Prevalence of whole-genome sequencing and high-quality annotations of the human genome has started to allow exploration of some of the mechanisms of gene regulation on an organismal scale in humans. Until recently, most efforts have focused on examining the effect of variation in protein coding regions on human phenotype. However, with the release of many whole-genome regulatory annotations, both biochemical and genetic, it has started to become possible to assign putative regulatory function to non-coding DNA. This is particularly significant as a majority of human variation associated with disease falls outside of gene bodies. As a resource, RegulomeDB has provided a concise method to assign putative function to variation. The research project aspects of this proposal will expand and support RegulomeDB. We have demonstrated that RegulomeDB has provided a valuable resource to the community. Here we will detail the efforts required to expand the utility of RegulomeDB to take advantage of the vast array of data generated by labs performing high-throughput ?omics research.
TO PUBLIC HEALTH, PROJECT NARRATIVE The regulation of gene expression controls the determination of cell types, and aberrant gene expression can cause diseases such as cancer. RegulomeDB will enable researchers, clinicians, and sophisticated computer programs to relate DNA variants that lie in previously poorly understood regions of the human genome to possible functions thereby helping us understand the genetic basis of human variation and disease.
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| Nishizaki, Sierra S; Boyle, Alan P (2017) Mining the Unknown: Assigning Function to Noncoding Single Nucleotide Polymorphisms. Trends Genet 33:34-45 |
| Yang, Bo; Zhou, Wei; Jiao, Jiao et al. (2017) Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nat Commun 8:15481 |
