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Polymorphism and deficiency of human factor H-related proteins p39 and p37
E Feifel1, W M Prodinger, M Mölgg
1Institut für Hygiene, Leopold-Franzens University, Innsbruck, Austria.
Abstract:
We described previously cDNA clones representing a novel factor H-related 1.4 kilobase mRNA. This mRNA species codes for a doublet of serum proteins of M(r) 39,000 and 37,000 (p39/p37). The respective recombinant proteins of the three clones H-69, pFH1.4a, and pFH1.4b differ in the expression of the epitope recognized by the monoclonal antibody (mAb) 3D11. This probably reflects the difference of three amino acid residues of the deduced protein sequence. Here we report evidence for corresponding alterations in the native proteins p39/p37 in human sera. Employing mAb 3D11 and a polyclonal factor H-specific antiserum we detected three different patterns in western blot analyses of human sera which we provisionally termed FH1.4p+m+, FH1.4p+m-, and FH1.4p-m-. In the first pattern, p39/p37 were recognized by both antibodies, while in the second pattern the two proteins reacted only with the polyclonal antiserum. Both antibodies failed to detect p39/p37 in the third pattern. These phenotypes are found in the healthy population with frequencies of 0.556, 0.40, and 0.044, respectively. The frequencies of the alleles FH1.4*p+m+, FH1.4*p+m-, and FH1.4*p-m- were estimated to be 0.33, 0.46, and 0.21, respectively, assuming the gene distribution to be in Hardy-Weinberg equilibrium. Studies of 98 members from 27 families revealed an autosomal Mendelian inheritance. Southern blot data support our assumption of a polymorphism of the factor H-related proteins p39 and p37.
Insights
This study identifies genetic variations in factor H-related proteins (p39/p37) in human serum, revealing a common polymorphism with three distinct patterns. These variations follow autosomal Mendelian inheritance, impacting protein recognition by specific antibodies.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- A novel factor H-related 1.4 kilobase mRNA codes for serum proteins p39/p37.
- Recombinant proteins from cDNA clones show variations in epitope expression recognized by monoclonal antibody (mAb) 3D11.
- These variations likely stem from differences in amino acid sequences.
Purpose of the Study:
- To investigate corresponding alterations in native p39/p37 proteins in human sera.
- To characterize the polymorphism of factor H-related proteins p39 and p37.
- To determine the inheritance pattern of these protein variations.
Main Methods:
- Western blot analysis of human sera using mAb 3D11 and a polyclonal factor H-specific antiserum.
- Detection of three distinct protein patterns (FH1.4p+m+, FH1.4p+m-, FH1.4p-m-).
- Family studies involving 98 individuals from 27 families and Southern blot analysis.
Main Results:
- Three phenotypes were identified in the healthy population with frequencies of 0.556, 0.40, and 0.044.
- Allele frequencies were estimated as FH1.4*p+m+ (0.33), FH1.4*p+m- (0.46), and FH1.4*p-m- (0.21) under Hardy-Weinberg equilibrium.
- Autosomal Mendelian inheritance was confirmed through family studies, supporting a polymorphism in factor H-related proteins.
Conclusions:
- A common polymorphism exists for factor H-related proteins p39 and p37 in human populations.
- This polymorphism affects the recognition of these proteins by specific antibodies.
- The inheritance pattern is autosomal Mendelian, providing insights into complement system regulation.