Whole-genome and whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. The term newborn screening refers to public health programs designed to screen newborns for various treatable metabolic conditions, by measuring levels of circulating blood metabolites. The availability and significant decrease in sequencing costs has raised the question of wh...

It is not economically feasible to sequence all study subjects in a large cohort. A cost-effective strategy is to sequence only the subjects with the extreme values of a quantitative trait. In the National Heart, Lung, and Blood Institute Exome Sequencing Project, subjects with the highest or lowest values of body mass index, LDL, or blood pressure were selected for whole-exome sequencing. Fail...