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High-resolution human genome structure by single-molecule analysis
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High-resolution human genome structure by single-molecule analysis

  1. David C. Schwartza,1
  1. aThe Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics and Biotechnology Center, University of Wisconsin, 425 Henry Mall, Madison, WI 53706-1580;
  2. bDepartment of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089-2910;
  3. cDepartment of Statistics, University of Wisconsin, 1300 University Avenue, Madison, WI 53706-1510;
  4. dDepartment of Genome Sciences, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195-5065;
  5. eDepartment of Biostatistics and Medical Informatics, University of Wisconsin, 1300 University Avenue, Madison, WI 53706-1510;
  6. fDepartment of Animal Science, Department of Biological Sciences, Mississippi State University, 130 Harned Hall, Lee Boulevard, Mississippi State, MS 39762-9698;
  7. gDepartment of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213-2536; and
  8. hDepartment of Computer Sciences, University of Wisconsin, 1210 West Dayton Street, Madison, WI 53706-1685
  1. Edited* by David E. Housman, Massachusetts Institute of Technology, Cambridge, MA, and approved May 6, 2010 (received for review December 17, 2009)


Variation in genome structure is an important source of human genetic polymorphism: It affects a large proportion of the genome and has a variety of phenotypic consequences relevant to health and disease. In spite of this, human genome structure variation is incompletely characterized due to a lack of approaches for discovering a broad range of structural variants in a global, comprehensive fashion. We addressed this gap with Optical Mapping, a high-throughput, high-resolution single-molecule system for studying genome structure. We used Optical Mapping to create genome-wide restriction maps of a complete hydatidiform mole and three lymphoblast-derived cell lines, and we validated the approach by demonstrating a strong concordance with existing methods. We also describe thousands of new variants with sizes ranging from kb to Mb.


  • 1To whom correspondence should be addressed. E-mail: dcschwartz{at}
  • Author contributions: B.T., M.S.W., S.G., S.R., D.S., A.V., and D.C.S. designed research; B.T., K.P., S.R., C.L., and M.K.-F. performed research; B.T., M.S.W., S.G., K.P., D.S., A.V., C.C., J.M.K., S.K., R.R., D.F., M.A.N., E.E.E., M.K.-F., U.S., and M.L. contributed new reagents/analytic tools; B.T., M.S.W., S.G., K.P., S.Z., S.R., D.S., A.V., C.C., J.M.K., M.A.N., E.E.E., and D.C.S. analyzed data; and B.T., S.G., S.R., and D.C.S. wrote the paper.

  • The authors declare no conflict of interest.

  • *This Direct Submission article had a prearranged editor.

  • This article contains supporting information online at

    Freely available online through the PNAS open access option.

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