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visibility:hidden'><img src="master03_background.gif" v:shapes="_x0000_s1026"
style='position:absolute;top:0%;left:0%;width:100.0%;height:100.0%'><img
border=0 src="slide0017_image074.gif" style='position:absolute;top:40.45%;
left:73.24%;width:14.56%;height:5.3%'>
<div class=O style='position:absolute;top:40.81%;left:74.56%;width:11.92%;
height:7.24%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:60.97%'><span
style='font-family:Gadget;font-size:150%;color:white'>aa<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:41.46%;left:0%;width:100.0%;height:60.97%'><span
style='font-family:Gadget;font-size:150%;color:white;mso-special-format:lastCR;
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</span></div>
</div>
<img border=0 src="slide0017_image075.gif" style='position:absolute;top:16.6%;
left:73.24%;width:14.56%;height:5.3%'>
<div class=O style='position:absolute;top:16.96%;left:74.56%;width:11.92%;
height:7.24%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:60.97%'><span
style='font-family:Gadget;font-size:150%;color:white'>aaaa<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:41.46%;left:0%;width:100.0%;height:60.97%'><span
style='font-family:Gadget;font-size:150%;color:white;mso-special-format:lastCR;
display:none'><br>
</span></div>
</div>
<div style='position:absolute;top:20.31%;left:71.65%;width:25.96%;height:19.78%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:9.82%;left:5.1%;width:95.4%;
height:83.03%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:45.16%'><span
style='font-size:267%;color:#E2EBF0'>D2 strain</span><span style='font-family:
Palatino;font-size:333%;color:#FBFDB8;display:none'><br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:49.46%;left:0%;width:88.77%;height:50.53%'><span
style='font-family:Palatino;font-size:333%;color:#FBFDB8;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:43.81%;left:71.65%;width:25.56%;height:19.78%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.71%;left:5.18%;width:94.81%;
height:83.03%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:45.16%'><span
style='font-size:267%;color:#F6BF69'>B6 strain</span><span style='font-family:
Palatino;font-size:333%;color:#F6BF69;display:none'><br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:48.38%;left:0%;width:87.43%;height:50.53%'><span
style='font-family:Palatino;font-size:333%;color:#F6BF69;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
</div>
<img border=0 src="slide0017_image076.gif" style='position:absolute;top:17.31%;
left:31.25%;width:1.32%;height:42.22%'><img border=0
src="slide0017_image077.gif" style='position:absolute;top:40.63%;left:31.39%;
width:39.86%;height:3.53%'>
<div style='position:absolute;top:17.13%;left:40.0%;width:30.59%;height:31.44%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:11.23%;left:4.32%;width:90.9%;
height:83.7%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:61.74%'><span
style='position:absolute;top:0%;left:0%;width:100.0%'><span style='font-size:
233%;color:#E9EB5D'><i>amount of </i></span></span><span style='position:absolute;
top:59.78%;left:0%;width:100.0%'><span style='font-size:233%;color:#E9EB5D'><i>transcript</i></span><span
style='font-family:Palatino;font-size:367%;color:#E9EB5D;display:none'><br>
</span></span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:65.77%;left:0%;width:100.0%;height:34.89%'><span
style='font-family:Palatino;font-size:367%;color:#E9EB5D;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:6.0%;left:72.45%;width:21.32%;height:19.78%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:9.82%;left:6.21%;width:87.57%;
height:83.03%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:45.16%'><span
style='font-size:267%;color:white'>4 </span><span style='font-size:233%;
color:white'>units</span><span style='font-family:Palatino;font-size:333%;
color:#E9EB5D;display:none'><br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:49.46%;left:0%;width:100.0%;height:50.53%'><span
style='font-family:Palatino;font-size:333%;color:#E9EB5D;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:29.5%;left:72.45%;width:21.32%;height:19.78%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.71%;left:6.21%;width:87.57%;
height:83.03%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:45.16%'><span
style='font-size:267%;color:white'>2</span><span style='font-size:233%;
color:white'> units</span><span style='font-family:Palatino;font-size:333%;
color:#E9EB5D;display:none'><br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:48.38%;left:0%;width:100.0%;height:50.53%'><span
style='font-family:Palatino;font-size:333%;color:#E9EB5D;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
</div>
<img border=0 src="slide0017_image078.gif" style='position:absolute;top:15.72%;
left:31.25%;width:40.26%;height:5.47%'>
<div class=O style='position:absolute;top:17.84%;left:9.93%;width:4.76%;
height:16.43%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0'>D<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:49.46%;left:0%;width:83.33%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
<div class=O style='position:absolute;top:17.84%;left:17.88%;width:4.23%;
height:16.43%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#F6BF69'>B<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:49.46%;left:0%;width:84.37%;height:50.53%'><span
style='font-size:300%;color:#F6BF69;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
<div style='position:absolute;top:77.73%;left:5.43%;width:104.37%;height:26.32%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:8.72%;left:1.26%;width:98.73%;
height:87.24%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:62.3%'><span
style='position:absolute;top:0%;left:0%;width:100.0%'><span style='font-size:
233%;color:#E2EBF0'>D</span><span style='font-size:233%;color:#E9EB5D'> </span><span
style='font-size:200%;color:#E9EB5D'>and </span><span style='font-size:233%;
color:#F6BF69'>B</span><span style='font-size:233%;color:#E9EB5D'> </span><span
style='font-size:200%;color:#E9EB5D'>may be SNP-like variants in the promoter </span></span><span
style='position:absolute;top:61.72%;left:0%;width:97.55%'><span
style='font-size:200%;color:#E9EB5D'>itself (cis QTL) or in </span><span
style='font-size:200%;color:#EAEC5E'>upstream genes (trans QTLs)</span><span
style='font-size:300%;color:#E9EB5D;display:none'><br>
</span></span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:63.84%;left:0%;width:86.88%;height:36.15%'><span
style='font-size:300%;color:#E9EB5D;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
</div>
<div class=O style='position:absolute;top:7.59%;left:4.23%;width:22.78%;
height:16.25%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:1.74%;width:97.09%;
height:33.69%'><span style='font-size:200%;color:#E9EB5D'>UPSTREAM<br>
</span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:32.6%;left:0%;width:100.0%;
height:33.69%'><span style='font-size:200%;color:#E9EB5D'>modulators<br>
</span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:66.3%;left:4.65%;width:90.69%;
height:33.69%'><span style='font-size:200%;color:#E9EB5D;mso-special-format:
lastCR;display:none'><br>
</span></div>
</div>
<div style='position:absolute;top:7.59%;left:44.5%;width:17.21%;height:18.19%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:3.88%;left:6.92%;width:83.84%;
height:90.29%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0'>High<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:49.46%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:63.78%;left:8.74%;width:6.62%;height:18.19%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:3.88%;left:20.0%;width:72.0%;
height:90.29%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0'>D<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:49.46%;left:0%;width:83.33%;height:50.53%'><span
style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:63.78%;left:15.09%;width:6.22%;height:18.19%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:3.88%;left:19.14%;width:68.08%;
height:90.29%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:50.53%'><span
style='font-size:300%;color:#F6BF69'>B<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:49.46%;left:0%;width:84.37%;height:50.53%'><span
style='font-size:300%;color:#F6BF69;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
</div>
<div style='position:absolute;top:71.02%;left:7.54%;width:16.02%;height:12.72%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:5.55%;left:7.43%;width:91.73%;
height:86.11%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:50.0%'><span
style='font-size:200%;color:#E9EB5D'><i>cis QTL</i></span><span
style='font-size:200%;color:#E9EB5D;display:none'><br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:48.38%;left:0%;width:82.88%;height:50.0%'><span
style='font-size:200%;color:#E9EB5D;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
</div>
<img border=0 src="slide0017_image079.gif" style='position:absolute;top:57.24%;
left:-1.05%;width:101.98%;height:7.59%'>
<div class=O style='position:absolute;top:44.16%;left:47.15%;width:9.4%;
height:12.72%'>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:0%;left:0%;width:100.0%;height:51.38%'><span
style='font-size:233%;color:#F6BF69'>Low<br>
</span></div>
<div style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:50.0%;left:0%;width:83.09%;height:51.38%'><span
style='font-size:233%;color:#F6BF69;mso-special-format:lastCR;display:none'><br>
</span></div>
</div>
<div style='position:absolute;top:58.12%;left:.79%;width:114.56%;height:6.53%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='mso-line-spacing:" 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17;position:absolute;top:10.81%;left:1.15%;width:98.84%;height:72.97%'><span
style='font-family:Gadget;font-size:167%;color:white'>>>>>PROMOTER--ATG-Exon1-Intron1-Exon2-Intron2
- etc-3'UTR >>>>></span></div>
</div>
<img border=0 src="slide0017_image080.gif" style='position:absolute;top:37.98%;
left:8.6%;width:13.77%;height:20.67%'>
<div class=O style='position:absolute;top:39.75%;left:10.06%;width:3.57%;
height:12.01%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white'><b><br>
</b></span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:52.94%;left:7.4%;width:85.18%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
mso-special-format:lastCR;display:none'><b><br>
</b></span></div>
</div>
<div class=O style='position:absolute;top:40.1%;left:17.48%;width:3.57%;
height:12.01%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white'><b><br>
</b></span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:51.47%;left:7.4%;width:85.18%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
mso-special-format:lastCR;display:none'><b><br>
</b></span></div>
</div>
<img border=0 src="slide0017_image081.gif" style='position:absolute;top:33.74%;
left:8.6%;width:13.77%;height:20.67%'>
<div class=O style='position:absolute;top:35.86%;left:17.48%;width:3.57%;
height:12.01%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white'><b><br>
</b></span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:51.47%;left:7.4%;width:85.18%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
mso-special-format:lastCR;display:none'><b><br>
</b></span></div>
</div>
<div class=O style='position:absolute;top:35.51%;left:10.06%;width:3.57%;
height:12.01%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white'><b><br>
</b></span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:51.47%;left:7.4%;width:85.18%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
mso-special-format:lastCR;display:none'><b><br>
</b></span></div>
</div>
<div class=O style='position:absolute;top:37.8%;left:20.66%;width:.13%;
height:12.01%'>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
display:none'><b><br>
</b></span></div>
<div style='text-align:center;mso-line-spacing:" 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:51.47%;left:0%;width:100.0%;
height:48.52%'><span style='font-family:Palatino;font-size:233%;color:white;
mso-special-format:lastCR;display:none'><b><br>
</b></span></div>
</div>
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17;position:absolute;top:0%;left:0%;width:100.0%;height:50.0%'><span
style='font-size:200%;color:#E9EB5D'><i>trans QTL</i></span><span
style='font-size:200%;color:#E9EB5D;display:none'><br>
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<td align=left colspan=1><font face=Helvetica size=3>This slide is
illustrates two categories of QTLs that modulate variability in transcript
abundance.</font><br>
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<td align=left colspan=1><font face=Helvetica size=3>1. cis QTLs are defined
as QTLs that are closely linked to the gene whose transcript is the measured
trait. For example, a polymorphism in the promoter that affects the binding
of a transcription factor. However, cis QTLs can be far upstream or downstream
polymorphisms in enhancers. They may also be polymorphisms in neigghboring
genes.</font><br>
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<td align=left colspan=1><font face=Helvetica size=3>2. trans QTLs map far
enough away from the location of the gene that gives rise to the transcript
that is being measured so that we can be quite certain that the QTL is not IN
the gene itself. The most blatant type of trans-QTL would be a polymorphism
in a transcription factor. BUT in the majority of cases, the trans QTLs can
be far removed in a mechanistic sense from the actual events modulating
transcript abundance. That is why there are three overlappoing arrows above.<span
style="mso-spacerun: yes"> </span>The way in which an upstream
polymorphism influences a downstream difference in mRNA abundance can be very
indirect. Effects can :</font><br>
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<td align=left colspan=1><font face=Helvetica size=3><span
style="mso-spacerun: yes"> </span>a.<span style="mso-spacerun:
yes"> </span>cross tissue types (a polymorphic liver enzyme may affect
CNS gene expression)</font><br>
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<td align=left colspan=1><font face=Helvetica size=3><span
style="mso-spacerun: yes"> </span>b.<span style="mso-spacerun:
yes"> </span>cross time (the modulator is only expressed for one day
during development but has permanent effects in adults),</font><br>
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<td align=left colspan=1><font face=Helvetica size=3><span
style="mso-spacerun: yes"> </span>c.<span style="mso-spacerun:
yes"> </span>may be contingent on environmental factors (heat shock may
trigger the expression of a polymorphic factor that affects mRNA abundance).</font><br>
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