The overall aim of the project is to complete a physical map of the short arm of chromosome 16. The project will allow the extension of ongoing work of the participating laboratories and will also build on, rather than duplicate, the results obtained by other laboratories with whom the groups already collaborate.
The construction of the physical map of 16p divides into three stages. The first is to connect existing contigs of cloned genomic DNA by isolating intervening genomic clones. The second is to construct a detailed physical map of the assembled contigs to allow the identification, and filling in, of any gaps. The third is to identify and map genes on to the physical map generated in the project.
Several simultaneous approaches will be used to achieve the aim. Sequence tagged sites (STSS) from the length of the short arm will be used as multiple nucleation sites to screen human genomic libraries in yeast artificial chromosomes (YACS). Isolated clones will be assembled into contigs by identifying regions of overlap. End clones will be derived from the YACs delimiting each contig and, if necessary, new markers will be isolated from gaps between contigs, to allow further rounds of chromosome walking. Libraries of smaller genomic clones, such as cosmids, will be screened if any regions are unstable as large clones. To avoid duplication of effort, contigs generated as a direct result of the project will be merged with contigs assembled by other laboratories.
Long range restriction mapping will be used to locate CpG islands and hence potential genes. Suitable genomic clones will be used in the systematic screening of cDNA libraries to identify new genes which will the be located on the map. The map generated in this project will be linked to the genetic map using existing genetic markers, and genes which have already been identified will be located on the map.
Four laboratories will be participating in this project. Three will be directly involved in isolating genomic clones and assembling a map of adjacent regions. Two will use their existing expertise to act as resource centres for the project. By combining and coordinating our efforts we will make a substantial contribution to the human genome mapping effort by completing a physical map of the short arm of chromosome 16.
Funding SchemeCSC - Cost-sharing contracts
2333 AL Leiden
OX3 9DU Oxford