Immunogenetics

, Volume 57, Issue 11, pp 805–815 | Cite as

Extensive genomic and functional polymorphism of the complement control proteins

  • Craig A. McLure
  • Joseph F. Williamson
  • Louise A. Smyth
  • Suraksha Agrawal
  • Susan Lester
  • John A. Millman
  • Peter J. Keating
  • Brent J. Stewart
  • Roger L. Dawkins
Original Paper

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).

Keywords

Ancestral haplotypes Complement control proteins Autoimmunity Genomic matching technique Regulators of complement activation 

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

Notes

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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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Craig A. McLure
    • 1
    • 2
  • Joseph F. Williamson
    • 1
  • Louise A. Smyth
    • 1
  • Suraksha Agrawal
    • 3
  • Susan Lester
    • 1
    • 4
  • John A. Millman
    • 1
    • 5
  • Peter J. Keating
    • 1
  • Brent J. Stewart
    • 1
    • 2
  • Roger L. Dawkins
    • 1
    • 2
  1. 1.CY O’Connor ERADE VillageWestern AustraliaAustralia
  2. 2.Centre for Molecular Immunology and Instrumentation, University of Western AustraliaWestern AustraliaAustralia
  3. 3.Department of Medical GeneticsSanjay Gandhi Institute of Medical SciencesLucknowIndia
  4. 4.Arthritis Research LaboratoryHanson InstituteAdelaide, South AustraliaAustralia
  5. 5.TAFEWA Swan CampusBentley, Western AustraliaAustralia

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