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Investigation of seven proposed regions of linkage in multiple sclerosis: an American and French collaborative study

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Abstract.

Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.

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Acknowledgements.

We thank the patients and their families, without whom this study would not have been possible. This work was supported by grants from the National Multiple Sclerosis Society (NMSS) (S.L.H., J.R.O.), NIH grants NS32830 (J.L.H., M.P.V.), and NS26799 (S.L.H.), the Mathers Foundation (S.L.H.), and the Nancy Davis Foundation (S.L.H.). This work was also supported by funding from ARSEP, INSERM, FRM (Action 2000), AFM (Genethon), CIC Pitie-Salpetriere, and Groupe Malakoff. All research was in compliance with the current laws of the countries in which they were performed.

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Authors and Affiliations

  1. Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA

    Margaret A. Pericak-Vance & Jackie B. Rimmler

  2. Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, USA

    Jonathan L. Haines & Melissa E. Garcia

  3. Department of Neurology, University of California, San Francisco, California, USA

    Jorge R. Oksenberg, Lisa F. Barcellos, Robin Lincoln & Stephen L. Hauser

  4. Federation de Neurologie and INSERM U546, Groupe Hospitalier and Faculte de Medecine Pitie-Salpetriere, Paris, France

    Isabelle Cournu-Rebeix, Ariele Azoulay-Cayla, Olivier Lyon-Caen & Bertrand Fontaine

  5. Federation de Neurologie and CNRS UPR 2163, Centre Hospitalier Universitaire Purpan, Toulouse, France

    Emmanuelle Duhamel, Helene Coppin, David Brassat, Marie-Paule Roth & Michel Clanet

  6. Service de Neurologie and Laboratoires d’Immunologie et d’Epidemiologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France

    Mehdi Alizadeh, Jacqueline Yaouanq, Erwann Quelvennec, Gilbert Semana & Gilles Edan

  7. INSERM U535, Centre Hospitalier Universitaire, Le Kremlin-Bicetre, France

    Marie-Claude Babron, Emmanuelle Genin & Francoise Clerget-Darpoux

  8. Center for Human Genetics Research, Vanderbilt University Medical Center, 519 Light Hall, Nashville, TN 37232–0700, USA

    Jonathan L. Haines

Authors
  1. Margaret A. Pericak-Vance
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  2. Jackie B. Rimmler
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  3. Jonathan L. Haines
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  4. Melissa E. Garcia
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  5. Jorge R. Oksenberg
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  6. Lisa F. Barcellos
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  7. Robin Lincoln
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  8. Stephen L. Hauser
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  9. Isabelle Cournu-Rebeix
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  10. Ariele Azoulay-Cayla
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  11. Olivier Lyon-Caen
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  12. Bertrand Fontaine
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  13. Emmanuelle Duhamel
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  14. Helene Coppin
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  15. David Brassat
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  16. Marie-Paule Roth
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  17. Michel Clanet
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  18. Mehdi Alizadeh
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  19. Jacqueline Yaouanq
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  20. Erwann Quelvennec
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  21. Gilbert Semana
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  22. Gilles Edan
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  23. Marie-Claude Babron
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  24. Emmanuelle Genin
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  25. Francoise Clerget-Darpoux
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Corresponding author

Correspondence to Jonathan L. Haines.

Additional information

I. Cournu-Rebeix, E. Duhamel, M. Alizadeh, and M.-Claude Babron contributed equally to this work.

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Pericak-Vance, M.A., Rimmler, J.B., Haines, J.L. et al. Investigation of seven proposed regions of linkage in multiple sclerosis: an American and French collaborative study. Neurogenetics 5, 45–48 (2004). https://doi.org/10.1007/s10048-003-0163-y

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  • DOI: https://doi.org/10.1007/s10048-003-0163-y

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