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The immunoglobulin heavy chain and disease association: application to pemphigus vulgaris

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Abstract

Genes involved in the immune response are generally encoded from a complex cluster of gene segments. Studies of the association of diseases with such genes require well-defined genetic markers throughout the selected region. A set of 15 polymorphic loci that span 1500 kb of the immunoglobulin heavy chain (IGH) complex, 8 in the variable (VH) region and 7 in the constant (CH) region, were selected for the study of disease association. We present a protocol for the use of multiple immunoglobulin heavy chain (IGH) polymorphisms for general application in disease association studies. No microsatellite repeat markers are available for this region. To demonstrate the applicability of this approach, we have examined these IGH polymorphisms in families with individuals affected with pemphigus vulgaris (PV), an autoimmune dermatologie disease. Allele frequencies in 12 patients with PV were compared with those found in their spouses, and with those in a white Canadian control population. A significant difference was found between PV patients and both control groups for the presence of the VH gene VH3f-R4, and possibly for the absence of VH3f-R3, suggesting the possibility of susceptibility factors in these regions. Examination of the frequencies of the IGH region Cγ-haplotypes of PV patients indicated that, while the patients did not differ significantly from their spouses (χ2=1.79), both groups were found to differ significantly from the white Canadian control group (χ2=10.10), emphasizing the importance of matching the ethnic background of controls with that of the patient test group in disease association studies. Unexpectedly, two patients had large deletions of genes in the IGH constant region, which could play a role in the development of PV and require further investigation.

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Author notes

  1. Michael A. Walter

    Present address: University of Alberta, Room 659, 6th floor, Heritage Building, T6G 2S3, Edmonton, Alberta, Canada

Authors and Affiliations

  1. Research Institute, The Hospital for Sick Children, Toronto

    William T. Gibson, Michael A. Walter & Diane W. Cox

  2. Departments of Paediatrics and Molecular and Medical Genetics, University of Toronto, M5G 1X8, Toronto, Ontario, Canada

    William T. Gibson, Michael A. Walter & Diane W. Cox

  3. The Center for Blood Research, Boston, Massachusetts, USA

    Chester A. Alper

  4. Department of Dermatology, Boston University, School of Medicine, Boston, Massachusetts, USA

    A. Razzaque Ahmed

Authors
  1. William T. Gibson
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  2. Michael A. Walter
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  3. A. Razzaque Ahmed
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  4. Chester A. Alper
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  5. Diane W. Cox
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Gibson, W.T., Walter, M.A., Ahmed, A.R. et al. The immunoglobulin heavy chain and disease association: application to pemphigus vulgaris. Hum Genet 94, 675–683 (1994). https://doi.org/10.1007/BF00206963

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  • DOI: https://doi.org/10.1007/BF00206963

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