Realizing the significance of noncoding functionality in clinical genomics

Clinical genomics promises unprecedented precision in understanding the genetic basis of disease. Understanding the impact of variation across the genome is required to realize this potential. Currently, clinical genomics analyses focus on protein-coding genes. However, the noncoding genome is substantially larger than the protein-coding counterpart, and contains structural, regulatory, and transcribed information that needs to be incorporated into genome annotations if the full extent of the opportunity to use genomic information in healthcare is to be realized. This article reviews the challenges and opportunities in unlocking the clinical significance of coding and noncoding genomic information and translating its utility in practice. Most of the DNA in the genome does not consist of genes that code for proteins, and understanding the function of these less examined parts of our genetic material is essential to fully understand human development and disease. Brian Gloss and Marcel Dinger at the Garvan Institute of Medical Research in Sydney, Australia, review the challenges and opportunities in unraveling the clinical significance of all parts of our DNA. Many regions of DNA that do not encode protein molecules perform crucial functions in regulating the activity and interactions of the protein-coding genes. Variations in these regions may significantly influence the risks and causes of disease. Studying all parts of the genome will be critical for ensuring that the powerful modern techniques of genetic analysis have maximal impact on healthcare.