Quantitative Trait Loci.

Inbred lines are homozygous at all loci.  This includes visible marker genes, quantitative traits and molecular markers such as RFLP sites or microsatellite sites.

Consider two inbred lines which differ in some quantitative trait such that Inbred Line A has a very high phenotypic score and Inbred Line B has a very low phenotypic score.  By careful strain comparisons,  it has been established that the differences are genetic.  With QTL analysis it is possible to estimate the number of loci that differ between the inbred lines (Halls' Goal 2) for that quantitative trait and determine the approximate location of those genes (Hall's Goal 3).

The first step in QTL analysis is to define and measure the phenotype using the appropriate tools.  The more accurately the phenotype is measured, the better the chance of success.  This is especially important when studying behavior. 

A typical QTL analysis  starts by crossing two inbred lines or organisms to create an F₁ generation.  These inbred lines will have already been characterized for molecular markers at a resolution of 10 centimorgans or less. 

The F₁ generation is used to generate the segregating F₂ generation or either (or both) of the backcross generations.  For these generations,  several hundred  progeny are tested for the quantitative phenotype and simultaneously tested for hundreds of molecular markers.    From a practical point of view, backcrosses are much easier to analyze than F₂ progeny since backcross progeny have either the heterozygous genotype or one of two possible homozygous genotypes.   F₂ progeny can have all three genotypes.  

To detect QTLs, the phenotype scores for each animal are tested for association with each marker locus.  That is, the experimenter is trying to detect linkage between a microsatellite and the quantitative phenotype. 

 QTL detection depends on adequate statistical testing.   The power of the statistical test depends on the number of progeny genotyped, the effects of each QTL (strong effects are more easily detected than weak effects), the type of cross, and the dominance of the QTL.  

QTL detection is quite difficult.  Suspected QTL's must be replicated and any remaining associations have to be tested by further breeding analyses.  

Recombinant Inbreed Strains and QTL's"

Sometimes, recombinant inbred strains are used as a preliminary screen coupled with other mapping populations.  In theory, since a single genotype is represented by an inbred line it is possible to look at variation across a series of environments.  On the other hand, each RI line represents a single, rare homozygous genotype from the F₂ cross and it would be extremely rare to have enough RI lines to get significance.

Extension of QTL analyses:

The methodology is still being developed but it is possible to extend QTL analyses to outbred lines or selective bred populations.  Fine scale analyses might utilize half-sib and sib-pair populations.  Recently, new methods have been introduced to deal with dominance and with epistasis.