Between hype and hope: whole-genome sequencing in clinical medicine

摘要: The promise of genomic & personalized medicine Ultra-high-throughput sequencing (UHTS) has profoundly impacted medical research because its ability to accelerate the pace targeted resequencing subsets [1,2]. Many genes can now be investigated simultaneously, and entire genomes (including tumor genomes) [3,4] sequenced rapidly efficiently. UHTS detected mutations associated with inherited acquired genetic diseases, explored microbial diversity, transcriptome, characterized DNA-binding proteins analyzed chromatin [5]. cost is dropping so fast that we envision affordable comprehensive genotyping-guiding care, as well lifestyle reproductive decisions. Medical applications reduce morbidity mortality, optimize quality life, by enabling more proactive healthcare – basically, adding genomeguided ‘predict prevent’ approaches existing ‘diagnose treat’ model clinical [6]. In diagnostic applications, will probably become a ‘disruptive’ technology; not simply spectrum molecular tools but rather replacing traditional [7]. Indeed, forms ‘whole-genome ana lysis’ already are available commercial direct-to-consumer testing; DNA samples being submitted for purposes ranging from recreational (e.g., “Am I related Genghis Khan?”) medical, including exploration traits, disease associations, paternity ancestry [7,8]. Genome analyses, however, soon enter sphere physiciandirected well, this affect patients providers, pharmaceutical companies, payers, regulators policy-makers. Clinical laboratories adopt technology short full genome sequencing, yet transform their current capabilities. For example, enables pharmacogenetic correlations (to support individually tailored treatment) conditions exons, introns promoter regions one or hundreds simultaneously. also permit evaluation aneuploidy other structural variations, detection epigenetic events correlated diseases complex traits. Cancers could potentially prevented, early, fully characterized, monitored optimally treated. Infectious testing revolutionized introduction metagenomics patient diagnosis [9]. When becomes reality, experience paradigm shift.