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   PPT - Copy Number Variation PowerPoint Presentation, free download - ID:5087338
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What do we mean by “ copy number variation? ”. “ normal ”. deletion. duplication of one gene. duplication of several genes. duplication of part of a gene...."name=description><meta content="copy number variation, copy number variation ppt, powerpoint, presentation"name=keywords><link href=https://www.slideserve.com/milla/copy-number-variation rel=canonical><link href=https://www.slideserve.com/milla/copy-number-variation hreflang=en rel=alternate><link href=https://fr.slideserve.com/milla/copy-number-variation hreflang=fr rel=alternate><link href=https://www.slideserve.com/milla/copy-number-variation hreflang=x-default rel=alternate><meta content="Copy Number Variation"name=abstract><meta content=milla name=author><meta content="Copy Number Variation - by milla"name=copyright><link href=https://image2.slideserve.com/5087338/copy-number-variation-n.jpg rel=image_src><meta content=on http-equiv=x-dns-prefetch-control><meta content=117162848378808 property=fb:app_id><meta content=article property=og:type><meta content=https://www.slideserve.com/milla/copy-number-variation property=og:url><meta content="Copy Number Variation"property=og:title><meta content="Copy Number Variation. Eleanor Feingold University of Pittsburgh March 2012. GCTC ATATATAT TTG. kb - Mb (gene or gene region). What do we mean by “ copy number variation? ”. “ normal ”. deletion. duplication of one gene. duplication of several genes. duplication of part of a gene."property=og:description><meta content=SlideServe property=og:site_name><meta content=https://image2.slideserve.com/5087338/copy-number-variation-n.jpg itemprop=image property=og:image><meta content="Oct 03, 2014"property=article:published_time><meta content=milla property=article:author><meta name=twitter:card value=player><meta name=twitter:site value=@SlideServe><meta class=twitter_player name=twitter:player value=https://www.slideserve.com/embed/5087338><meta name=twitter:player:width value=342><meta name=twitter:player:height value=291><meta value="Copy Number Variation"class=twitter_title name=twitter:title><meta class=twitter_image name=twitter:image value=https://image2.slideserve.com/5087338/copy-number-variation-n.jpg><link href=//www.slideserve.com rel=dns-prefetch><link href=//thumbs.slideserve.com rel=dns-prefetch><link 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Eleanor Feingold University of Pittsburgh March 2012. GCTC ATATATAT TTG. kb - Mb (gene or gene region). What do we mean by “ copy number variation? ”. “ normal ”. deletion. duplication of one gene. duplication of several genes. duplication of part of a gene.<div class=mb-2>Uploaded on <time datetime=2014-10-03 itemprop=datePublished> Oct 03, 2014 </time></div><div class="d-inline-flex user-height"style="margin-top: 15px;"><img class="profile img-fluid img-thumbnail mr-2"alt=milla itemprop=image src=//www.slideserve.com/photo/31748.jpeg><ul class="list-user list-unstyled list-user"><li class="user-name font-weight-bold"><a href=/milla itemprop=url rel=author title=milla> Milla Jes </a><li style="margin-left: 5px;"class=follow><button class="btn btn-sm btn-outline-primary"onclick=followuser(31748,'milla','i','on'); rel=nofollow>+ Follow</button></ul></div><ul class="ss-tag-group mt-3"><li><a class=ss-tags href=/search/intensity-ppt-presentation> intensity </a><li><a class=ss-tags href=/search/total-intensity-ppt-presentation> total intensity </a><li><a class=ss-tags href=/search/cnv-regions-ppt-presentation> cnv regions </a><li><a class=ss-tags href=/search/de-novo-ppt-presentation> de novo </a><li><a class=ss-tags href=/search/total-intensity-trisomic-ppt-presentation> total intensity trisomic </a><li><a class=ss-tags href=/search/assay-copy-number-variation-ppt-presentation> assay copy number variation </a></ul></div></div><div class=fb-comments data-colorscheme=light data-href=https://www.slideserve.com/milla/copy-number-variation data-numposts=10></div></div><div class="col-md-12 col-sm-12 download-ppt"id=Download_ppt><span> Download Presentation <img style="height: auto;"alt height=50 id=download src=/img/output_cBjjdt.gif width=50> </span><h2>Copy Number Variation</h2><div style="min-height: 105px;"id=d-text></div><div class=ad-area><div style=height:500px;width:100%;><script async src=//pagead2.googlesyndication.com/pagead/js/adsbygoogle.js></script><ins class=adsbygoogle data-ad-client=ca-pub-3976764401535897 data-ad-slot=1413580485 style=display:inline-block;width:336px;height:280px> </ins><script>(adsbygoogle = window.adsbygoogle || []).push({});</script></div></div><div class="text-center mb-5 mt-4">- - 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. qunyuan zhang,ph.d. division of statistical genomics department of genetics </span> </a></div></div><div class="col-12 pt-5 pb-2"><div class="row view-pagination"><ul class="pager row view-pagination"><li class="disabled align-items-center npbuttons"><i class=ss-icon-chevron-left> </i><li><p><span class=j-current-slide id=current-slide> 1 </span> of 5</p><li class="align-items-center npbuttons"><i class=ss-icon-chevron-right> </i></ul></div></div></div><div class="tab-pane mt-2"id=moreby><div class="row justify-content-center"id=byusersect></div></div></div></div></div></div><h5 class="m-2 font-weight-normal">Presentation Transcript</h5><hr class="col-12 mt-1"><ol id=tscript><li value=1><p><strong> <a title="copy number variation"href=https://image2.slideserve.com/5087338/copy-number-variation-l.jpg target=_blank> Copy Number Variation </a> </strong> Eleanor Feingold University of Pittsburgh March 2012</p><li value=2><p><strong> <a title="what do we mean by copy number variation"href=https://image2.slideserve.com/5087338/what-do-we-mean-by-copy-number-variation-l.jpg target=_blank> GCTCATATATATTTG </a> </strong> kb - Mb (gene or gene region) What do we mean by “copy number variation?”</p><li value=3><p><strong> <a title="copy number variation in a gene or gene region"href=https://image2.slideserve.com/5087338/copy-number-variation-in-a-gene-or-gene-region-l.jpg target=_blank> “normal” </a> </strong> deletion duplication of one gene duplication of several genes duplication of part of a gene Copy number variation in a gene or gene region</p><li value=4><p><strong> <a href=https://image2.slideserve.com/5087338/slide4-l.jpg target=_blank title=slide4> Classical copy number study types </a> </strong> Cancer genetics Clinical pediatrics What Find chromosomal segments (usually large ones) that are duplicated and/or deleted in tumor cell lines Why Learn something about cancer biology or Implications for treatment and prognosis What Detect inherited or de novo deletions in individuals Why “Diagnose” birth defects</p><li value=5><p><strong> <a href=https://image2.slideserve.com/5087338/slide5-l.jpg target=_blank title=slide5> 1) Collect cases and controls. </a> </strong> 2) “Genotype” everyone at a CNV. 0 4 2 1 2 5 0 1 1 4 1 16 3 2 1 2 0 3) Test genotype/phenotype association. And now:Genetic association studies for CNVs</p><li value=6><p><strong> <a title="how do we assay copy number variation"href=https://image2.slideserve.com/5087338/how-do-we-assay-copy-number-variation-l.jpg target=_blank> How do we assay copy number variation? </a> </strong></p><li value=7><p><strong> <a href=https://image2.slideserve.com/5087338/slide7-l.jpg target=_blank title=slide7> Generation 1 - Array CGH </a> </strong> What Microarray of clones (e.g. BACs) Usually on glass slide Competitive hybridization of test and reference samples. Measure fluorescence ratio clone by clone. Limitations Large clones. Sparse coverage. High noise due to spotting process.</p><li value=8><p><strong> <a href=https://image2.slideserve.com/5087338/slide8-l.jpg target=_blank title=slide8> Generation 2 - SNP chips </a> </strong> What High-throughput SNP genotyping platforms (e.g. Affymetrix, Illumina) Disadvantages Technology was never intended for measuring copy number. SNPs on chip selected to avoid CNV regions by design. Advantage Hundreds of thousands of points of info.</p><li value=9><p><strong> <a href=https://image2.slideserve.com/5087338/slide9-l.jpg target=_blank title=slide9> Generation 3 - SNP chips with CNV markers </a> </strong> (Affy 6.0, Illumina 1M) Advantages SNPs in known CNV regions are now included. Also have “non-polymorphic SNPs” (SNs?) Illumina 1M markers in 10K regions of various types and sizes Affymetrix 200K probes in 5K known large CNV regions 700K probes “evenly spaced along the genome”</p><li value=10><p><strong> <a href=https://image2.slideserve.com/5087338/slide10-l.jpg target=_blank title=slide10> Generation 4 - </a> </strong> (Illumina 2.5M, 5M) Changes Got rid of the non-polymorphic markers. Special coverage of CNV regions??? Are these better or worse for CNVs than the previous generation?</p><li value=11><p><strong> <a title="what data do these technologies give us and how do we use it"href=https://image2.slideserve.com/5087338/what-data-do-these-technologies-give-us-and-how-do-we-use-it-l.jpg target=_blank> What data do these technologies give us, and how do we use </a> </strong> it?</p><li value=12><p><strong> <a href=https://image2.slideserve.com/5087338/slide12-l.jpg target=_blank title=slide12> Standard genotyping </a> </strong> Genotype information is in the angle (relative intensity of the two alleles). Copy number information is in the distance from the origin (total intensity). BB AB AA</p><li value=13><p><strong> <a href=https://image2.slideserve.com/5087338/slide13-l.jpg target=_blank title=slide13> In theory </a> </strong> AAB AAA ABB AA AB A BB BBB B null</p><li value=14><p><strong> <a href=https://image2.slideserve.com/5087338/slide14-l.jpg target=_blank title=slide14> But when you look at the data … </a> </strong> AAA and AA trisomic (Down Syndrome) AAB disomic AB ABB BBB and BB</p><li value=15><p><strong> <a href=https://image2.slideserve.com/5087338/slide15-l.jpg target=_blank title=slide15> disomic </a> </strong> trisomic total intensity (trisomic) total intensity total intensity (disomic) All SNPs on chromosome 21</p><li value=16><p><strong> <a href=https://image2.slideserve.com/5087338/slide16-l.jpg target=_blank title=slide16> In theory </a> </strong> AAB AAA ABB AA AB A BB BBB B null</p><li value=17><p><strong> <a href=https://image2.slideserve.com/5087338/slide17-l.jpg target=_blank title=slide17> In practice </a> </strong> A B null</p><li value=18><p><strong> <a title="so how are copy numbers called"href=https://image2.slideserve.com/5087338/so-how-are-copy-numbers-called-l.jpg target=_blank> So how are copy numbers called? </a> </strong> Look for runs of SNPs that are high or low in intensityMany available algorithms e.g. HMM, CBS, change-point</p><li value=19><p><strong> <a href=https://image2.slideserve.com/5087338/slide19-l.jpg target=_blank title=slide19> Basic picture </a> </strong></p><li value=20><p><strong> <a href=https://image2.slideserve.com/5087338/slide20-l.jpg target=_blank title=slide20> Komura et al. </a> </strong> Genome Research 2006</p><li value=21><p><strong> <a href=https://image2.slideserve.com/5087338/slide21-l.jpg target=_blank title=slide21> More complex examples (cancer genetics) </a> </strong> Peiffer et al. Genome Research, 2006</p><li value=22><p><strong> <a href=https://image2.slideserve.com/5087338/slide22-l.jpg target=_blank title=slide22> amplification </a> </strong> total intensity Angle (genotype info) AA AB BB</p><li value=23><p><strong> <a href=https://image2.slideserve.com/5087338/slide23-l.jpg target=_blank title=slide23> deletion </a> </strong> deletion</p><li value=24><p><strong> <a href=https://image2.slideserve.com/5087338/slide24-l.jpg target=_blank title=slide24> total </a> </strong> intensity high over whole chromosome 3 genotype groups Extra copy of whole chromosome</p><li value=25><p><strong> <a href=https://image2.slideserve.com/5087338/slide25-l.jpg target=_blank title=slide25> LOH </a> </strong> No copy number change, but a region of homozygosity (LOH)</p><li value=26><p><strong> <a href=https://image2.slideserve.com/5087338/slide26-l.jpg target=_blank title=slide26> Basic picture </a> </strong> Wang et al. Genome Research, 2007</p></li><p><p></p><li value=29><p><strong> <a href=https://image2.slideserve.com/5087338/slide29-l.jpg target=_blank title=slide29> Chromosome 9 </a> </strong></p><li value=30><p><strong> <a title="a few statistical issues to think about there s still a lot to do"href=https://image2.slideserve.com/5087338/a-few-statistical-issues-to-think-about-there-s-still-a-lot-to-do-l.jpg target=_blank> A few statistical issues to think about … (there’s still </a> </strong> a lot to do)</p><li value=31><p><strong> <a href=https://image2.slideserve.com/5087338/slide31-l.jpg target=_blank title=slide31> Many run-calling algorithms are oriented towards clinical </a> </strong> applications. Many CNV detection algorithms are very conservative - aim for zero false positive rate. Most use normalization methods that assume a large reference population is not available. Many use models that make assumptions about what kinds of variation are likely (e.g. cancer).</p><li value=32><p><strong> <a href=https://image2.slideserve.com/5087338/slide32-l.jpg target=_blank title=slide32> Family data should be modeled together. </a> </strong> CNV “calls” will be much more accurate if you use the whole family, but the model you use should depend on whether you are expecting de novo mutations or not. For some diseases you’ll expect associations with de novo changes. For others you might expect inherited variants.</p><li value=33><p><strong> <a title="how do we group cnvs for association testing"href=https://image2.slideserve.com/5087338/how-do-we-group-cnvs-for-association-testing-l.jpg target=_blank> deletion </a> </strong> deletion deletion deletion duplication How do we group CNVs for association testing?</p><li value=34><p><strong> <a href=https://image2.slideserve.com/5087338/slide34-l.jpg target=_blank title=slide34> Separate methods for deletions? </a> </strong> Deletions are easier to detect than other changes. Deletions are likely to have simpler biological effects.</p><li value=35><p><strong> <a href=https://image2.slideserve.com/5087338/slide35-l.jpg target=_blank title=slide35> The most important one … </a> </strong> The technology is still NOT intended for reliably and comparably measuring total intensity! Total intensity numbers are very sensitive to DNA source, sample handling, etc., so extreme measures must be taken to ensure that cases and controls are comparable.</p></ol></div><div style="width:100%;height:300px; margin-top: 5px;"><script async src=https://pagead2.googlesyndication.com/pagead/js/adsbygoogle.js></script><ins class=adsbygoogle data-ad-client=ca-pub-3976764401535897 data-ad-format=auto data-ad-slot=9256152738 data-full-width-responsive=true style=display:block> </ins><script>(adsbygoogle = window.adsbygoogle || []).push({});</script></div></div></section><div id=suggestion><div class=ss-peekin id=suggestion-box style=display:none;></div></div><script>var LeadEnabled = 'false';
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