DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification

Abstract

When is a mutation a true genetic variant? Large-scale sequencing studies have set out to determine the low-frequency pathogenic genetic variants in individuals and populations. However, Chen et al. demonstrate that many so-called low-frequency genetic variants in large public databases may be due to DNA damage. They scored libraries sequenced with and without a DNA damage–repairing enzymatic mix to assess the proportion of true rare variants. It remains to be seen how best to repair DNA before sequencing to provide more accurate assessments of mutation. Science , this issue p. 752