One of the goals of the human genome initiative is to create linkage maps for all human chromosomes with an average resolution of I cM. Such maps require large scale collaborations and explicit attention to the problems of data management, methodologies for map construction and widespread locus distribution. The Centre d'Etude du Polymorphisme Humain (CEPH) coordinates an international effort to genetically map the human genome. CEPH provides cellular DNA from each member of a reference panel of 40 large nuclear families/pedigrees to 70 collaborating laboratories, where genotypes for over 1,000 polymorphic DNA loci have already been determined. These genotypes are incorporated by CEPH into a database that is shared by all collaborators. By having multiple investigators contribute data on the same set of families, rapid accumulation of the genotypes necessary to construct primary genetic maps of human chromosomes with fine structure resolution can be obtained. This proposal will establish consortium committee meetings for each human chromosome to bring together a subset of investigators with particular expertise on each individual human chromosome. The committee heads will collect individual data for each locus/probe/polymorphism combination reported for their particular chromosome, do initial analysis to identify incompatibilities or possible genotyping errors and provide data to all committee members for review and preliminary multipoint map construction. Subsequently, a committee meeting will be held to discuss the details of linkage map construction methodologies, resolve errors in genotyping, consider additions of relevant new systems, and establish cri- teria for selection of loci to be included in maps of varying degrees of resolution. Following the committee meeting, updates and corrections in the database will then be redistributed to committee members for final map construction and submission to the chairman. A manuscript will be written, using the input of all committee members and subsequently published as the consortium linkage map for that particular chromosome. As each consortium map is published, previously unpublished genotypic data will be released to the scientific community.
