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Final Comments

We have seen how to carry out a genome scan using interval mapping, assuming either a normal model or using a more robust procedure, and how to test the significance of peaks in the Z or LOD plot. What is left to do? Unfortunately, quite a lot. As explained at the beginning of the week, most QT differences (and the same probably applies to qualitative traits) will require differences at a number of loci to explain them, and interval mapping is clearly a one locus at a time approach. A modification has been given to permit the inclusion of effects due to differences at specified loci, while searching for others, but this is still far from a general attack on the problem. The truth is that there are not, as yet any satisfactory multilocus scanning procedures in use.

Many ideas exist, and here is one that was explored by Karl Broman in his Berkeley PhD thesis. Firstly, forget interval mapping. It requires too much computation to be feasible for 3, 4 or more loci. And besides, as Karl and others have shown, its advantages in locating QTL with current marker densities and sample sizes, are small, in comparison with methods focussing solely on the analysis at the markers. Forget testing, because finding QTL is not a testing problem: the loci are there, and the problem is finding them, and their mode of action. Karl viewed the problem as one of model selection, and the task as finding ways of searching through the huge number of multilocus models, and comparing them in their ability to explain the associations between marker data and phenotype. Work along these lines has barely begun, and it is far from clear whether it is likely to be successful. In my view, much more attention needs to be paid to information in data concerning the QT in the parental lines and the progeny, as we seek clues to reduce the number of possible models to a realistic number through which we can search.



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Next: About this document Up: Stat 260: Statistics Previous: Deciding upon significance



Simon Cawley
Mon Apr 20 19:59:26 PDT 1998