Dr. Alex Stewart: Well, my laboratory at the University of Ottawa Heart Institute is interested in pursuing the genetics behind cardiovascular diseases, including coronary artery disease and hypertension, among several others.
We're applying the Axiom Genotyping Solution to our research essentially as a seamless follow through to our previous use of the 6.0 arrays. Basically, what we've noticed is a dramatic improvement in the quality of our calls and the accuracy of the genotyping that has enabled us to impute a large number of SNPs.
Certainly, our focus has been on persons of European ancestry since they are a large fraction of the patients that we see at the Heart Institute. But, at the same time, we also serve a multiethnic population that makes up the Canadian population.
And so, very much so, we need to optimize our--the Axiom arrays for multiethnic populations in different--populations of different ancestry.
The Southeast Asian population in Ottawa is a very large cohort. And we also have a large representation among native populations in Canada, the aboriginal population.
So, you know, we definitely have to be able to discover the genetic variants that contribute to heart disease in those populations. And we've found in fact that some of these variants are quite distinct from those you find in persons of European ancestry.
Certainly, our discovery of common variants for coronary artery disease have shown us that they contribute to about 13 percent of the heritability, which means that there's a large amount of missing heritability that is yet to be discovered.
So, for us, the Axiom platform that will enable genotyping rare variants is of enormous importance because it happens that these rare variants often carry quite a bit more risk and have stronger effects.
Certainly, the validation of the rare variants that Affymetrix has done is very important to us because we don't want to be pursuing rare variants that turn out to be spurious variants.
It's going to be a quantum improvement in our ability to genotype because certainly a large component of the risk for common diseases is carried by rare variants.
When we discover a genetic variant associated with disease, the fact that we can use the Axiom platform to customize our fine mapping of that region to discover the functional variants is very important to us.
And what we're aiming to do is to use this platform in a cost-effective way to be able to do some fine mapping and to better characterize our low side.
The fact that the Axiom platform is cost effective is a fundamental advantage of this platform because, currently, funding is very tight. And clearly, to be able to perform a fine mapping in a cost-effective way will enable us to do far more samples.
And the limitation of these genome-wide association studies are that it takes many samples to be able to reach the level of confidence to be sure that an association is real, so very advantageous.
We have been very pleased with the implementation of the Axiom solution in our laboratory.
Axiom arrays give us, you know, remarkable genotyping quality and reliability. The importance of it is that, if you want to impute non-genotype SNPs, your limitation is how well you genotype. And the better you genotype, the better you impute. So, it's been very important.
We've been able to genotype thousands of samples on the Axiom platform in a very short time. And we've had only to dedicate a single technician to this task, whereas before, we had four technicians doing the genotyping. So, it has become far more cost effective and of much higher throughput.
The Axiom Assay performance and data quality has been exceptional. Really, to be able to impute SNPs that have not been genotyped requires the highest level of quality assurance, the highest level of performance. And we've been able to achieve this.
And this has enabled us to impute 11 million snips on average using the Axiom platform. And this has increased the power of this assay enormously.
Imputation in genome-wide association studies has become essential to be able to get complete coverage and as much coverage as possible.
Imputation is limited by the quality of the genotyping. Ninety-eight percent call rates will allow you to impute down to an allele frequency of 2 percent. And we've found that the Axiom platform has enabled a much higher level of imputation that we could achieve with previous platforms.
And so, we're very excited by this technology because it's an essential component of the GWAS approach.
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CNPG_Dr-Alex-Stewart-The-Axiom-Genotyping-Solution-GWAS-imputation-and-cost-effective-customization