Conclusions about QTL Mapping

See - Statistical Genomics: Linkage, Mapping, and QTL Analysis. pg 377, 381, 385, 394, 401, 444.

"QTL mapping is a combination of qualitative linkage analysis and quantitative genetic analysis." pg 381.

"QTL mapping is based on the association between the trait values and the marker genotypes." pg 385

"When several loci are considered in an analysis, missing genotypic combinations cannot be avoided and it may not be apparent that there is missing data even when the data sheets are complete. This is hidden missing data." pg 387

"Using biological knowledge and linkage analysis, we can determine the mode of the marker inheritance and their genomic locations. Now the question becomes whether or not we use that large amount of linkage information to infer the genetics of quantitative traits. The underlying genetic assumptions for finding the relationships between quantitative trait inheritance and the genetic markers are:

1. Genes controlling the quantitative traits can be mapped on the genome like simple genetic markers.
2. If the markers cover a large portion of the genome, then there is a good chance that some of the genes controlling quantitative traits will be linked to some of the genetic markers.
3. If the genes and the markers are segregating in a genetically defined population, then the linkage relationships among them may be discoverable by looking at the association between trait variation and the marker segregation pattern."
   
   "Certainly, if the genotypes of the genes controlling the [quantitative] traits can be scored, then the problem becomes one of simple linkage analysis. In practice, the genotypes of the genes cannot be observed; instead what we can actually observe are the continuous trait values." pg. 388

"The disadvantage of single-marker analysis are:

1. The putative QTL genotypic means and QTL positions are confounded. The confounding causes the estimator of QTL effects to be biased and the statistical power to be low, particularly when linkage map density is low.
2. QTL positions cannot be precisely determined, due to the non-independence among the hypothesis tests for linked markers that confound QTL effect and position." pg. 389

"The QTL is determined to be located near a marker if phenotypic values for the trait are significantly different among the marker genotypes. A common mistake is to treat each of the lod score peaks as genome location corresponding to a different QTL. The peaks of the lod curve may not be the results of QTL's under the peaks." pg. 401

Because QTL effect and position are confounded for single marker analysis: Several QTL's located near the marker would cause the peak to be an inaccurate estimate of QTL position.

The best method of identifying QTL position is to use interval mapping. Interval mapping uses flanking markers with the QTL located between two markers. Even with interval mapping, the peak lod score may not represent the QTL position, due to multiple QTL's within the interval. The lod peak is the QTL position only when there is a single QTL. pg. 401