Living laboratory: whole-genome sequencing as a learning healthcare enterprise.

Journal Article (Review;Journal Article)

With the proliferation of affordable large-scale human genomic data come profound and vexing questions about management of such data and their clinical uncertainty. These issues challenge the view that genomic research on human beings can (or should) be fully segregated from clinical genomics, either conceptually or practically. Here, we argue that the sharp distinction between clinical care and research is especially problematic in the context of large-scale genomic sequencing of people with suspected genetic conditions. Core goals of both enterprises (e.g. understanding genotype-phenotype relationships; generating an evidence base for genomic medicine) are more likely to be realized at a population scale if both those ordering and those undergoing sequencing for diagnostic reasons are routinely and longitudinally studied. Rather than relying on expensive and lengthy randomized clinical trials and meta-analyses, we propose leveraging nascent clinical-research hybrid frameworks into a broader, more permanent instantiation of exploratory medical sequencing. Such an investment could enlighten stakeholders about the real-life challenges posed by whole-genome sequencing, such as establishing the clinical actionability of genetic variants, returning 'off-target' results to families, developing effective service delivery models and monitoring long-term outcomes.

Full Text

Duke Authors

Cited Authors

  • Angrist, M; Jamal, L

Published Date

  • April 2015

Published In

Volume / Issue

  • 87 / 4

Start / End Page

  • 311 - 318

PubMed ID

  • 25045831

Pubmed Central ID

  • PMC4302048

Electronic International Standard Serial Number (EISSN)

  • 1399-0004

International Standard Serial Number (ISSN)

  • 0009-9163

Digital Object Identifier (DOI)

  • 10.1111/cge.12461


  • eng