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<div id=SlideObj class=sld style='position:absolute;top:0px;left:0px;
width:755px;height:566px;font-size:16px;background-color:#484848;clip:rect(0%, 101%, 101%, 0%);
visibility:hidden'><img src="master03_background.png" v:shapes="_x0000_s1026"
style='position:absolute;top:0%;left:0%;width:100.0%;height:100.0%'><img
border=0 src="slide0003_image054.png" 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:"-126 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:"-126 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>
<img border=0 src="slide0003_image055.png" 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:"-126 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:"-126 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:19.43%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.0%;left:5.1%;width:95.4%;
height:84.54%'>
<div style='mso-line-spacing:"-384 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:"-384 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:19.43%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.9%;left:5.18%;width:94.81%;
height:84.54%'>
<div style='mso-line-spacing:"-384 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:"-384 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="slide0003_image056.png" style='position:absolute;top:17.31%;
left:31.25%;width:1.32%;height:42.22%'><img border=0
src="slide0003_image057.png" style='position:absolute;top:40.63%;left:31.39%;
width:39.86%;height:3.53%'>
<div style='position:absolute;top:20.67%;left:38.27%;width:30.19%;height:26.32%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:6.04%;left:4.38%;width:92.1%;
height:89.93%'>
<div style='mso-line-spacing:"-320 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:0%;left:0%;width:100.0%;height:58.2%'><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:53.84%;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:"-422 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16;position:absolute;top:61.19%;left:0%;width:100.0%;height:38.8%'><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:21.05%;height:19.43%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.0%;left:6.28%;width:88.67%;
height:84.54%'>
<div style='mso-line-spacing:"-384 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:"-384 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:21.05%;height:19.43%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:10.9%;left:6.28%;width:88.67%;
height:84.54%'>
<div style='mso-line-spacing:"-384 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:"-384 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="slide0003_image058.png" 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:"-350 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:"-350 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:"-350 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:"-350 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:79.5%;left:5.43%;width:104.1%;height:13.6%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='mso-line-spacing:"-256 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:3.89%;left:1.27%;width:98.72%;
height:93.5%'><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:34.72%;left:0%;width:99.74%'><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'>.</span></span></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:"-233 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:"-233 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:"-233 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:16.95%;height:17.84%;
filter:DropShadow(Color=#000000, OffX=2, OffY=2)'>
<div class=O style='position:absolute;top:3.96%;left:7.03%;width:85.15%;
height:92.07%'>
<div style='mso-line-spacing:"-350 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:"-350 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:6.35%;height:17.84%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:3.96%;left:20.83%;width:75.0%;
height:92.07%'>
<div style='mso-line-spacing:"-350 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:"-350 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:5.96%;height:17.84%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:3.96%;left:20.0%;width:71.11%;
height:92.07%'>
<div style='mso-line-spacing:"-350 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:"-350 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:12.54%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='position:absolute;top:5.63%;left:7.43%;width:91.73%;
height:87.32%'>
<div style='mso-line-spacing:"-233 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:"-233 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="slide0003_image059.png" 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:"-272 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:"-272 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:113.37%;height:6.36%;
filter:DropShadow(Color=#000000, OffX=1, OffY=1)'>
<div class=O style='mso-line-spacing:"-200 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;position:absolute;top:11.11%;left:1.16%;width:98.83%;
height:75.0%'><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="slide0003_image060.png" style='position:absolute;top:37.98%;
left:8.6%;width:13.77%;height:20.67%'>
<div class=O style='position:absolute;top:40.28%;left:10.99%;width:1.72%;
height:11.48%'>
<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:46.15%'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b></b></span><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:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:50.76%;left:7.69%;width:84.61%;
height:50.76%'><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:40.63%;left:18.41%;width:1.72%;
height:11.48%'>
<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:46.15%'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b></b></span><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:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:49.23%;left:7.69%;width:84.61%;
height:50.76%'><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="slide0003_image061.png" style='position:absolute;top:33.74%;
left:8.6%;width:13.77%;height:20.67%'>
<div class=O style='position:absolute;top:36.39%;left:18.41%;width:1.72%;
height:11.48%'>
<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:46.15%'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b></b></span><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:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:49.23%;left:7.69%;width:84.61%;
height:50.76%'><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:36.04%;left:10.99%;width:1.72%;
height:11.48%'>
<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
height:46.15%'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b></b></span><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:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:49.23%;left:7.69%;width:84.61%;
height:50.76%'><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:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17;position:absolute;top:0%;left:0%;width:100.0%;
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style='font-size:200%;color:#E9EB5D'><i>trans QTL</i></span><span
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<td align=left colspan=1><font face=Helvetica size=3>This slide is
illustrates two major types of QTLs that modulate variability in
transcript-relative steady state 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 binding of a
transcription factor. However, cis QTLs can be far upstream or downstream polymorphisms
in enhancers or may be in 3� UTR binding sites that affect message stability.</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 fairly 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 overlapping
arrows in the figure.<span style="mso-spacerun: yes"> </span>The way in
which an upstream polymorphism influences a downstream difference in mRNA
abundance can be 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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