|  |  | 
 
  |  | An even higher blow-up of
  part of the Chr 7 physical map of variation in App expression in brain.  The QTL region actually extends from
  about 119 to 129. 
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  |  | 
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  |  | Notes: 
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  |  | 1. As mentioned
  in the previous slide another important approach to ranking candidates is
  based on the number of sequence variants that distinguish the parental
  strains. If we were sure that the sequences of the gene, its promoter, and
  its enhancers were identical between the strains then we could discount--but
  not eliminate--that gene as a candidate. The Gtf3c1 candidate almost falls
  into this category: of 663 known SNPs in and around this gene, only four
  differ between C57BL/6J and DBA/2J. Gtf3c1 is essentially
  identical-by-descent in these strains and is a less likely candidate. In
  contrast, if the two alleles of the gene have dozens of functional variants
  in exons, promoters, enhancers, and splice sites, then it becomes a higher
  priority candidate. 
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  |  | Of course it
  only takes a single critical sequence variant to generate downstream effects.
  The argument above is really about the prior probabilities. Where would you
  place your bets given the information at hand? 
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  |  | 2.  If you scroll down the INTERVAL
  ANALYST you will find that Ctbp2 is a particularly interesting candidate that
  contains lots of SNPs (n = 75 and a SNP density of 0.55 SNP/Kb). Ctbp2 is
  also closer to our QTL peak than was Gtf3c1. Not only does Ctbp2 contain lots
  of SNPs but it is also is associated with a powerful cis QTL with an LRS of
  24.2 (divide by 4.61 to get the equivalent LOD score of 5.25). 
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  |  | 3.  At this high magnification,
  individual genes are distinct. They are color coded by their density of SNPs.
  Bright orange represents those genes that have a high SNP density (C57BL/6J
  versus DBA/2J), black represents genes with low SNP density. Roll the cursor
  over a gene block and its name will pop up, along with information on exon
  number. 
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  |  | 4.  Beneath the physical map you will
  find an INTERVAL ANALYST table that lists information on known genes in the
  region on which you have zoomed the Physical Map. 
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  |  | 5.  As always: error-checking is
  important. Some genes may be missing from the Interval Analyst (recent
  additions or errors of omission). In this case the Zranb1 gene that is
  located just proximal to Ctbp2 is not listed in the INTERVAL ANALYST.
  Double-check the interval using the Genome Browser links (blue and beige
  horizontal bars) at the top of the PHYSICAL MAP. 
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