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Vol. 9, Issue 10, 994-1001, October 1999

RESOURCE
Human Genome Anatomy: BACs Integrating the Genetic and Cytogenetic Maps for Bridging Genome and Biomedicine

Julie R. Korenberg,1,6 Xiao-Ning Chen,1 Zhiguang Sun,1 Zheng-Yang Shi,1 Shaowu Ma,1 Eddy Vataru,1 Dean Yimlamai,1 Jean S. Weissenbach,2 Hiroaki Shizuya,3 Melvin I. Simon,3 Sebastian S. Gerety,4 Huy Nguyen,4 Irina S. Zemsteva,4 Lester Hui,4 James Silva,4 Xiaoyun Wu,4 Bruce W. Birren,4 and Thomas J. Hudson4,5

1 Medical Genetics Birth Defects Center, Cedars-Sinai Medical Center and the Department of Human Genetics, University of California at Los Angeles, (UCLA), Los Angeles, California 90048 USA; 2 Genoscope, Centre National De Sequenceage, 91006 Evry Cedex, France; 3 Division of Biology, California Institute of Technology, Pasadena, California USA; 4 Whitehead Institute/MIT Center for Genome Research Whitehead Institute for Biomedical Research, Cambridge, Massachusetts USA; 5 Montreal General Hospital Research Institute, McGill University, Montreal, H3G 1A4 Canada

Human genome sequencing is accelerating rapidly. Multiple genome maps link this sequence to problems in biology and clinical medicine. Because each map represents a different aspect of the structure, content, and behavior of human chromosomes, these fundamental properties must be integrated with the genome to understand disease genes, cancer instability, and human evolution. Cytogenetic maps use 400-850 visible band landmarks and are the primary means for defining prenatal defects and novel cancer breakpoints, thereby providing simultaneous examination of the entire genome. Recent genetic, physical, and transcript maps use PCR-based landmarks called sequence-tagged sites (STSs). We have integrated these genome maps by anchoring the human cytogenetic to the STS-based genetic and physical maps with 1021 STS-BAC pairs at an average spacing of ~1 per 3 Mb. These integration points are represented by 872 unique STSs, including 642 polymorphic markers and 957 bacterial artificial chromosomes (BACs), each of which was localized on high resolution fluorescent banded chromosomes. These BACs constitute a resource that bridges map levels and provides the tools to seamlessly translate questions raised by genomic change seen at the chromosomal level into answers based at the molecular level. We show how the BACs provide molecular links for understanding human genomic duplications, meiosis, and evolution, as well as reagents for conducting genome-wide prenatal diagnosis at the molecular level and for detecting gene candidates associated with novel cancer breakpoints.

6   Corresponding author.

9:994-1001 ©1999 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/99 $5.00
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