A Self-Study Of My Child's Genetic Risk
genome & microbiome
Mad Ball is a carrier for a rare genetic disease that entailed the risk of having a child with a serious intellectual disability. But how much risk? Through careful self-investigation based on consumer genomics, a reasonable estimate turned out to be possible.
A Self-Study of My Childs Genetic Risk
This is a story about genetic disease in my family. This is a picture of me six years ago with my first child. I like most new parents I was worried about stuff. In this case some months earlier when I found out this was going to be a son, I was worried because I was worried about a genetic disease in my family.
This is a very traditional type of data, it’s a genetic pedigree of my family. This is what a genetic counsellor would look at. And the pattern here in this data is suggestive of an x link disease.
That’s me on the lower left and these are my two uncles, my mother’s brothers and they both have moderate intellectual disability, which mean their intelligence as adults is around like a six-year-old.
And they have other features like microcephaly, it’s clearly genetic and the cause was not known. So, we did know what was causing it. This pattern looks like something that son’s get and daughters might carry. So, the question is, is my mother a carrier?
The good news is that if she was a carrier or somehow, she lucked out and had two unaffected sons’, but the possibility remained that I might be a carrier. And so, when I found out I was having a son, I was worried.
I went and saw a genetic counsellor, traditional genetic testing, counseling, and the first line of defense is run tests. This isn’t helpful. It doesn’t rule out genetic disease. It just I came up negative and I don’t have fragile x carrier status.
And then the next thing you do as a genetic counsellor is apply base theorem. I don’t know if you’ve heard of bation statistics, but what you can do is take that family tree, pedigree data and get updated knowledge. Like without the knowledge of those two sons, my mother has a 50% chance of being a carrier. Crunch the numbers, and actually in the case of x-link disease, there’s now a 20% chance, which puts me at a 10% chance and a 5% chance to my son. That is assuming there is x-link disease here which is still uncomfortably high, but then I realized I had more data. I had data from 23andme. And so this is how I put that data to a new use.
Now, to explain how I used, I’m going to do a little discussion of my chromosomes. These are my X chromosomes. I got one from mom and one from dad, and the one I’m worried about is from mom, so it’s red.
My mom’s X chromosomes are actually a mix, so everything I get from her is a mix of stuff from grandma and stuff from grandpa. And I’m actually worried about stuff from grandma, because if you think through the logic here my uncle has got a Y from grandpa. So only pieces of the X chromosome from my mother that I am worried about are the pieces that I got from her from her mother.
Now, this is a hypothetical chromosome, but what’s cool is the 23andme data from my family I don’t have to have a hypothetical chromosome. I can figure out exactly what pieces that I got from grandma because we have that data from my family. So I used 23andme to compare my data to my grandfather.
By the time we had 23andme available my grandmother had passed away, but we can use process of elimination. What you get is literally a set of coordinates. Shared DNA here, shared DNA there, other pieces that are not shared DNA.
The visualization on the 23andme site looks like this and if we zoom in on the X chromosome, this is me versus grandpa, or if I want to switch back to my coloring scheme here, the regions in red is that I got from my grandmother that I’m worried about are still pretty big.
So, unfortunately with this analysis I’ve not updated my knowledge in a way that makes me more or less reassured, but there’s more information. There’s my brothers. So, I compared my brothers to my grandfather, again using 23andme tools. And in this case, I’m just going to show you one because it may be sufficient.
And this is him. This is my brother versus my grandfather, and the portion of DNA that he got from my grandmother is 94%. So this is fascinating because he has acted as a person that’s tested that DNA for me. He’s a great experimentalist. And he has since earned a PhD from Stanford in biophysics, so I think it’s safe to say that he did not inherit this genetic disease.
He responded via email, understanding the analysis saying, it’s a great chromosome. I recommend it highly.
And so, it’s safe. And what’s great then is we can even look at my own, an overlap there and he is effectively clear of every piece of X that I got from Grandma. We’ve got the exact coordinates. His grandma inheritance started before mine.
And so if there is an x-linked disease causing this trait, I went to zero percent chance which was really reassuring at the time. So that’s what I learned is that I ruled that out.
Now I’m going to give a spoiler and say I am a carrier. It turns out it wasn’t x-linked. I only found that out years after this so this saves me a lot of worries. But I’m actually a carrier of chromosome 1 for something like my uncle’s got whole exome testing.
And I feel that I can also take away some other lessons from this experience, and one of those is that having data about ourselves can matter a lot, but it’s like in unexpected ways. Because we did 23andme for all these other reasons like we didn’t collect our 23andme data thinking I’m going to do this chromosome region and analysis to rule out X link status. No, that was a retroactive realization I had on the data that we already had.
And the other thing that I see in this is just that I was only able to do this because I was able to compare my data to my family. If I had done 23andme on my own it would have been meaningless. I could never have done this analysis. This was only possible because it was something that we were doing together.
With that, I share my contact information. Some of these sort of emotions play a role in the work I do full-time is with Open Humans and I also care a lot about its issues, like whether we have a right to access all that interesting data about ourselves. So, this breakout session in the next session if you would like to come to it, and I’ll office hours about my work tomorrow at lunch.