Related Experiment Videos
Decay-accelerating factor. Genetic polymorphism and linkage to the RCA (regulator of complement activation) gene
Insights
The human decay-accelerating factor (DAF) gene is located within the regulator of complement activation (RCA) gene cluster. This finding clarifies the genetic organization of key complement regulatory proteins.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- The human decay-accelerating factor (DAF) is structurally and functionally related to complement components like CR1, C4bp, and factor H.
- These complement components are encoded by genes within the regulator of complement activation (RCA) gene cluster.
Purpose of the Study:
- To investigate the genetic relationships between the human DAF and complement components CR1, C4bp, and factor H.
- To determine the precise location of the DAF gene within the RCA gene cluster.
Main Methods:
- Southern blot analysis of genomic DNA using a DAF cDNA probe.
- Restriction fragment length polymorphism (RFLP) analysis with Bam HI and Hind III.
- Segregation analysis of polymorphic fragments in informative families.
Main Results:
- DAF exhibits restriction fragment length polymorphism, indicating its genetic variability.
- Segregation analysis confirmed that the DAF gene resides within the RCA gene cluster.
- No recombinants were observed between DAF and C4BP/CR1 in 32 informative meioses.
- DAF segregated with the CR1/C4BP segment in individuals with recombination between CR1/C4BP and H, indicating DAF is closer to CR1/C4BP than to H.
Conclusions:
- The gene encoding human DAF is located within the regulator of complement activation (RCA) gene cluster.
- The DAF gene maps proximally to the C4-binding protein (C4BP) and C3b/C4b receptor (CR1) genes.
- Genetic recombination can separate the DAF gene from the factor H gene within the RCA cluster.
Abstract:
We have investigated the genetic relationships between the human decay-accelerating factor (DAF) and a group of complement components including the C3b/C4b receptor (CR1), C4-binding protein (C4bp), and factor H (H), to which DAF is structurally and functionally related. CR1, C4bp, and H were previously demonstrated to be encoded by a cluster of closely linked genes, which we have designated regulator of complement activation (RCA). Southern blot analysis of genomic DNA using a DAF cDNA probe unraveled the existence of restriction fragment length polymorphism (RFLP) for both Bam HI and Hind III restriction endonucleases. Segregation analysis of these polymorphic fragments in families informative for the segregation of alleles at the CR1, C4BP, and H loci (RCA-haplotypes), demonstrated that, in humans, the gene encoding DAF is located within the RCA gene cluster. No recombinants between DAF and C4BP/CR1 were encountered in 32 informative meioses. In addition, in two individuals showing recombination between the CR1/C4BP and H loci, DAF segregated with the CR1/C4BP segment. Thus, the DAF gene maps closer to the CR1/C4BP loci than to the H gene, from which it can be separated by genetic recombination.