Extended Data Figure 3 : Genomic factors that affect mutation rate in non-coding elements.

From: De novo mutations in regulatory elements in neurodevelopmental disorders

Extended Data Figure 3

a, Aggregating CpG sites genome-wide into bins of methylation proportion from 0% (unmethylated in all cells) to 100% (methylated in all cells) and calculating the observed/expected ratio reveals differences in mutability not accounted for a by a triplet model alone. b, A mutation rate model incorporating a correction for CpG methylation explains greater variance in rare variant counts in the DDD unaffected parents. c, Levels of rare variation in deep whole genomes (n = 7,509 non-Finnish Europeans) were used to estimate power to detect a hypermutability of 1.1×, 1.2×, or 1.3×. d, The level of rare variation in the fetal brain-active elements (n = 2,613, FB(+)) is slightly lower than in the fetal brain-inactive elements (n = 1694, FB(-)), consistent with similar mutability between the two element sets with slightly stronger purifying selection in the fetal brain-active elements. e, f, Elements with DNMs observed in our study are not enriched in late-replicating regions (e) or in regions with higher recombination rate (f), which have been shown to be hypermutable.