Genomic sequencing technologies for rare disease in mainstream healthcare: the current state of implementation

Genomic sequencing technologies, which include both exome and genome sequencing, as well as panels or targeted analyses using genome-wide approaches, are being implemented across healthcare. Implementation, however, varies greatly by application and jurisdiction, with a diversity of approaches being employed around the world. This review aims to summarise the current state of implementation of genomic testing in mainstream healthcare for the detection of rare disease throughout the lifespan. Through a discussion of evidence gathered to date, highlighting exemplar studies, the following applications of genomic testing will be covered: (1) routine diagnostic genomic testing in the clinic; (2) rapid diagnostic genomic testing in the intensive care unit; (3) genomic newborn screening; and, (4) reproductive genetic carrier screening. Mainstream implementation necessarily extends beyond the clinical genetics service, where genomic testing has historically been offered. Given that the involvement of non-genetics clinicians in the delivery of these technologies has important implications for models of care and education, related areas of growing evidence are also discussed: (5) genetic counsellors working outside clinical genetics services; and, (6) workforce development considerations for mainstream genomics. The diversity of approaches and examples illustrates that integration of genomic technologies into mainstream healthcare is complex and requires significant health system transformation. Efforts to evaluate services, guided by implementation science, will be essential to ensure lessons are shared across jurisdictions and benefit is delivered to patients and the system at-large.