Structure and organization of the C4 genes

Area of Science:

• Human genetics
• Immunogenetics
• Molecular biology

Background:

• The complement system plays a vital role in innate immunity.
• Complement component 4 (C4) is a key protein in the classical and lectin complement pathways.
• C4 is encoded by two highly polymorphic loci, C4A and C4B, located within the HLA Class III region on chromosome 6.

Purpose of the Study:

• To elucidate the genetic structure and sequence of C4A and C4B genes.
• To develop specific nucleotide probes for distinguishing C4A and C4B alleles.
• To characterize the genomic organization and physical mapping of C4 loci relative to other genes in the HLA region.

Main Methods:

• Nucleotide sequencing of C4A and C4B cDNA clones.
• Synthesis of C4A and C4B specific oligonucleotide probes.
• Cosmid cloning and restriction mapping of genomic DNA.
• Nucleotide sequence analysis and hybridization studies.

Main Results:

• The complete nucleotide sequence of a C4A cDNA clone and a partial C4B cDNA clone were determined.
• Class-specific nucleotide probes differentiating C4A and C4B were synthesized.
• Three C4 loci, each approximately 16 kb, were identified and mapped 30 kb from the factor B gene.
• Characterization revealed significant similarity between the C4A and C4B genes.

Conclusions:

• The C4A and C4B genes are highly similar, reflecting their common evolutionary origin.
• The developed nucleotide probes enable specific detection and characterization of C4A and C4B alleles.
• Detailed genomic organization and mapping provide insights into the structural basis of C4 polymorphism.