This project aims to construct a detailed physical and transcriptional map of the region q24-q26 on the long arm of chromosome 10. Our primary objective is the construction of an overlapping contig of the region based on YACs identified using STSs and DNA probes already localised using other techniques for example genetic linkage mapping.
The aim of this will be to integrate both genetic and physical map data and to use this as a base for the isolation and mapping of new cDNAs and the preparation of a transcription map of the region.
This resource will be of value in the search for genes involved in malignanc and disease susceptibility that have been located in this region. A number of lines of evidence indicate that this region contains genes involved in tumour supression and progression.
For example allele loss studies have indicated that a tumour suppressor gene involved in prostate cancer maps to the band 1Oq24. Also mapping to this chromosome band are three cytochrome P450 loci of which mutations in two genes in these loci have been assosiated with susceptibility to cancer and differences in abilities to metabolise certain classes of drugs. The objectives can be summarised as follows;
1)The construction of an overlapping YAC contig based on PCR formatted STSs. 2)Quality checking of the YAC contig for chimeras and rearrangements 3)Screening of YACs for tri- and tetra- nucleotide repeats and the development of new markers for genetic mapping.
4) Mapping and ordering of all known markers in this region including the development of a long range restriction map to assist in the identification of CpG islands.
5) Isolation of cDNAs using the YACs and also cosmids cloned from regions close to known CpG islands to construct a transcription map. 6) Detailed mapping of the three cytochrome P450 loci to determine the number of active genes.
This resource would be freely available to those interested in identifying the disease associated genes in this region
Funding SchemeCSC - Cost-sharing contracts