun et al., respectively), and Kong et al. identified a much stronger effect of paternal age; these discrepancies require further study.