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Updated: Apr 17, 2026
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
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On human disease-causing amino acid variants: statistical study of sequence and structural patterns.
Marharyta Petukh1, Tugba G Kucukkal1, Emil Alexov1
1Department of Physics, Clemson University, Clemson, SC 29642, USA.
Human Mutation
|February 18, 2015
Summary
Amino acid substitutions linked to diseases often cause significant changes in protein properties. These disease-associated mutations tend to destabilize protein structure and interactions, impacting overall function.
Area of Science:
- Biochemistry
- Genetics
- Structural Biology
Background:
- Human amino acid variations are common.
- Some variations are associated with diseases.
- Understanding these variations is crucial for disease research.
Purpose of the Study:
- To analyze the impact of amino acid substitutions on protein properties.
- To correlate these changes with disease association.
- To investigate the thermodynamic stability of mutated proteins.
Main Methods:
- Statistical analysis of human amino acid variations.
- Sequence and structural analysis of disease-associated variants.
- Analysis of experimental and computational thermodynamics data.
Main Results:
- Disease-causing amino acid substitutions often involve drastic changes in physicochemical properties (charge, hydrophobicity, geometry).
- These mutations significantly alter protein structural features like hydrogen bonds and salt bridges.
- Amino acid mutations, in general, tend to destabilize proteins and their interactions.
Conclusions:
- Significant alterations in protein physicochemical properties, structure, and thermodynamics are linked to disease.
- Protein destabilization by amino acid mutations is a general phenomenon.
- Changes in protein properties can predict disease association.
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