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Extensive genomic and functional polymorphism of the complement control proteins

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Abstract

Using combinations of genomic markers, we describe more than 20 distinct ancestral haplotypes (AH) of complement control proteins (CCPs), located within the regulators of complement activation (RCA) alpha block at 1q32. This extensive polymorphism, including functional sites, is important because CCPs are involved in the regulation of complement activation whilst also serving as self and viral receptors. To identify haplotypes, we used the genomic matching technique (GMT) based on the pragmatic observation that extreme nucleotide polymorphism is packaged with duplicated sequences as polymorphic frozen blocks (PFB). At each PFB, there are many alternative sequences (haplotypes) which are inherited faithfully from very remote ancestors. We have compared frequencies of RCA haplotypes and report differences in recurrent spontaneous abortion (RSA) and psoriasis vulgaris (PV).

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Abbreviations

AH:

Ancestral haplotype

ARL-C:

Arthritis Research Laboratory controls

CCP:

Complement control proteins

CR1:

Complement receptor 1

CR1-L:

Complement receptor 1-like

CR2:

Complement receptor 2

GMT:

Genomic matching technique

HCT:

Haemochromatosis

HE:

Haplospecific geometric element

Indels:

Insertions/deletions

MCP:

Membrane cofactor protein

MCP-L:

Membrane cofactor protein-like

MHC:

Major histocompatibility complex

PCR:

Polymerase chain reaction

PFB:

Polymorphic frozen block

PV:

Psoriasis vulgaris

RCA:

Regulators of complement activation

RSA:

Recurrent spontaneous abortion

RSA-C:

Recurrent spontaneous abortion controls

RSA-P:

Recurrent spontaneous abortion patients

SA:

Suraksha Agrawal

SLE:

Systemic lupus erythematosus

SS:

Sjogren’s syndrome

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Acknowledgments

We are grateful to Dr. D Sayer and Royal Perth Hospital for the sequencing of the products, Dr. Peter Kesners for advice and Ms. Wendy Ford for administration. The samples designated RSA-C and RSA-P are from the Sanjay Gandhi Institute of Medical Sciences (SA). Those designated ARL-C, SLE-P and SS are from the Arthritis Research Laboratory, Hanson Institute (SL) with acknowledgements to Dr. Maureen Rischmueller of Rheumatology, Queen Elizabeth Hospital, Adelaide. The HCT and PV samples were described previously (Korendowych et al. 2002). Supported by Australian Research Council, CY O’Connor Village Foundation and Genetic Technologies, Fitzroy, Victoria 3065, Australia. Collectively, the authors associated with the CY O’Connor ERADE Village have an interest in Genetic Technologies.

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Authors and Affiliations

  1. CY O’Connor ERADE Village, P.O. Box 5100, Canning Vale, Western Australia, 6155, Australia

    Craig A. McLure, Joseph F. Williamson, Louise A. Smyth, Susan Lester, John A. Millman, Peter J. Keating, Brent J. Stewart & Roger L. Dawkins

  2. Centre for Molecular Immunology and Instrumentation, University of Western Australia, Nedlands, Western Australia, 6907, Australia

    Craig A. McLure, Brent J. Stewart & Roger L. Dawkins

  3. Department of Medical Genetics, Sanjay Gandhi Institute of Medical Sciences, Lucknow, 226014, India

    Suraksha Agrawal

  4. Arthritis Research Laboratory, Hanson Institute, Frome Road, Adelaide, South Australia, 5000, Australia

    Susan Lester

  5. TAFEWA Swan Campus, Hayman Road, Bentley, Western Australia, 6102, Australia

    John A. Millman

Authors
  1. Craig A. McLure
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  2. Joseph F. Williamson
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  3. Louise A. Smyth
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  4. Suraksha Agrawal
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  5. Susan Lester
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  6. John A. Millman
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  7. Peter J. Keating
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  8. Brent J. Stewart
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  9. Roger L. Dawkins
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Corresponding author

Correspondence to Roger L. Dawkins.

Additional information

Nucleotide sequence data reported are available in the GenBank database under the accession numbers DQ007054–DQ007076. Manuscript number 0408 of the Centre for Molecular Immunology and Instrumentation of the University of Western Australia and the CY O’Connor ERADE Village

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McLure, C.A., Williamson, J.F., Smyth, L.A. et al. Extensive genomic and functional polymorphism of the complement control proteins. Immunogenetics 57, 805–815 (2005). https://doi.org/10.1007/s00251-005-0049-2

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  • DOI: https://doi.org/10.1007/s00251-005-0049-2

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