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Linkage-disequilibrium mapping without genotyping

Nature Genetics volume 18, pages 225–230 (1998)Cite this article

Abstract

Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of GMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.

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Authors and Affiliations

  1. Divisions of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Vivian G. Cheung & Jonathan Bandong

  2. Departments of Pathology, University of California, Los Angeles, California, 90095, USA

    Jeffrey P. Gregg

  3. Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Kathryn J. Gogolin-Ewens & Richard S. Spielman

  4. Divisions of Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Charles A. Stanley & Lester Baker

  5. Department of Human Genetics, RoswellPark Cancer Institute, Buffalo, New York, 14263, USA

    Michael J. Higgins, Norma J. Nowak & Thomas B. Shows

  6. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Warren J. Ewens

  7. Departments of Pediatrics and Biological Chemistry, University of California, Los Angeles, California, 90095, USA

    Stanley F. Nelson

Authors
  1. Vivian G. Cheung
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  2. Jeffrey P. Gregg
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  3. Kathryn J. Gogolin-Ewens
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  4. Jonathan Bandong
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  5. Charles A. Stanley
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  6. Lester Baker
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  7. Michael J. Higgins
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  10. Warren J. Ewens
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  11. Stanley F. Nelson
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  12. Richard S. Spielman
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Cheung, V., Gregg, J., Gogolin-Ewens, K. et al. Linkage-disequilibrium mapping without genotyping. Nat Genet 18, 225–230 (1998). https://doi.org/10.1038/ng0398-225

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