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:
- Genes controlling the quantitative traits can be mapped on the genome
like simple genetic markers.
- 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.
- 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:
- The putative QTL genotypic means and QTL positions ae 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.
- 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
