Properties and rates of germline mutations in humans

• We describe insights into mutation rate from high-throughput genome sequencing of families.
• A paternal bias and agebeffect in mutation has been quantified at the genome-wide level.
• Copy number variants arise less frequently than do point mutations, but affect more bases.
• Future research will yield insights into the mutation rate of other forms of variation.

All genetic variation arises via new mutations; therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. However, advances in sequencing technology have allowed for empirical assessments of genome-wide rates of mutation. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age. Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). Here, we review the genome-wide analyses for the mutation rate of several types of variants and suggest areas for future research.