The central goal of this proposal is to provide a near complete description of the SNPs within a defined region and to build a database that will provide for the rapid and effective dissemination of the resultant data to the scientific community. This study will focus on the class I region within the major histocompatibility complex (MHC). Our target for SNP discovery consists of a 2.3 megabase segment that includes all of the HLA class I genes. We are near completion of a project to determine the nucleotide sequence of this contiguous 2.3 Mbp segment, thus making available a template for SNP discovery and a team of highly trained genomic scientists. We also have well established informatics capabilities from our genomic work and will capitalize on this and strong institutional support in order to deliver SNP data to the scientific community. To reach these goals we propose to accomplish the following specific aims: 1) To identify a large proportion of the SNPs in the 2.3 Mbp HLA class I region and 2) To develop a database designed to track, monitor and disseminate data and information associated with the HLA SNP project.
This aim will include four major categories of development: i) data capture, ii) statistical process control, iii) analysis, and iv) presentation. We will collaborate with an independent group to develop needed software and capitalize on ongoing efforts at the FHCRC to build a strong informatics software and hardware support base. As the MHC contains the most polymorphic loci resident in the human genome, a catalogue of HLA SNPs has the potential for a broad impact on the scientific research community. The applicability extends from genetic matching of donor and recipient in unrelated transplants, to explaining the many MHC disease associations that remain unsolved today, and further to basic questions in anthropology and evolutionary biology and indeed to genomic sciences. An HLA SNP data set will help define new approaches to treating disease, interpreting population studies, and extending the abilities for gene discovery and understanding gene function.
| Geraghty, Daniel E; Daza, Riza; Williams, Luke M et al. (2002) Genetics of the immune response: identifying immune variation within the MHC and throughout the genome. Immunol Rev 190:69-85 |
