Fig. 6

Fig. 6

a The Deciphering Developmental Disorders (DDD) study included 6139 non-coding regions in its sequence analysis of trios comprising affected individuals and unaffected parents^2,32. These non-coding regions were selected on the basis of high sequence conservation (ultra-conserved elements, UCEs, n = 4307), experimental validation (experimentally validated enhancers, EVEs, n = 595) or identification as a putative heart enhancer (PHE, n = 1237). Overlap with any H3K27ac, H3K4me3 or H3K27me3 1 kb bins is shown as an aggregate and for each individual category (UCE, EVE or PHE). b Equivalent overlap is shown for the 739 regions in which disease-associated de novo mutations (DNMs) were identified. c In total, 46% of DNM-positive regions were situated (+/− 1 kb) in at least one tissue-replicated H3K27ac and/or H3K4me3 bin. Over half of the disease-associated overlap was covered by the heart/LV (35%) and brain (18%). 75% of the disease-associated PHE regions were situated within 1 kb of a heart/LV-specific histone mark. d Enrichment in the number of DNMs overlapping (+/− 1 kb) H3K27ac marks during human organogenesis for individuals with neurodevelopmental (n = 671 cases), cardiac (n = 124 cases), limb (n = 312 cases) and eye (n = 288 cases) phenotypes. The circles represent the observed/expected ratio with asymmetrical error bars showing the 95% confidence limits calculated for a Poisson distribution (http://ms.mcmaster.ca/peter/s743/poissonalpha.html). For the neurodevelopmental phenotypes, this included analysis against DNAse hypersensitivity data and H3K27ac data from second trimester fetal brain¹⁰.