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<div class=T style='mso-line-spacing:" 0 &#1;";position:absolute;top:7.47%;
left:1.22%;width:98.77%;height:85.04%'><span style='position:absolute;
top:0%;left:0%;width:100.0%'><span style='font-size:82%'><i>Requirement: The
gene must be polymorphic to </i></span></span><span style='position:absolute;
top:51.64%;left:3.7%;width:79.72%'><span style='font-size:82%'><i>be
genetically �upstream�</i></span><span style='font-size:82%;mso-special-format:
lastCR;display:none'><br>
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<div class=T style='mso-line-spacing:" 0 &#1;";position:absolute;top:32.94%;
left:1.56%;width:98.43%;height:40.0%'><span style='font-size:64%'><i>What are
targets of the Hars2 polymorphisms?</i></span><span style='font-size:82%;
mso-special-format:lastCR;display:none'><br>
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style='font-family:"Gill Sans";font-size:267%;color:#E9EB5D'><i>App and many
other<br>
</i></span></div>

<span style='position:absolute;top:33.33%;left:0%;width:100.0%'><span
style='font-family:"Gill Sans";font-size:267%;color:#E9EB5D'><i>correlated
transcripts and </i></span></span><span style='position:absolute;top:67.5%;
left:0%;width:84.02%'><span style='font-family:"Gill Sans";font-size:267%;
color:#E9EB5D'><i>other traits.</i></span></span></div>

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  <td align=left colspan=1><font face=Verdana size=3>Genes must be polymorphic
  to generate downstream genetic effects (as opposed to downstream molecular
  effects). Hars2 meets this condition because we have already mapped a
  functional polymorphism in the gene. We can therefore posit that Hars2 is a
  QT gene. What transcripts are downstream? <i>App</i> is one obvious
  candidate, but there are many more.</font><br>
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  <td align=left colspan=1><font face=Verdana size=3>The are several ways to
  look for downstream targets. The best and most obvious is to look up all
  transcripts that have high correlations with Hars2 itself. You should know
  how to do this. An alternative method is shown here for teaching purpose and
  to show you what to do if your gene of interest is not in our database. You
  need to know:</font><br>
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  <td align=left colspan=1><font face=Times size=3>1.</font><font face=Verdana
  size=3> Where your gene is located. You need this information to find a
  surrogate marker; a marker that is located very close to your gene of
  interest.</font><br>
  </td>
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  <td colspan=1></td>
  <td align=left colspan=1><font face=Verdana size=3>2. That your gene is
  polymorphic between C57BL/6J and DBA/2J.</font><br>
  </td>
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  <td align=left colspan=1><font face=Verdana size=3>Let�s look at the
  correlation of Hars2 with BXD genotypes as shown in the slide above to
  illustrate how to use markers as surrogate traits.</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=1></td>
  <td align=left colspan=1><font face=Verdana size=3>Go to the Trait Date and
  Editing window one more time. We want the data for Hars2 this time, not App.
  You should be able to show that Hars2 has a high<span style="mso-spacerun:
  yes">&nbsp; </span>correlation with D2Mit423 as shown in the slide above.</font><br>
  </td>
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  </td>
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  <td align=left colspan=1><font face=Verdana size=3>By clicking on the symbol
  D2Mit423 in the Correlation window, you will generate a new Trait Data window
  shown on the next slide.</font><br>
  </td>
 </tr>
</table>

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