Nature Genetics
4, 11 - 18 (1993)
doi:10.1038/ng0593-11
Genomic mismatch scanning: a new approach to genetic linkage mappingStanley F. Nelson1, John H. McCusker2, Mark A. Sander3, Yun Kee3, Paul Modrich4
& Patrick O. Brown1, 2, 3
1Department of Pediatrics, Stanford University Medical Center, Stanford, California 94305, USA
2Department of Biochemistry, Stanford University Medical Center, Stanford, California 94305, USA
3Howard Hughes Medical Institute, Stanford University Medical Center, Stanford, California 94305, USA
4Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA Correspondence should be addressed to P.O.B. Genomic mismatch scanning (GMS) is a new method of genetic linkage analysis that does not require conventional polymorphic markers or gel electrophoresis. GMS is ideally suited to affected−relative−pair mapping. DNA fragments from all regions of identity−by−descent between two relatives are isolated based on their ability to form extensive mismatch−free hybrid molecules. The genomic origin of this selected pool of DNA fragments is then mapped in a single hybridization step. Here we demonstrate the practicality of GMS in a model organism, Saccharomyces cerevisiae. GMS is likely to be applicable to other organisms, including humans, and may be of particular value in mapping complex genetic traits.
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