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content="Jun-19-03: Requirement: The gene must be polymorphic to be genetically ÒupstreamÓ">
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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 ÒupstreamÓ</i></span><span style='font-size:82%;mso-special-format:
lastCR;display:none'><br>
</span></span></div>
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<div class=T style='mso-line-spacing:" 0 ";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>
</span></div>
</div>
<img border=0 src="slide0027_image108.gif" style='position:absolute;top:33.92%;
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<div style='position:absolute;top:0%;left:0%;width:84.02%;height:32.5%'><span
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>
</div>
<div id=NotesObj style='display:none'>
<table style='color:white' border=0 width="100%">
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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>
</td>
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<tr>
<td colspan=1></td>
<td align=left colspan=1><br>
</td>
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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>
</td>
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<td colspan=1></td>
<td align=left colspan=1><br>
</td>
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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>
</tr>
<tr>
<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>
</tr>
<tr>
<td colspan=1></td>
<td align=left colspan=1><br>
</td>
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<td colspan=1></td>
<td align=left colspan=1><font face=Verdana size=3>LetÕs 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"> </span>correlation with D2Mit423 as shown in the slide above.</font><br>
</td>
</tr>
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<td colspan=1></td>
<td align=left colspan=1><br>
</td>
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<td colspan=1></td>
<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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