biostudies-literatureSung MKKAIST InstituteKAISTThe Ministry of Science, ICT and Future PlanningUlsan National Institute of Science and Technology164https://www.ebi.ac.uk/biostudies/studies/S-EPMC4964047biostudies-literatureUnknown17(1)<h4>Background</h4>Examples of heterozygote advantage in humans are scarce and limited to protein-coding sequences. Here, we attempt a genome-wide functional inference of advantageous heterozygosity at cis-regulatory regions.<h4>Results</h4>The single-nucleotide polymorphisms bearing the signatures of balancing selection are enriched in active cis-regulatory regions of immune cells and epithelial cells, the latter of which provide barrier function and innate immunity. Examples associated with ancient trans-specific balancing selection are also discovered. Allelic imbalance in chromatin accessibility and divergence in transcription factor motif sequences indicate that these balanced polymorphisms cause distinct regulatory variation. However, a majority of these variants show no association Genome biologySelected heterozygosity at cis-regulatory sequences increases the expression homogeneity of a cell population in humans.PMC4964047N111600691.1500872013M3A9C4078139Future Systems Healthcare ProjectLee KSChoi JKGhim CMSung MKJang JfalseSelected heterozygosity at cis-regulatory sequences increases the expression homogeneity of a cell population in humans.<h4>Background</h4>Examples of heterozygote advantage in humans are scarce and limited to protein-coding sequences. Here, we attempt a genome-wide functional inference of advantageous heterozygosity at cis-regulatory regions.<h4>Results</h4>The single-nucleotide polymorphisms bearing the signatures of balancing selection are enriched in active cis-regulatory regions of immune cells and epithelial cells, the latter of which provide barrier function and innate immunity. Examples associated with ancient trans-specific balancing selection are also discovered. Allelic imbalance in chromatin accessibility and divergence in transcription factor motif sequences indicate that these balanced polymorphisms cause distinct regulatory variation. However, a majority of these variants show no association 2016-01-01T00:00:00Z2016 Jul2026-06-17T06:02:59.879Z2026-06-17T03:07:52.773ZS-EPMC49640472746889710.1186/s13059-016-1027-8