Molecular-Genetics of Variation for Complex Traits The genes controlling most single-gene disorders of humans will be molecularly cloned and characterized within the near future. The remaining and more difficult challenge will be to molecularly characterize genes controlling diseases with complex inheritance. In the face of this challenge, there is the daunting recognition that very little is known about the molecular-genetic basis of variation for complex traits in general. Although research over the past decade has been remarkably successful in describing variation for complex traits in statistical terms, we know very little about the underlying variation in gene function/expression that is its proximal cause. This is not only true for human diseases, but even for complex traits in model organisms such as Drosophila, mouse and maize that offer powerful genetic tools for the dissection of complexity. The proposed research seeks to uncover the molecular-genetic basis for variation in complex traits using maize and its relatives (the teosintes) is the model system. Two traits will be investigated. (1) Plant architecture in maize is controlled in part by teosinte branched 1 (tb1). tb1 has been cloned and is known to control differences in plant architecture between maize and teosinte. The proposed research will examine naturally occurring allelic variation at tb1 and employ intragenic recombination mapping to localize phenotypic effects to specific regions of the gene. Variation in gene expression among natural alleles will be characterize at the cell, tissue and organ levels. (2) Trichome (epidermal hairs) formation in teosinte is controlled by a small number of quantitative trait loci (QTL) for which candidate genes are known. Alleles of these QTL from natural populations will be incorporated into a common isogenic background and characterized. Mutagenesis will be used to assay whether the candidate genes function in trichome formation, and gene expression will be assayed to determine if the candidate genes are specifically expressed in trichome cells. The long-term goal of this research is to understand how variation at the molecular level in gene expression/function produces variation for complex traits in natural populations.
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