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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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