Lessons learned from the search for genes responsible for rare Mendelian disorders.

Abstract

The last decade has witnessed dramatic improvements in DNA sequencing technology with reduced cost, increased throughput, and improved analytic tools and resources. A consequence of this technologic revolution is the rapid emergence of approaches applying these next‐generation sequencing (NGS) methods to many areas of medicine including discovery research and clinical diagnosis. Some consequences of this revolution include the ability to make molecular diagnosis for thousands of inherited phenotypes; molecular characterization of cancers that enable diagnostic refinement and individualized therapy; elucidation of pharmacogenetic susceptibilities, and enumeration of individual architectures of genetic variation conferring risk for common complex traits such as coronary artery disease, diabetes, and neuropsychiatric disease. These newly acquired capabilities form the cornerstone for individualized or precision medicine of the future.