The aims of this proposal can be grouped into three main areas: (i) a continuation of theoretical work associated with the transmission/ disequilibrium test (TDT), (ii) to extend the TDT concept to new forms of data, especially that deriving from the technique of genomic mismatch scanning. (GMS), and (iii) to complete work in ascertainment sampling and genome reconstruction. (i) The transmission/disequilibrium test (TDT) has proved to be a major tool in the quest to find linkage between disease and marker loci and associations between disease and marker alleles. Recently an extension of the test, called the S-TDT (sib-TDT), has been obtained, which allows testing when information concerning the marker locus genotype of parents of affected children is not available. A method by which TDT and S-TDT data can be combined into one overall test was also found. Many further aspects of this research will be completed. (ii) Data have already been obtained using the GMS technique showing, for any two individuals affected by some disease, those parts of the genome which are IBD (identical by descent) in these two individuals. Aggregated over many such pairs, these data show clustering of IBD regions which are therefore candidate regions for loci for the disease genes. Since the data came from unrelated individuals, a TDT-like statistical analysis testing this possibility is needed and will be obtained. Both this aim and that in (i) focus on the attempt to locate genes causing diseases. (iii) Work in ascertainment sampling and genome reconstruction using clones and anchors will be completed. The theory for the latter is similar to that for the GMS technique of aim (ii).
