Newborn screening and the era of medical genomics

Abstract

Across the span of the last 75+ years, technological and conceptual advances in genetics have found rapid implementation at the beginning of human life. From karyotype testing, to molecular cytogenetics, to gene panel testing, and now to whole exome and whole genome sequencing, each iterative expansion of our capability to acquire genetic data on the next generation has been implemented quickly in the clinical setting. In tandem, our continuously expanding ability to acquire large volumes of genetic data has generated its own challenges in terms of interpretation, clinical utility of the information, and concerns over privacy and discrimination; for the first time, we are faced with the possibility of having complete access to our genetic data from birth, if not shortly after conception. Here, we discuss the evolution of the field toward this new reality and we consider the potentially far-reaching consequences and, at present, an unclear path toward developing best practices for implementation.

Keywords: genetic testing; in vivo model organisms; newborn screening; next-generation sequencing; rare genetic disorders; whole exome/genome sequencing.

Figure 1. Next-generation sequence workflow complemented with functional studies

Upon consent of family members, collection of either blood or tissue is performed, followed by extraction of DNA. DNA is then fragmented and a sequence library is subjected to massively parallel sequencing. Resulting reads are processed and curated human genetic database to identify candidate variants that are/are not associated with human genetics diseases. The identification of genes or alleles not previously implicated in human genetic disease requires functional assays to test variants pathogenicity.