The human major histocompatibility complex (MHC) complement gene cluster (MCGC) is a highly variable region that is characterized by polymorphisms, variations in gene size and gene number, and associations with diseases. Deficiencies in complement C2 are either due to abolition of C2 protein synthesis by mini-deletions that caused frameshift mutations, or blocked secretion of the C2 protein by single amino acid substitutions. One, two or three C4 genes may be present in a human MCGC haplotype and these genes may code for C4A, C4B, or both. Deficiencies of C4A or C4B proteins are attributed to the expression of identical C4 isotypes or allotypes from the C4 loci, the absence or deletion of a C4 gene, 2-bp insertion at exon 29 or 1-bp deletion at exon 20 that caused frameshift mutations. The C4 genes are either 21 or 14.6 kb in size due to the presence of endogenous retrovirus HERV-K(C4) in the intron 9 of long C4 genes. A deletion or duplication of a C4 gene is always accompanied by its neighboring genes, RP at the 5′ region, and CYP21 and TNX at the 3′ region. These four genes form a genetic unit termed the RCCX module. In an RCCX bimodular structure, the pseudogene CYP21A, and partially duplicated gene segments TNXA and RP2 are present between the two C4 loci. The RCCX modular variations in gene number and gene size contributed to unequal crossovers and exchanges of polymorphic sequences/mutations, resulting in the homogenization of C4 polymorphisms and acquisitions of deleterious mutations in RP1, C4A, C4B, CYP21B and TNXB genes. RD, SKI2W, DOM3Z and RP1 are the four novel genes found between Bf and C4. RD and Ski2w proteins may be related to RNA splicing, RNA turnover and regulation of translation. The functions of Dom3z and RP1 are being investigated. The complete genomic DNA sequence between C2 and TNX is now available. This should facilitate a complete documentation of polymorphisms, mutations and disease associations for the MCGC.
C. Yung Yu
Room W208, Wexner’s Institute for Pediatric Research,
700 Children’s Drive, Columbus, OH 43205-2696 (USA)
Tel. +1 614 722 2821, Fax +1 614 722 2774
Received: Received: August 27, 1998
Accepted: September 30, 1998
Number of Print Pages : 18
Number of Figures : 4, Number of Tables : 3, Number of References : 105
Experimental and Clinical Immunogenetics
Vol. 15, No. 4, Year 1998 (Cover Date: Released February 1999)
Journal Editor: K. Bauer, Heidelberg
ISSN: 0254–9670 (print), 1421–9948 (Online)
For additional information: http://www.karger.com/journals/eci
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