This application aims to establish a core informatics resource for the Killer-cell ImmunogTobulin-like Receptors (KIR) research community and create an essential tool for the collaborations associatedwith the integrated program on """"""""NK cells their receptors and unrelated donor transplant"""""""". The applicant will generate and develop a publicly accessible database of KIR cDNA and genomic sequences; (of which tnere are currently in excess of 100 known) derived from the literature, generalist DNA sequence databases and from direct submission to the KIR sequence database. Software tools will be developed for the direct submission, analysis, manipulation and retrieval of sequences; laboratory based assays for KIR genotyping will be standardized; naplotype and genotype data will be generated and integrated into the database Laboratory studies will also be carried out to better characterize and extend existing KIR allele sequences, and to validate published or submitted sequences. The applicant is Rapporteur and Chairman of IUIS Subcommittee on KIR nomenclature under the auspices of the WHO Nomenclature Committee for factors of the HL.A system. The database will be developed on a Unix platform based around software written by Oracle so as to maintain compatibility with other public databases. Tools for sequence handling will be developed using PERL and will be based on similar tools established previously for handling HLA sequences. The database will be made freely available to users via the world wide web Data-mining of sequence repositorieswill require systematic data-cleaning and confirmation of sequence identity before alleles can be formally named. In addition to standardized KIR sequence alignments, KIR sequence files will also be madeavailable in a number of different formats including FASTA, PIR and MSF for remote download ng by ftp. In time this resource will help in determining the significance of KIR gene variation to the outcomes of allogeneic hematopoietic cell transplantation.
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