[分子数量遗传学课件]leture8 Interval mapping.pptVIP

Interval mapping outline Model ML and EM algorithm LR test Haley-Knott regression approximation Examples Advantages and disadvantages Suggested reading Lander, E.S. and D. Botstein.1989. Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185-199. Haley, C.S. and S.A. Knott. 1992. A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69:315-324 Churchill, G.A. and R.W. Doerge. 1994. Empirical threshold values for quantitative trait mapping. Genetics 138:963-971. Visscher, P.M., R. Thompson and C.S. Haley. Confidence intervals in QTL mapping by bootstrapping. Genetics 143:1013-1020 Single versus multiple markers Single marker not possible to distinguish between size of a QTL effect and its position (relative to the marker). less power if the markers are far apart Multiple markers there is more power in detecting a QTL, recombination rate between QTL and markers (i.e. position of QTL) is possible. QTL detection with markers BC design F2 design two marker loci – F2 design Gamete probabilities with two markers Marginal probability Giving expected frequencies in the F2 of M1M1M2M2 offspring as Pr(M1QM2/M1QM2)=[(1-r1)(1-r2)/2]2 Pr(M1QM2/M1qM2)=2[(1-r1)(1-r2)/2](r1r2/2) Pr(M1qM2/M1qM2)=(r1r2/2)2 Two marker loci Maximum likelihood estimation The principle The Likelihood can be calculated for a given set of parameters (particularly QTL effect and QTL position) given the observed data on phenotypes and marker genotypes. The estimates for the parameters are those were the likelihood are highest. The significance can be tested with a likelihood ratio test Maximum likelihood Likelihood ratio test Interval mapping by regression Haley-Knott Regression (1992) ML estimator is rather computationaly demanding Resampling methods require thousands of ML estimates per experiment Haley-Knott regression Gives an approximation of ML interval mapping Easily computed ? Haley, C.S. and S.A. K