BackgroundWe describe the distribution of indels in the 44 Encyclopedia of DNA Elements (ENCODE) regions (about 1% of the human genome) and evaluate the potential contributions of small insertion and deletion polymorphisms (indels) to human genetic variation. We relate indels to known genomic annotation features and measures of evolutionary constraint.ResultsIndel rates are observed to be reduced approximately 20-fold to 60-fold in exonic regions, 5-fold to 10-fold in sequence that exhibits high evolutionary constraint in mammals, and up to 2-fold in some classes of regulatory elements (for instance, formaldehyde assisted isolation of regulatory elements [FAIRE] and hypersensitive sites). In addition, some noncoding transcription and other chromatin mediated regulatory sites also have reduced indel rates. Overall indel rates for these data are estimated to be smaller than single nucleotide polymorphism (SNP) rates by a factor of approximately 2, with both rates measured as base pairs per 100 kilobases to facilitate comparison.ConclusionIndel rates exhibit a broadly similar distribution across genomic features compared with SNP density rates, with a reduction in rates in coding transcription and evolutionarily constrained sequence. However, unlike indels, SNP rates do not appear to be reduced in some noncoding functional sequences, such as pseudo-exons, and FAIRE and hypersensitive sites. We conclude that indel rates are greatly reduced in transcribed and evolutionarily constrained DNA, and discuss why indel (but not SNP) rates appear to be constrained at some regulatory sites.