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© 1995 Oxford University Press

RESEARCH-ARTICLE

Comparison of the positional cloning methods used to isolate the BRCA1 gene

Keith Harshman1,*, Russell Bell1, Judith Rosenthal1, Harold Katcher1, Yoshio MlKl2, Jeff Swenson2, Zahra Gholami1, Cheryl Frye1, Wei Ding1, Priya Dayananth1, Ken Eddington1, Franklin H. Norris3, Pamela K. Bristow3, Robert Phelps1, Thomas Haltier1, Steven Stone1, Daniel Shaffer1, Steven Bayer1, Charles Hussey1, Thanh Tran1, Katherine Richardson3, Brad Dehoff3, Mei Lai3, Paul R. Rosteck, Jr3, Mark H. Skolnick1,2, Donna Shattuck-Eidens1 and Alexander Kamb1

1Myriad Genetics, Inc. 390 Wakara Way, Salt Lake City, UT 84108 2Department of Medical Informatics, University of Utah Medical Center Salt Lake City, UT 84132 3Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center Indianapolis, IN 46285. USA

*To whom correspondence should be addressed

Received April 12, 1995; Revised April 28, 1995; Accepted April 28, 1995

A critical step in positional cloning is the identification of candidate genes from a large, genetically defined region. Candidate gene isolation by hybrid selection, genomic sequencing, and direct cDNA library screening identified 45 candidate gene fragments (CGFs) from a 600 kb genomic region that contains the BRCA1 gene. These CGFs define a minimum of 15 genes, six of which are newly localized to the BRCA1 region. We present an analysis of the efficiency and the sequences generated for each of these methods. We also compare our CGF set to those reported for the BRCA1 region by three other groups, revealing a surprising lack of overlap among the sets.


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