Human genome anatomy: BACs integrating the genetic and cytogenetic maps for bridging genome and biomedicine

Human genome sequencing is accelerating rapidly. Multiple genome maps link this sequence to problems in biology and clinical medicine. Because each ma p 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 evolutio n. Cytogenetic maps use 400-850 visible band landmarks and are the primary means for defining prenatal defects and novel cancer breakpoints, thereby p roviding simultaneous examination of the entire genome. Recent genetic, phy sical, and transcript maps use PCR-based landmarks called sequence-tagged s ites (STSs), We have integrated these genome maps by anchoring the human cy togenetic to the STS-based genetic and physical maps with 1021 STS-BAC pair s at an average spacing of similar to 1 per 3 Mb. These integration points are represented by 872 unique STSs, including 642 polymorphic markers and 9 57 bacterial artificial chromosomes (BACs) each of which was localized on h igh resolution fluorescent banded chromosomes. These BACs constitute a reso urce that bridges map levels and provides the tools to seamlessly translate questions raised by genomic change seen at the chromosomal level into answ ers based at the molecular level. We show how the BACs provide molecular li nks for understanding human genomic duplications, meiosis, and evolution, a s well as reagents for conducting genome-wide prenatal diagnosis at the mol ecular level and for detecting gene candidates associated with novel cancer breakpoints.