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style='text-align:left'><span style='font-size:233%;color:#E9EB5D'><i>amount of
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style='text-align:left'><span style='font-size:233%;color:#E9EB5D'><i>transcript</i></span><span
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</layer></div>

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<div><script>
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<div style='mso-line-spacing:"-384 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16'><span style='font-size:267%;color:white'>4 </span><span style='font-size:
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color:#E9EB5D;display:none'><br>
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</span></div>

</layer></div>

</layer></div>

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<div><script>
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<div style='mso-line-spacing:"-384 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
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233%;color:white'> units</span><span style='font-family:Palatino;font-size:
333%;color:#E9EB5D;display:none'><br>
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<div style='mso-line-spacing:"-384 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16'><span style='font-family:Palatino;font-size:333%;color:#E9EB5D;mso-special-format:
lastCR;display:none'><br>
</span></div>

</layer></div>

</layer></div>

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<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
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<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
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<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

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<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
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</span></div>

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</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#F6BF69;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer><script>
	mytop = 0.79 * g_height; myleft = 0.05 * g_width; myheight = 0.13 * g_height; mywidth = 1.04 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.12 * g_height; mywidth = 1.02 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%;mso-line-spacing:"-256 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;mso-line-spacing:"-256 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.06 * g_height; mywidth = 1.02 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script><span
style='text-align:left'><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></layer><script>
	mytop = 0.04 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 1.02 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script><span
style='text-align:left'><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></layer></div>

</layer></div>

</layer><script>
	mytop = 0.07 * g_height; myleft = 0.04 * g_width; myheight = 0.16 * g_height; mywidth = 0.22 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.22 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-233 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-size:200%;color:#E9EB5D'>UPSTREAM<br>
</span></div>

</layer><script>
	mytop = 0.05 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.22 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-233 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-size:200%;color:#E9EB5D'>modulators<br>
</span></div>

</layer><script>
	mytop = 0.1 * g_height; myleft = 0.01 * g_width; myheight = 0.05 * g_height; mywidth = 0.2 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-233 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-size:200%;color:#E9EB5D;
mso-special-format:lastCR;display:none'><br>
</span></div>

</layer></div>

</layer><script>
	mytop = 0.07 * g_height; myleft = 0.44 * g_width; myheight = 0.17 * g_height; mywidth = 0.16 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.16 * g_height; mywidth = 0.14 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.14 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16'><span style='font-size:300%;color:#E2EBF0'>High<br>
</span></div>

</layer><script>
	mytop = 0.08 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.14 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:16;mso-text-indent-alt:
16'><span style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer></div>

</layer><script>
	mytop = 0.63 * g_height; myleft = 0.08 * g_width; myheight = 0.17 * g_height; mywidth = 0.06 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.16 * g_height; mywidth = 0.04 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.04 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#E2EBF0'>D<br>
</span></div>

</layer><script>
	mytop = 0.08 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.03 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#E2EBF0;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer></div>

</layer><script>
	mytop = 0.63 * g_height; myleft = 0.15 * g_width; myheight = 0.17 * g_height; mywidth = 0.05 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.16 * g_height; mywidth = 0.04 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.04 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#F6BF69'>B<br>
</span></div>

</layer><script>
	mytop = 0.08 * g_height; myleft = 0 * g_width; myheight = 0.08 * g_height; mywidth = 0.03 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-350 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:300%;color:#F6BF69;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer></div>

</layer><script>
	mytop = 0.71 * g_height; myleft = 0.07 * g_width; myheight = 0.12 * g_height; mywidth = 0.16 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.1 * g_height; mywidth = 0.14 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.14 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-233 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:200%;color:#E9EB5D'><i>cis QTL</i></span><span
style='font-size:200%;color:#E9EB5D;display:none'><br>
</span></div>

</layer><script>
	mytop = 0.05 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.12 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-233 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:200%;color:#E9EB5D;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer></div>

</layer><script>
	mytop = 0.57 * g_height; myleft = -0.01 * g_width; myheight = 0.07 * g_height; mywidth = 1.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script language=JavaScript><!--
xx = -0.01 * g_width;
yy = 0.57 * g_height;
ht = 0.07 * g_height;
wd = 1.01 * g_width;
document.write(
'<img border=0 src="slide0003_image059.png" x=' + xx + ' y=' +yy + ' height=' + ht + ' width=' + wd + '>' );
//-->
</script></div>

</layer><script>
	mytop = 0.44 * g_height; myleft = 0.47 * g_width; myheight = 0.12 * g_height; mywidth = 0.09 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.06 * g_height; mywidth = 0.09 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-272 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:233%;color:#F6BF69'>Low<br>
</span></div>

</layer><script>
	mytop = 0.06 * g_height; myleft = 0 * g_width; myheight = 0.06 * g_height; mywidth = 0.07 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='mso-line-spacing:"-272 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:233%;color:#F6BF69;mso-special-format:lastCR;
display:none'><br>
</span></div>

</layer></div>

</layer><script>
	mytop = 0.58 * g_height; myleft = 0 * g_width; myheight = 0.06 * g_height; mywidth = 1.13 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script>
	mytop = 0 * g_height; myleft = 0.01 * g_width; myheight = 0.04 * g_height; mywidth = 1.12 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%;mso-line-spacing:"-200 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17;mso-line-spacing:"-200 0 0";mso-margin-left-alt:17;
mso-text-indent-alt:17'><span style='font-family:Gadget;font-size:167%;
color:white'>&gt;&gt;&gt;&gt;PROMOTER--ATG-Exon1-Intron1-Exon2-Intron2 -
etc-3'UTR &gt;&gt;&gt;&gt;&gt;</span></div>

</layer></div>

</layer><script>
	mytop = 0.37 * g_height; myleft = 0.08 * g_width; myheight = 0.2 * g_height; mywidth = 0.13 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script language=JavaScript><!--
xx = 0.08 * g_width;
yy = 0.37 * g_height;
ht = 0.2 * g_height;
wd = 0.13 * g_width;
document.write(
'<img border=0 src="slide0003_image060.png" x=' + xx + ' y=' +yy + ' height=' + ht + ' width=' + wd + '>' );
//-->
</script></div>

</layer><script>
	mytop = 0.4 * g_height; myleft = 0.1 * g_width; myheight = 0.11 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b>&#4;</b></span><span style='font-family:Palatino;
font-size:233%;color:white;display:none'><b><br>
</b></span></div>

</layer><script>
	mytop = 0.05 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:Palatino;font-size:233%;
color:white;mso-special-format:lastCR;display:none'><b><br>
</b></span></div>

</layer></div>

</layer><script>
	mytop = 0.4 * g_height; myleft = 0.18 * g_width; myheight = 0.11 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b>&#4;</b></span><span style='font-family:Palatino;
font-size:233%;color:white;display:none'><b><br>
</b></span></div>

</layer><script>
	mytop = 0.05 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:Palatino;font-size:233%;
color:white;mso-special-format:lastCR;display:none'><b><br>
</b></span></div>

</layer></div>

</layer><script>
	mytop = 0.33 * g_height; myleft = 0.08 * g_width; myheight = 0.2 * g_height; mywidth = 0.13 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div><script language=JavaScript><!--
xx = 0.08 * g_width;
yy = 0.33 * g_height;
ht = 0.2 * g_height;
wd = 0.13 * g_width;
document.write(
'<img border=0 src="slide0003_image061.png" x=' + xx + ' y=' +yy + ' height=' + ht + ' width=' + wd + '>' );
//-->
</script></div>

</layer><script>
	mytop = 0.36 * g_height; myleft = 0.18 * g_width; myheight = 0.11 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
	mytop = 0 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:"\30D2\30E9\30AE\30CE\89D2\30B4 Pro W3";
font-size:233%;color:white'><b>&#4;</b></span><span style='font-family:Palatino;
font-size:233%;color:white;display:none'><b><br>
</b></span></div>

</layer><script>
	mytop = 0.05 * g_height; myleft = 0 * g_width; myheight = 0.05 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:center;mso-line-spacing:"-269 0 0";mso-margin-left-alt:
17;mso-text-indent-alt:17'><span style='font-family:Palatino;font-size:233%;
color:white;mso-special-format:lastCR;display:none'><b><br>
</b></span></div>

</layer></div>

</layer><script>
	mytop = 0.36 * g_height; myleft = 0.1 * g_width; myheight = 0.11 * g_height; mywidth = 0.01 * g_width;
	document.write( '<layer top=' + mytop + ' left=' + myleft + ' height=' + myheight + ' width=' + mywidth + ' >' );
</script>

<div style='text-align:left;font-family:Verdana;font-weight:normal;font-style:
normal;text-decoration:none;text-shadow:none;text-effect:none;mso-fareast-hint:
no;layout-flow:horizontal;color:black;mso-color-index:1;font-size:80%;
mso-text-raise:0%'><script>
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<div style='mso-line-spacing:"-233 0 0";mso-margin-left-alt:17;mso-text-indent-alt:
17'><span style='font-size:200%;color:#E9EB5D'><i>trans QTL</i></span><span
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<layer>
 <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=Helvetica size=3>This slide is
   illustrates two major types of QTLs that modulate variability in
   transcript-relative steady state abundance.</font><br>
   </td>
  </tr>
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   <td align=left colspan=1><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>
   </td>
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   <td align=left colspan=1><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">&nbsp; </span>The way
   in which an upstream polymorphism influences a downstream difference in mRNA
   abundance can be indirect. Effects can:</font><br>
   </td>
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   <td align=left colspan=1><font face=Helvetica size=3><span
   style="mso-spacerun: yes">&nbsp;&nbsp; </span>a.<span style="mso-spacerun:
   yes">&nbsp; </span>cross tissue types (a polymorphic liver enzyme may affect
   CNS gene expression)</font><br>
   </td>
  </tr>
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   <td colspan=1></td>
   <td align=left colspan=1><font face=Helvetica size=3><span
   style="mso-spacerun: yes">&nbsp;&nbsp; </span>b.<span style="mso-spacerun:
   yes">&nbsp; </span>cross time (the modulator is only expressed for one day
   during development but has permanent effects in adults)</font><br>
   </td>
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   <td align=left colspan=1><font face=Helvetica size=3><span
   style="mso-spacerun: yes">&nbsp;&nbsp; </span>c.<span style="mso-spacerun:
   yes">&nbsp; </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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