Genetic variants in the CD59 gene: An exploratory study of large genome databases
Kshitij Srivastava1, Thomas Christopher Recupero1, Willy Albert Flegel1
1Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Insights
Researchers identified 160 CD59 gene variants, classifying them as neutral or deleterious. This analysis helps identify individuals at risk for CD59 deficiency symptoms, guiding personalized medical care.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- CD59 is a cell surface glycoprotein that prevents complement-mediated cell lysis.
- Deficiency in CD59 function is linked to recurrent strokes, neuropathy, and chronic hemolysis.
Purpose of the Study:
- To comprehensively analyze CD59 gene variants using public databases.
- To evaluate the potential pathophysiologic impact of identified CD59 variants.
Main Methods:
- Systematic compilation of CD59 variants from exons 4, 5, and 6 and splice sites across multiple populations and databases.
- Utilized the PredictSNP algorithm to assess the functional impact of non-synonymous variants.
Main Results:
- Identified 160 distinct CD59 alleles in 6881 subjects (0.7% of 488,592 individuals).
- Of 93 non-synonymous variants, 43 were predicted as deleterious and 49 as neutral.
- Among 14 non-synonymous variants in patients, 9 were deleterious (64.3%) and 5 were neutral (35.7%).
Conclusions:
- A comprehensive list of CD59 variants, classified by PredictSNP, was compiled from genomic databases.
- Findings can aid in identifying individuals with potential latent CD59 deficiency, such as those prone to hemolytic transfusion reactions.
- CD59 variant data, combined with clinical information, can support personalized treatment strategies.
Background:
CD59 is a GPI-anchored glycoprotein on the surface of many cell types. It inhibits the assembly of the membrane attack complex, thus preventing complement-mediated cell lysis. Lack of a functional CD59 protein causes recurrent ischemic strokes, neuropathy, and chronic hemolysis. We aimed at a comprehensive analysis of the CD59 gene from publicly available databases to identify variants and evaluate their pathophysiologic potential.
Methods:
Variants in the CD59 coding sequence of exons 4, 5, and 6 and their splice sites were systematically compiled from 4 major populations across 6 whole-genome and whole-exome databases. The PredictSNP algorithm assessed the functional impact of non-synonymous variants.
Results:
Among 488,592 individuals, 160 distinct alleles were identified in 6881 subjects (0.7%). Among 93 alleles with non-synonymous variants, 43 were classified as deleterious and 49 (2 variants encoded the same amino acid change) as neutral by PredictSNP. Additional variants included: 53 synonymous, 9 deletions/duplications, 3 splice site, and 2 nonsense. Among the 14 non-synonymous variants reported in patient samples, 9 were classified as deleterious (64.3%) and 5 as neutral (35.7%).
Discussion:
We collated a list of CD59 variants, which were classified as neutral or deleterious by PredictSNP, from genome databases. These results can be applied to identify individuals with possible latent CD59 deficiency symptoms, such as hemolytic transfusion reactions. In conjunction with clinical data, these CD59 variants can guide personalized clinical decisions.
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