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<title>PowerPoint Presentation  -  Complex trait analysis, develop-ment, and
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   <td colspan=1></td>
   <td align=left colspan=1><font face=Verdana size=3>An even higher blow-up of
   part of the Chr 7 physical map of variation in App expression in brain.<span
   style="mso-spacerun: yes">&nbsp; </span>The QTL region actually extends from
   about 119 to 129.</font><br>
   </td>
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   <td align=left colspan=1><font face="Times New Roman" size=4>Notes:</font><br>
   </td>
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   <td colspan=1></td>
   <td align=left colspan=1><font face="Times New Roman" size=4>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.</font><br>
   </td>
  </tr>
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   <td colspan=1></td>
   <td align=left colspan=1><font face="Times New Roman" size=4>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?</font><br>
   </td>
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   <td colspan=1></td>
   <td align=left colspan=1><font face=Verdana size=3>2.<span
   style="mso-spacerun: yes">&nbsp; </span>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).</font><br>
   </td>
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   <td colspan=1></td>
   <td align=left colspan=1><font face=Verdana size=3>3.<span
   style="mso-spacerun: yes">&nbsp; </span>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.</font><br>
   </td>
  </tr>
  <tr>
   <td colspan=1></td>
   <td align=left colspan=1><font face=Verdana size=3>4.<span
   style="mso-spacerun: yes">&nbsp; </span>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.</font><br>
   </td>
  </tr>
  <tr>
   <td colspan=1></td>
   <td align=left colspan=1><font face=Verdana size=3>5.<span
   style="mso-spacerun: yes">&nbsp; </span>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.</font><br>
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