Genome-Wide Analysis of Human Disease Alleles Reveals That Their Locations Are Correlated in Paralogous Proteins
Author Information
Author(s): Yandell Mark, Moore Barry, Salas Fidel, Mungall Chris, MacBride Andrew, White Charles, Reese Martin G.
Primary Institution: Eccles Institute of Human Genetics, University of Utah
Hypothesis
Can the locations of variants in paralogous proteins help identify disease-causing variants?
Conclusion
The study found that variant locations are correlated in paralogous proteins, suggesting that information about these variants can help identify potentially disease-causing mutations.
Supporting Evidence
- Variants co-occur at aligned amino acid pairs more frequently than expected by chance.
- If one member of a variant-pair is disease-causing, its partner is likely to be disease-causing as well.
- More than 25% of the OMIM alleles are nonsense mutations.
- Known disease-causing alleles tend to preferentially align with one another.
Takeaway
Scientists looked at how changes in genes that are similar to each other can help find mutations that cause diseases. They found that if one gene has a harmful change, its similar gene is likely to have one too.
Methodology
The study analyzed known disease-causing variants from databases and examined their distribution in paralogous proteins using computational methods.
Potential Biases
Potential biases may arise from the reliance on existing databases for variant information.
Limitations
The study primarily focused on known disease-causing variants and may not account for all possible mutations.
Statistical Information
P-Value
p<1e-4
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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