Genetic testing of patient constitutional DNA (i.e., their genome) is increasingly performed in medical practice. Sequencing an entire human genome (about 3.2 billion nucleotides) is now possible to complete in days to weeks, and at a similar cost to some advanced imaging tests or to a brief admission to hospital. Genome sequencing is being integrated into health care systems internationally, most notably in the United Kingdom. Starting in 2021, genome sequencing is being performed as a clinical genetic test in Ontario, Canada. What is genome sequencing? Genome sequencing (or whole genome sequencing) is a comprehensive test capable of detecting nearly all DNA variation in a genome. Sequencing can diagnose most of the > 6000 conditions listed in the Online Mendelian Inheritance in Man database (www.omim.org) for which the genetic basis is currently understood. These include cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolemia, hemophilia A, Lynch syndrome, Marfan syndrome and multiple endocrine neoplasia. Most diagnoses are individually rare (i.e., < 1 in 2000 live births) or ultra-rare (i.e., < 100 people reported in the medical literature), and thus less likely to be suspected a priori (e.g., Kabuki syndrome; Figure 1). Patients may present with unusual constellations of features, or with common diseases like autism spectrum disorder, cardiomyopathy, congenital heart disease, epilepsy, cancer, schizophrenia or dementia, although this list is not comprehensive.
Gregory Costain、Ronald D. Cohn、Stephen W. Scherer、Christian R. Marshall
NSTL
