About the Project
Most characters of any living organism are polygenically controlled and environmentally modified, including those threatening human health and those important in breeding for high yield, better quality and improved adaption of animals, plants and microbes. Understanding the molecular mechanisms underlying polygenic variation has been one of the most challenging areas both in the history of genetics and the era of modern functional genomics. The genome-wide marker assisted mapping of quantitative trait loci (QTL) has greatly opened the window of quantitative genetic analysis at the genome level. However, dissecting QTL to a genic level is still a task with exceptionally few successes due to the bottleneck in both mapping precision and resolution for the current linkage and linkage disequilibrium based QTL mapping strategies.
To address this fundamental challenge, this project is designed to develop novel theoretical and experimental strategies to unveil the molecular basis underpinning quantitative genetic variation at genic, transcriptional and their interactional levels. To achieve this, novel theoretical frameworks and analytical tools will be developed that enable integration of genome and transcriptome sequence data from segregating populations created from recurrent bi-directional selection and backcrossing (RSB) schemes. Feasibility, reliability and utility of the theoretical analyses and experimental strategies will be tested by experimentally exploring ethanol tolerance of budding yeast as an experimental model of quantitative traits. We established this yeast model for several major reasons. Firstly, we have many years of successful working experience in quantitative genetic analysis under a yeast model. It is a simple but effective working model to test some sophisticated fundamental questions in polygenic genetics. Ethanol tolerance has a significant value to industries and is one of central questions of yeast evolution. In this way, the project will open a new route for understanding the complex molecular basis of quantitative traits in crops and other plant/animal species.
This project will provide training in the key areas of genomics, molecular biology, statistical analysis and computer programing.
References
Lindsey J. Leach, Lin Wang, Michael J. Kearsey and Zewei Luo (2010). A multilocus tetrasomic linkage analysis using hidden Markov chain model. Proceedings of National Academy of Sciences USA [Pub ahead print].
Wang MH, XH Hu, G Li, Lindsey J Leach, E Potokina, A Druka, R. Waugh, M J Kearsey and ZW Luo (2009) Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data. PLoS Computational Biology 5(3) e1000317.
Chenqi Lu, Xiaohua Hu, Guiying Wang, L. J. Leach, Shengjie Yang, M. J. Kearsey and Z.W. Luo (2010) Why do essential proteins tend to be clustered in the yeast interactome network? Molecular BioSystems DOI: 10.1039
Wang GY, Lu CQ, Zhang RM, Hu XH and Luo ZW (2008) The E-cadherin gene polymorphism -160 CA and Cancer Risk: A Meta-Analysis of Twenty-Six Case-Control Studies. Am J Epidemiol. 167: 7-14.
Potokina E, Druka A, Luo ZW, Wise R, Waugh R and Kearsey M. (2008) Gene expression quantitative trait locus analysis of 16,000 barley genes reveals a complex pattern of genome wide transcriptional regulation. Plant Journal 53: 90-101.
Hu XH, MH Wang, T Tan, JR Li, H Yang, L Leach, RM Zhang and ZW Luo (2007). Genetic dissection of ethanol tolerance in budding yeast S. cerevisiae. Genetics 175: 1479-88.
Leach LJ, Z Zhang, CQ Lu, MJ Kearsey and ZW Luo (2007). The Role of Cis-Regulatory Motifs and Genetical Control of Expression in the Divergence of Yeast Duplicate Genes. Molecular Biology and Evolution 24: 2556-65.
Lu CQ, Z Zhang, LJ Leach, MJ Kearsey and ZW Luo (2007). Impacts of Yeast Metabolic Network Structure on Enzyme Evolution. Genome Biology 8: 407.
Luo ZW, E Potokina, A Druka, R Wise, R Waugh and MJ Kearsey (2007) SFP Genotyping from Affymetrix arrays is robust but largely detects cis-acting expression regulators. Genetics 176: 789–800.
Luo ZW, Zhang Z, Leach L, Zhang RM, Bradshaw JE, Kearsey MJ. (2006). Constructing genetic linkage maps under a tetrasomic model. Genetics 172: 2635-2645.
Zhang HT, XF Chen, MH Wang, JC Wang, QY Qi, RM Zhang, WQ Xu, QY Fei, QQ Cheng, F Chen, CS Zhu, SH Tao and ZW Luo (2004). Defective expression of TGF?RII is associated with CpG methylated promoter in primary non-small cell lung cancer. Clinical Cancer Research 10: 2359-67.
Luo ZW, RM Zhang and MJ Kearsey (2004). Theoretical basis for genetic linkage analysis in autotetraploid species. Proc. Natl. Acad. Sci. USA 101: 7040-45.
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