Evaluating single nucleotide polymorphisms in beta - 2 - microglobulin - a theoretical study
Ammar K Daoud1, Wafa' A Alqarqaz2, Majduleen M Al Okor1
1Department of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Frontiers in Immunology
|September 18, 2025
Summary
Single Nucleotide Polymorphisms (SNPs) can alter Beta 2 Microglobulin (B2M) protein structure. Our analysis reveals that most SNPs cause significant amino acid substitutions, potentially impacting protein function and highlighting the need for improved computational tools.
Area of Science:
- Immunology
- Computational Biology
- Genetics
Background:
- Beta 2 Microglobulin (B2M) is a conserved single-domain protein within the Immunoglobulin Superfamily.
- B2M exhibits a low rate of Single Nucleotide Polymorphisms (SNPs) across vertebrates.
Purpose of the Study:
- To mathematically evaluate the impact of SNP-induced amino acid (AA) substitutions on the primary structure of B2M.
- To assess the significance of these AA substitutions using established scoring systems.
Main Methods:
- Developed a C++ program to analyze 360 B2M DNA sequences and predict corresponding 119 AA protein sequences.
- Generated all possible 3 SNPs per nucleotide and assessed 9 modifications per triplet.
- Utilized Sneath Score to evaluate the chemical resemblance of AA substitutions.
Main Results:
- 22.1% of SNPs resulted in no AA change; 25.4% caused minor changes within AA groups.
- 5.3% of SNPs generated stop codons, leading to premature transcription termination.
- 47.2% of SNPs resulted in significant AA substitutions across different chemical groups.
Conclusions:
- SNPs in B2M are random events that can alter protein structure.
- A significant proportion of SNPs lead to substantial AA changes, potentially affecting protein function.
- There is a need for enhanced computational tools and scoring systems to accurately evaluate SNP effects on protein structure.
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