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Updated: May 18, 2026
11:35
Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
Published on: August 21, 2016
Inferring causality and functional significance of human coding DNA variants
1Genetics Division, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ssunyaev@rics.bwh.harvard.edu
Human Molecular Genetics
|September 20, 2012
Summary
Identifying the functional impact of human genetic variations is crucial for understanding traits and diseases. This review explores statistical, experimental, and computational evidence to pinpoint significant DNA variants in protein-coding genes.
Area of Science:
- Genetics
- Genomics
- Bioinformatics
Background:
- Human genetic variation is extensively characterized by sequencing technologies.
- Statistical genetics links numerous genetic loci to medically relevant phenotypes.
- A key challenge remains identifying functionally significant alleles causally involved in human traits.
Purpose of the Study:
- To review evidence for the functional significance of human DNA variants within protein-coding genes.
- To highlight the integration of diverse data sources for variant interpretation.
Main Methods:
- Review of statistical genetics evidence (co-segregation, allele frequency, recurrence).
- Evaluation of in vitro functional assays and model organism studies.
- Assessment of computational prediction methods for amino acid substitutions.
Main Results:
- Multiple lines of evidence contribute to assessing variant functional significance.
- Statistical genetics provides population-level insights into variant impact.
- Functional assays and computational tools offer mechanistic and predictive data.
Conclusions:
- Characterizing the functional impact of human genetic variants is complex.
- Integrating statistical, experimental, and computational approaches is essential.
- Despite progress, challenges persist in fully elucidating variant roles in human traits.
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