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   |  | The next few slides
   provide a short introduction to mapping the loci that are responsible for
   variation in a trait such as App expression level. These modulatory regions
   of the genome are sometimes called quantitative trait loci or QTLs. You may
   want to do some independent reading on this topic if this is your first
   exposure to QTL analysis. 
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   |  | The genetic reference
   population (GRP) of BXD recombinant inbred strains were originally generated
   about 25 years ago by Benjamin Taylor at The Jackson Laboratory. He crossed
   female C57BL/6J mice with male DBA/2J mice to generate the F1 and F2
   progeny. At the bottom of this slide we have schematized one chromosome pair
   from three of the BXD RI strains. 
   The dashed vertical lines that lead to the final BXD RI lines involve
   21 full sib matings (about 7 years of breeding). Some lines die out during
   inbreeding. For example, there is no longer any BXD3 strain. 
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   |  | Notes: 
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   |  | 1. Over the last decade,
   our group (Lu Lu and Rob Williams) and Jeremy Peirce and Lee Silver at
   Princeton have enlarged Ben TaylorÕs set. There are now just over 80 BXD
   strains. They have all been genotyped using about 13,700 markers (SNPs and
   microsatellites). These markers are used to define the ÒblueÓ and ÒredÓ
   regions of the chromosomes as shown in the figure above. 
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   |  | 2. Chromosomes of RI GRPs
   usually have about 4 times as many recombinations as those of F2 animals.
   However, unlike an F2, both chromosomes of an RI are identical. Therefore,
   50 RI strains contain as many recombinations as 100 F2 animals. 
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   |  | 3. BXD43 through BXD100
   were generated using a special method that resulted in a further doubling of
   the average recombination density per chromosome. The entire set of 80 BXDs
   therefore contains as many recombinations as about 260 F2 animals. 
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