Anna Greka

Oh, thank you.

It's a great honor to be here and glad to chat with you, Eric.

Oh, absolutely.

Yeah, it's an interesting story.

In some ways, you know, in my TED talk, I highlight one of the important families of this story, a family from Utah.

But there's also other important families that are also part of the story.

And this is also what I spoke about in London when we were together.

And this is really a sort of a medical mystery that initially started on the Mediterranean island of Cyprus.

where it was found that there were many families in which in every generation, several members suffered and ultimately died from what at the time was a mysterious kidney disease.

This was more than 30 years ago.

And, you know, it was clear that there was something genetic going on, but it was impossible to identify the gene.

And then even with the advent of next gen sequencing, this is what's so interesting about this story.

It was still hard to find the gene, which is a little surprising, right?

You know, after we were able to sequence, you know, families and identify sort of monogenic mutations pretty readily, this was still very resistant.

And then it actually took the firepower of the Broad Institute.

And it's actually from a scientific perspective, an interesting story because they had to dust off the old fashioned Sanger sequencing in order to get this done.

But they were ultimately able to identify this mutation in a VNTR region of the MUC1 gene, the Mucin-1 gene, which I call a dark corner of the human genome.

You know, it was really, it's highly repetitive, very GC-rich, so it becomes very difficult to sequence through there with next-gen sequencing.

And so ultimately, the mutation, of course, was found.

And it's a single cytosine insertion in a stretch of cytosines that sort of causes this frame shift mutation and then early stop codon that essentially results in a neoprotein, like a toxic, what I call a mangled protein that sort of accumulates inside the kidney cells.