The future of CNVs: sequence based resolution and links to human disease 2

Published on August 30, 2009 Updated on March 29, 2017   31 min

Other Talks in the Series: Biomarkers

Other Talks in the Series: Copy Number Variation

So what I would like to do is really kind of focus on where I think the field is heading with respect to copy number variation research and genome structure variation and highlight some of the limitations and excitement in the field with respect to future discovery. So the number of unanswered questions I think the most important is how we're going to actually activate genotype copy number variation particularly within these difficult duplicated regions and there is a need to develop new technologies specifically for that purpose. I and other labs really have argued that sequence resolution is the key for understanding the genetic basis of disease. I will highlight an example of this. And finally, I want to share with you some of the excitement really with respect to more complete ascertainment in terms of discovery of smaller variation using next generation sequencing technology and really the promise, potential promise of developing personalized CNV maps for individual genomes.
This slide actually highlights one of the limitations of many of the commercial SNP microarrays that are commonly used to detect copy number variation. So what I'm showing you are two histograms of both the Illumina and Affymetrix SNP platforms various versions, and the number of probes that are placed with insights that we've actually sequenced and confirmed with the base pair level as copy number polymorphic. Most groups would agree that you need at least two probes to accurately genotype copy number variation, preferably more than two probes to accurately genotype copy number variation once you know where it exists. So these two histograms actually show you that there is in fact a deficit of probes in regions of copy number polymorphism owing largely to the fact that they map to complex regions of genome and where there has been fewer probes laid down than the average. So typically, in these roughly 500 regions that we've sequenced, there is only about 60% of the sites that could be in principle adequately genotyped, and in fact, the actual number is much less than that. If you then looked at, for example, new insertion sequences or duplication intervals as opposed to deletion intervals, the number gets in fact considerably worse. In those cases, less than 20% of the existing or known sequence resolved duplications and new insertion sequences could be adequately resolved using these types of platforms.

The future of CNVs: sequence based resolution and links to human disease 2

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