Boycott · Nature reviews. Genetics 2013 · narrative review · n=?

Rare-disease genetics in the era of next-generation sequencing: discovery to translation.

Cited 769 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review without systematic methodology or primary human data.

PubMed 23999272 · doi:10.1038/nrg3555 · record verified 2026-08-26

What was done

This narrative review synthesized the evolution of rare-disease genetics enabled by next-generation sequencing. The authors examined strategies for identifying disease-causing genes and evaluated their clinical and translational impacts across diagnostics, mechanistic understanding, and therapeutic development.

What was found

The authors report that over the preceding 25 years, causal genes were identified for approximately 50% of an estimated 7,000 rare monogenic diseases. They noted projections that most remaining disease-causing genes would be discovered by 2020 due to advances in DNA-sequencing technologies and computational analyses. No primary experimental numbers or statistical analyses were reported in the abstract.

Why it matters

The paper outlines the transition of rare-disease genetics from basic gene discovery to clinical diagnostic integration and targeted therapeutic development.

Limits

As a narrative review, it lacks a systematic search protocol, study quality assessment, or primary empirical data. Projections regarding gene discovery timelines represent expert estimates rather than prospectively tested empirical endpoints.

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