Inherited structural polymorphism of the fourth component of human complement.

Area of Science:

• Immunogenetics
• Human Molecular Genetics
• Complement System Biology

Background:

• The human fourth component of complement (C4) is crucial for immune response.
• Understanding C4 genetic polymorphism is essential for studying immune-related diseases.
• Previous studies suggested complexity in C4 gene structure and inheritance.

Purpose of the Study:

• To investigate the genetic polymorphism of human C4.
• To delineate the distinct genetic loci for C4 and their allelic variants.
• To examine the linkage between C4 loci and other genes within the major histocompatibility complex.

Main Methods:

• Agarose gel electrophoresis of neuraminidase-treated plasma was employed.
• Analysis focused on separating and identifying products of C4 genetic loci.
• Linkage analysis was performed with C2 and BF loci within the human histocompatibility complex.

Main Results:

• High polymorphism was observed in human C4, with clear separation of C4A and C4B products.
• At least six variants and a deletion allele were identified at the C4A locus, and two variants and a deletion at the C4B locus.
• Close linkage without recombination was found between C4A and C4B loci, enabling definition of C4AB haplotypes and their linkage to C2 and BF loci.

Conclusions:

• Direct evidence supports two distinct, closely linked genetic loci for human C4 (C4A and C4B).
• These C4 loci are situated within the major histocompatibility complex on chromosome 6.
• The identified C4 haplotypes and their frequencies provide a foundation for future genetic association studies.