Pulse Brain · Growing Health Evidence Index
Tier 4 — Narrative / commentaryPeer-reviewed

From variant to function in human disease genetics

Tuuli Lappalainen, Daniel G. MacArthur

Science · 2021

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Summary

This review article examines the emerging challenge of translating genetic variant discovery into functional understanding of disease mechanisms. The authors discuss rationale, methods, and applications for characterising variant impact at scale using patient tissues and in vitro systems, with increasing clinical deployment. They argue that improved functional variant interpretation will substantially advance disease diagnosis, risk prediction, and therapeutic development.

UK applicability

The methodological frameworks and functional variant interpretation approaches discussed are broadly applicable to UK genomic medicine and clinical genetics practice. UK healthcare systems and research institutions increasingly use these methods in clinical settings, particularly within NHS genomic medicine services.

Key measures

Functional variant interpretation methods; molecular and cellular effects of genetic variants; disease risk prediction; diagnostic accuracy

Outcomes reported

The paper reviews methods for characterising how genetic variants influence phenotypes and disease risk through molecular and cellular effects. It synthesises approaches using patient tissue samples and in vitro models to dissect variant mechanisms across human cell types.

Theme
Measurement & metrics
Subject
Measurement methods & nutrient profiling
Study type
Narrative Review
Study design
Narrative review
Source type
Peer-reviewed study
Status
Published
System type
Laboratory / in vitro
DOI
10.1126/science.abi8207
Catalogue ID
SNmoj44b9n-zp5pg2

Topic tags

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