Mutation and diversity in copy number variable genes. (360G-Wellcome-087663_Z_08_Z)

The research will develop methods pioneered in the department to precisely analyse sequence variation between different copy number haplotypes of the FCGR3 gene, and to infer recurrent ectopic recombination breakpoints between the FCGR3A and FCGR3B repeats. This information will inform assays designed to assess the frequency of de novo deletion and the amount of somatic copy number variation at this locus. Key goals are: 1. A sequence-level catalogue of coding and non-coding sequence variatio n of the FCGR3A and FCGR3B repeat haplotypes using genome fractionation by pulsed-field gel electrophoresis followed by high-throughput sequencing, distinguishing differences between paralogues from allelic differences. 2. Identification of historical ectopic recombination breakpoints in 45 deletion copy number haplotypes from this sequence catalogue. 3. Development of an assay to specifically amplify de novo deletion haplotypes from genomic DNA. 4. Use this assay to determine frequency of d e novo deletion in sperm.