The broad aim of the proposed research is to attack theoretical questions arising in various practical disease-related issues, especially in connection with linkage analysis (of putative disease loci to markers), ascertainment corrections (usually associated with disease data) and the physical mapping of gene loci using anchored clones.
Some specific aims of the proposed research are: (i) To continue work on the transmission distortion test (TDT) described elsewhere in this proposal. The TDT tests for linkage between marker and disease loci, and was developed to analyse data from presently or recently stratified populations. (ii) To continue research on the very difficult theory of ascertainment sampling where the data were collected by an ascertainment procedure on one variable (e.g. blood pressure) but the analysis considers a second, correlated, variable- (e.g. serum cholesterol level). (iii) To continue research, using computer simulations,. on the statistical properties of genome mapping using anchored clones, especially in cases where complexities such as hotspots make 'an analytical approach very difficult. (iv) To initiate research on statistical tests for comparing two or more populations-with respect to genetical characteristics (for example to compare the heterozygosity of two populations using restriction endonuclease data). (v) To initiate research on the question of assessing, when several loci contribute towards a disease, how much of the total (genetic) contribution is accounted for by each locus, and what the inactive effects between the loci on their contributions are.
