Internet-based support for bioscience research: a collaborative genome center for human chromosome 12.

This paper describes an approach that provides Internet-based support for a genome center to map human chromosome 12, as a collaboration between laboratories at the Albert Einstein College of Medicine in Bronx, New York, and the Yale University School of Medicine in New Haven, Connecticut. Informatics is well established as an important enabling technology within the genome mapping community. The goal of this paper is to use the chromosome 12 project as a case study to introduce a medical informatics audience to certain issues involved in genome informatics and in the Internet-based support of collaborative bioscience research. Central to the approach described is a shared database (DB/12) with Macintosh clients in the participating laboratories running the 4th Dimension database program as a user-friendly front end, and a Sun SPARCstation-2 server running Sybase. The central component of the database stores information about yeast artificial chromosomes (YACs), each containing a segment of human DNA from chromosome 12 to which genome markers have been mapped, such that an overlapping set of YACs (called a "contig") can be identified, along with an ordering of the markers. The approach also includes 1) a map assembly tool developed to help biologists interpret their data, proposing a ranked set of candidate maps, 2) the integration of DB/12 with external databases and tools, and 3) the dissemination of the results. This paper discusses several of the lessons learned that apply to many other areas of bioscience, and the potential role for the field of medical informatics in helping to provide such support.

A second-generation YAC contig map of human chromosome 12.

Human chromosome 12 constitutes approximately 4.5% of the human genome and has an estimated size of 135 million base pairs (Mb). We have started to construct a high-resolution physical map of chromosome 12 as overlapping yeast artificial chromosomes (YACs), using as a foundation the first-generation physical map of this chromosome covers nearly 102 Mb of DNA and includes 426 highly polymorphic, monomorphic and gene-based markers. We also mapped 119 of the YACs, most of which are part of the physical map, by cytogenetic methods. Thus the map integrates genetic, physical and cytogenetic data and provides information about the organization of this chromosome and will help in the localization and cloning of disease-related genes. The strategy used here to generate the chromosome-12 map could be applied for the rapid construction of physical and expression maps for other human chromosomes.