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What Is the Significance of an Allele Burden? An Expert Explains Abnormal Genes

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Published on February 11, 2019

Patient Power community member Julie wants to know, “why is understanding allele burden important in a JAK2 positive patient?” During this Ask the Expert segment, leading myeloproliferative neoplasm (MPN) expert Dr. Joseph Scandura, from Weill Cornell Medicine, explains what an allele burden is and how it relates to genetic mutations, why it’s important for doctors to know and how it’s assessed. Watch now to learn more.

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Transcript | What Is the Significance of an Allele Burden? An Expert Explains Abnormal Genes

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That's how you’ll get care that's most appropriate for you.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Here’s a question we got in from Julie. Julie says, “What is the significance of a very low allele burden in a JAK2 positive patient?” And may you could define allele for us too.

Dr. Scandura:              

Sure. So, as you know, we have some of our genes from mom and some of our genes from dad and the genes that we get are always in these two copies. And so, one copy from mom, one copy from dad, and they’re mixed and matched while we’re being sort of grown up from the embryo. But what happens in MPN is sometimes one of those copies, always starts with one of them, becomes mutated and that can be for instance, in the most common mutation, in the JAK2 gene, JAK2 V617F, a particular mutation that’s associated with abnormal function of the JAK2 gene product. And so, if we have just one copy in a cell, then one copy’s normal and one copy is mutant. 

So, if we are talking about that one cell, that variant allele frequency, so that’s the abnormal gene. The proportion of all the genes that are abnormal would be 50 percent, right? One abnormal, one normal. But now we think about all of the blood cells, trillions upon trillions of blood cells and then we have to take sort of an average of all of those cells. Some of them will be normal, some of them will be MPN cells, some of them will have one copy normal, one abnormal, some two abnormal, and some both normal. And so, when we look in a composite from a blood draw which is generally what people are sending, it’s a representation of how many abnormal alleles are present among all of the alleles of all of the DNA from the blood cells that’s been selected. 

So, what a low variant allele frequency means that the proportion of mutant alleles in that sample of your blood is low.So, low would be maybe 10 percent or 5 percent or something like that and what is the significance of that? It’s an area a little bit of some debate, but there’s certainly a number of studies that have shown a correlation between the variant allele frequency in blood and the disease type itself. So, for instance, essential thrombocythemia, or ET, generally, has a lower bearing allele frequency than myelofibrosis for the same mutation. And polycythemia vera is often in between.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.