Methods for analyzing variation, selection and evolution of correlated characters will be developed and applied to different systems of interest to biologists.
Specific aims i nvolve the utilization of statistical associations (linkage disequilibria) between polymorphisms at molecular marker loci and other genes to solve problems in animal and plant breeding, human genetics, and evolution: (i) Augmenting the efficiency of artificial selection in the improvement of economically important characters of crop plants and domesticated animals. This will involve the derivation of optimal selection criteria (selection indices) incorporating information both from traditional phenotypic measurements and from the molecular marker loci that are statistically associated with important quantitative traits. Constraints on the efficiency of marker-assisted selection in long-term breeding programs will be analyzed mathematically and by computer simulation, including a time limit for the maximum response to selection, the size of the breeding population, the relative cost of obtaining molecular and phenotypic information, the influence of genetic dominance and epistasis, and the mating system of the population. (ii) Fine-scale mapping of particular genes, such as those causing human genetic diseases, and morphological difference or reproductive isolation between species. Methods that simultaneously employ information from multiple marker loci will be developed to overcome statistical limitations of previous methods that utilize linkage disequilibria with only one or two markers at a time. This should help to localize a particular gene of interest to a chromosomal region of less that one centimorgan, facilitating subsequent identification of the gene by DNA sequencing. (iii) Applications of genetics in conservation biology,. Associations and interactions among molecular marker loci, genes contributing to inbreeding depression (e.g. recessive lethal mutations) and quantitative trait loci will be analyzed for populations that have been gradually or suddenly reduced in numbers. Understanding situations in which molecular genetic polymorphism is not correlated with inbreeding depression or adaptive potential (risk of population extinction) will help to curtail the misuse of genetics in conservation biology.
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