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Genomic organization of human complement protein C8α and further examination of its linkage to C8β

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Abstract

Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact to form the cytolytic C5b-9 complex on target membranes. It is composed of three nonidentical subunits (C8α, C8β, C8γ) encoded by separate genes. C8α and C8β are linked on chromosome 1p32, whereas C8γ is located on 9q22.3-q32. In this study, overlapping genomic clones were isolated and used to decipher the organization of the human C8α gene. The gene contains at least 11 exons spanning ∼70kb of DNA. When compared to C6, C8β and C9, there is a remarkable similarity in genomic organization, consistent with amino acid sequence comparisons that suggest these proteins are ancestrally related. Regions of each protein that are structurally similar are encoded in exons of correspondingly similar lengths with highly conserved boundaries and phases. Availability of genomic sequence also facilitated a more detailed analysis of C8α and C8β linkage. Based on analysis of genomic digests with cDNA probes, the loci were previously reported to be physically linked (< 2.5kb) and in a 5′α-β 3′ orientation. In the present study, results obtained using exon-specific probes indicate the loci are not as closely linked as initially believed. Furthermore, they suggest that cDNA probes used earlier yielded misleading information because they encode exons that are distributed across large segments of genomic DNA.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry and the School of Medicine, University of South Carolina, 29208, Columbia, SC, USA

    Gregory A. Michelotti, James V. Snider & James M. Sodetz

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  1. Gregory A. Michelotti
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  2. James V. Snider
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  3. James M. Sodetz
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Michelotti, G.A., Snider, J.V. & Sodetz, J.M. Genomic organization of human complement protein C8α and further examination of its linkage to C8β. Hum Genet 95, 513–518 (1995). https://doi.org/10.1007/BF00223862

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  • DOI: https://doi.org/10.1007/BF00223862

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