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The genetic complexity and protein polymorphism of complement c4 in health and disease

Yang, Yan
http://rave.ohiolink.edu/etdc/view?acc_num=osu1080242341

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Medical Microbiology and Immunology.
The two isotypes of immune effector proteins complement component C4, C4A and C4B, exhibit different biological functions. The number of C4 genes present in a diploid genome varies from 2 to 6 among different individuals. The variation of C4 gene dosage is always concurrent with three other flanking genes, including RP, CYP21 and TNX. The size of C4 genes can be long (21 kb) or short (14.6 kb), which differs in 6.4 kb due to the presence or absence of an endogenous retroviral sequence in intron 9. Complete or partial deficiency of C4A has been observed to be a risk factor for systemic lupus erythematosus (SLE). However, a deeply ingrained but inaccurate “two-locus” model of human C4 genes had impeded advances on epidemiological studies of C4 and diseases. The first objective of this dissertation was to determine the genetic complexity and protein polymorphism of C4. It was observed that there were good correlations between the number of long C4 genes with C4A protein levels, and the number of short C4 genes with C4B protein levels. The short C4B gene in the second locus not only increased the C4B protein level, but also slightly increased the C4A protein levels coded by the long C4A gene of the first locus. The second objective was to determine the molecular basis of C4 mutations from complete C4 deficiency subjects. Novel C4 mutations were discovered in seven complete deficient subjects. Sequence-specific polymerase chain reaction strategies were created for rapid screenings of known C4 mutations in human populations. The third objective was to study variations of C4 gene dosages and protein polymorphisms in Caucasian and Black SLE patients. When compared with case controls, both Caucasian and Black SLE patients had increased frequencies in deficiencies of total C4 and C4A genes. Protein levels of total C4, C4A and C4B decreased in SLE patients within the same gene dosage groups. The low protein levels of total C4 and C4A in SLE may result from low gene dosages in total C4 and/or C4A, C4A gene mutations, low C4 protein expression, and/ or high C4 protein consumption.
Chack-Yung Yu (Advisor)
230 p.
Health Sciences, Immunology
complement C4; systemic lupus erythematosus; sequence-specific polymerase chain reaction

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Citations

  • Yang, Y. (2004). The genetic complexity and protein polymorphism of complement c4 in health and disease [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1080242341

    APA Style (7th edition)

  • Yang, Yan. The genetic complexity and protein polymorphism of complement c4 in health and disease. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1080242341.

    MLA Style (8th edition)

  • Yang, Yan. "The genetic complexity and protein polymorphism of complement c4 in health and disease." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1080242341

    Chicago Manual of Style (17th edition)

osu1080242341
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This open access ETD is published by The Ohio State University and OhioLINK.