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Human Molecular Genetics Advance Access published online on July 6, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh202
© 2004 by Oxford University Press
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Article

Enhancing linkage analysis of complex disorders: An evaluation of high-density genotyping

The International Multiple Sclerosis Genetics Consortium , Stephen J Sawcer 1*, Mel Maranian 1, Sarah Singlehurst 1, TaiWai Yeo 1, Alastair Compston 1, Mark J. Daly 2, Philip L. De Jager 3, Stacey Gabriel 2, David A. Hafler 3, Eric S. Lander 4, John D. Rioux 3, Emily Walsh 2, Simon G Gregory 5, Silke Schmidt 5, Margaret A. Pericak-Vance 5, Lisa Barcellos 6, Stephen L. Hauser 7, Jorge R. Oksenberg 7, Shannon J. Kenealy 8, Jonathan L. Haines 8

1 University of Cambridge Neurology Unit, Addenbrooke's, Hospital, Hills Road, Cambridge, CB2 2QQ, UK
2 The Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139-1561, USA
3 The Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139-1561, USA; Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA
4 The Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139-1561, USA; Harvard Medical School, Boston, MA 02115, USA
5 Duke University Medical Center, Center for Human Genetics, Box 3468, Durham, NC 27710, USA
6 Department of Neurology, School of Medicine, University of California San Francisco, San Francisco, CA 94143-0435, USA; Division of Epidemiology, School of Public Health, University of California at Berkeley. Berkeley, CA 94720-7360, USA
7 Department of Neurology, School of Medicine, University of California San Francisco, San Francisco, CA 94143-0435, USA
8 Center for Human Genetics Research, 519 Light Hall, Vanderbilt University Medical Center, Nashville, TN 37232-0700, USA

* To whom correspondence should be addressed. E-mail: sjs1016{at}mole.bio.cam.ac.uk.


  Abstract

To explore the potential value of recently developed high density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high density microsatellite linkage mapping set, the Illumina BeadArrayTM linkage mapping panel (version 3) and the Affymetrix GeneChip® Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP based methods (Illumina and Affymetrix) with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.


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