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Accurate annotation of variants in coding, noncoding, or intergenic regions is important to understand their functional effects, whether disease-causing pathogenic or random genetic drift. Knowledge of the complexities of genomic association has vastly increased compared with what was known only a decade ago ( Figures 1 and 2).Īccurate annotation of genes is critical to understand the locations of the coding and noncoding regions of the genes in the genome and their functional associations with pathways in normal and disease states. The understanding of genotype-phenotype and gene-disease associations has evolved as research has uncovered evidence of genetic pleiotropy and multigenic effects of disease (to name just a few examples).

Moreover, fundamental knowledge of how a single gene affects a single phenotype or disorder is no longer in its infancy. Basic science is more free to delve into newer concepts that clinical science typically approaches with extreme caution however, new technologies are beginning to blur the line between basic and clinical sciences. Traditionally, basic and clinical sciences have followed parallel paths, with the latter branching off from the former once a discovery is made. The increased ability to understand DNA and its downstream products has opened up new areas of investigation, especially in understanding the basic functional unit of DNA: the gene. The last decade has brought unprecedented technological advances in all areas of genomics.

We also discuss the utility of this integrated approach for diagnostic clinics and medical databases and its role in the future of personalized medicine. We describe the emerging field of translational functional genomics, which integrates other functional “-omics” approaches that support next-generation sequencing genomic data in order to facilitate personalized diagnostics, disease management, biomarker discovery, and medicine.

In this review, we describe the trends in research at the intersection of basic and clinical genomics that aims to increase understanding of overall genomic complexity, complex inheritance patterns of disease, and patient-phenotype-specific genomic associations. This ultimately will facilitate better patient recruitment in clinical trials. Progress in the development of faster and more accurate pipelines for genome annotation and variant classification will lead to the discovery of more novel disease associations and candidate therapeutic targets. Comprehensive annotations of genetic and noncoding regions and corresponding accurate variant classification for Mendelian diseases are the next big challenge in the new genomic era of personalized medicine.

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