Gene and Variant Annotation for Mendelian Disorders in the Era of Advanced Sequencing Technologies

Abstract

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. 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. This ultimately will facilitate better patient recruitment in clinical trials. 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. 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. We also discuss the utility of this integrated approach for diagnostic clinics and medical databases and its role in the future of personalized medicine.

Keywords: MPS; Mendelian disorders; NGS; clinical genomics; exome; gene annotation; genome; massively parallel sequencing; next-generation sequencing; targeted gene panel; variant.