<html> <head> <meta http-equiv=Content-Type content="text/html; charset=macintosh"> <meta name=ProgId content=PowerPoint.Slide> <meta name=Generator content="Microsoft Macintosh PowerPoint 11"> <link id=Main-File rel=Main-File href="webqtl_demo2.ppt.htm"> <title>PowerPoint Presentation - Complex trait analysis, develop-ment, and genomics</title> <link title="Presentation File" type="application/powerpoint" rel=alternate href="webqtl_demo2.ppt.ppt"> <script> if ( ! top.PPTPRESENTATION ) { window.location.replace( "endshow.htm" ); } </script> <meta name=Description content=Aug-15-05> <link rel=Stylesheet href="master03_stylesheet.css"> <style media=print> <!--.sld {left:0px !important; width:6.0in !important; height:4.5in !important; font-size:76% !important;} --> </style> <script language=JavaScript src=script.js></script><script language=JavaScript><!-- gId="slide0003.htm" if ( !parent.base.g_done && (parent.base.msie < 0 ) ) { parent.base.g_done = 1; document.location.replace( parent.base.GetHrefObj(parent.base.g_currentSlide).m_slideHref); 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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%; 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:"-269 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> <img border=0 src="slide0003_image062.png" style='position:absolute;top:27.38%; left:4.9%;width:21.45%;height:21.37%'> <div style='position:absolute;top:27.38%;left:5.03%;width:20.92%;height:12.54%; filter:DropShadow(Color=#000000, OffX=1, OffY=1)'> <div class=O style='position:absolute;top:5.63%;left:6.32%;width:94.3%; 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>trans 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:83.22%;height:50.0%'><span style='font-size:200%;color:#E9EB5D;mso-special-format:lastCR;display:none'><br> </span></div> </div> </div> </div> <div id=NotesObj style='display:none'> <table style='color:white' border=0 width="100%"> <tr> <td width=5 nowrap></td> <td width="100%"></td> </tr> <tr> <td colspan=1></td> <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> <tr> <td colspan=1></td> <td align=left colspan=1><br> </td> </tr> <tr> <td colspan=1></td> <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> </tr> <tr> <td colspan=1></td> <td align=left colspan=1><br> </td> </tr> <tr> <td colspan=1></td> <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> </td> </tr> <tr> <td colspan=1></td> <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> </td> </tr> <tr> <td colspan=1></td> <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> </td> </tr> <tr> <td colspan=1></td> <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> </td> </tr> </table> </div> <script language=JavaScript><!-- function playList() { } //--> </script> </body> </html>