chain atoms); upon cleavage, this unique thionolactone ring structure becomes exposed at the surface of the new c4b protein. because of proximity to the microbial surface, some portion of the released c4b proteins, with this reactive thionolactone, react with nucleophilic amino acid side chains and other groups on the foreign microbe's cell surface, resulting in covalent attachment of the slightly modified c4b protein to the cell surface, via the original glx residue of c4. c4b has further functions. it interacts with protein c2; the same protease invoked earlier, c1s, then cleaves c2 into two parts, termed c2a and c2b, with c2b being released, and c2a remaining in association with c4b; the c4b-c2a complex of the two proteins then exhibits a further system-associated protease activity toward protein c3 (cleaving it), with subsequent release of both proteins, c4b and c2a, from their complex (whereupon c4b can bind another protein c2, and conduct these steps again). because c4b is regenerated, and a cycle is created, the c4b-c2a complex with protease activity has been termed the c3 convertase. protein 4b can be further cleaved into 4c and 4d. clinical significance model of common structural genes and their possible contribution to the development of schizophrenia (as thoroughly defined in the sekar et al. article) although other diseases (i.e. systemic lupus erythematosus) have been implicated, the c4 gene is also being investigated for the role it may play in schizophrenia risk and development. in the wu et al. study, they utilized the real-time polymerase chain reaction (rt-pcr) as an assay to determine the copy number variance (cnv) or genetic diversity of c4. accordingly, with these results, future prognoses, flares, and remissions will become more feasible to determine. the results basically show copy number variants as a mechanism to effect genetic diversity. as discussed before, the different phenotypes allowed for by the varying genetic variety of complement c4 include a wide range of plasma or serum c4 proteins among two isotypes—c4a and c4b—with multiple protein allotypes that can have unique physiological functions. cnvs are sources of inherent genetic diversity and are engaged in gene-environment interaction. cnvs (and associated polymorphisms) play a role in filling in the gap towards understanding the genetic basis of quantitative traits and the different susceptibilities to autoimmune and neurobiological diseases. substantial data from all over the world has been collected and analyzed to determine that schizophrenia, indeed, has a strong genetic relationship with a region in the mhc locus on chromosome arm 6. data and information collected internationally can shed light onto the mysteries of schizophrenia. sekar et al. analyzed single nucleotide polymorphisms (snp) of 40 cohorts in 22 countries, in total adding up to nearly 29,000 cases. they found out two features: 1) a great number of snps reaching only 2mb across the end, 2) peak of association centered at c4, predicting that c4a expression levels is most strongly correlated with schizophrenia. in addition, they have discovered a mechanism by which schizophrenia could arise from the genetic predisposition of the human complement c4. as shown in figure 1, four common structural variations discovered in genome-wide association studies (gwas) studies have pointed to the high turnout of schizophrenia. possibly, the higher levels of expression of c4 protein due to pattern of variants of the c4 gene, allows for the unwanted increase in synaptic pruning (an effect produced by the effector proteins of the complement system in which the c4 partakes).