Genetic analysis of human complement factor H polymorphisms.
Rie Susukida1, Akira Kido, Masakazu Oya
1Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato, Yamanashi, Japan.
Electrophoresis
|December 21, 2006
Summary
Human complement factor H (factor H) phenotypes are not caused by factor H gene variations. Instead, HF phenotypes likely result from genetic changes in factor H-related protein 1, suggesting new research directions.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Human complement factor H (factor H) exhibits polymorphism with known FH and HF alleles.
- The genetic basis for factor H phenotypes and the relationship between FH and HF alleles remain unclear.
Purpose of the Study:
- To investigate the genetic and protein basis of human complement factor H (factor H) phenotypes.
- To determine if observed HF phenotypes correlate with variations in the factor H gene or protein.
Main Methods:
- Nucleotide sequence analysis of complementary DNA (cDNA) from individuals with different HF phenotypes.
- Western blotting and 2-dimensional electrophoresis (2-DE) to analyze factor H protein expression.
- Development of a novel PCR-RFLP method to detect factor H gene polymorphisms.
Main Results:
- Nucleotide sequencing revealed seven mutated sites in the factor H gene, but some sequences were shared across different HF phenotypes.
- Western blotting and 2-DE showed factor H protein expression in all tested HF phenotypes, with specific cross-reacting polypeptides present in HF A, HF B, and HF AB, but not HF Q0.
- HF phenotypes did not show a strong correlation with structural variations in the factor H gene or protein.
Conclusions:
- Human complement factor H (factor H) phenotypes are unlikely to be caused by polymorphisms directly within the factor H gene.
- Evidence suggests that HF phenotypes may be associated with polymorphism in the factor H-related protein 1 gene.
- A new PCR-RFLP method for detecting factor H gene polymorphisms could aid in genetic disease studies.
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