59. DNA, Genes and Rare Chromosome Disorders: What Does It All Mean?

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Lisa: I wanted to call this episode… “Genes Genes What Do They Means?” but I wanted to give this topic the respect and maturity it deserves. I can’t guarantee that I won’t throw a few silly asides in here somewhere along the way because.. well, puns are my genes. Unlike my husband. He keeps trying to get in but, I have a headache. All, my jeans are way too tight lately. I’m strictly yoga pants right now. Ha. See, less than a minute in and it’s already started.

This episode is in honour of Rare Chromosome Disorder Awareness Day… we’re broadcasting this today, on the actual day, June 16th, 2022.

Rare Chromosome Disorder Awareness Day was created, I’m reading the tagline from their website, “to celebrate, and educate and shine bright together.”

Well, it is a very BRIGHT life over here, so I can obviously get behind that. It’s also meant to try to reach out to anyone who needs help in some way or to those who might not have heard of chromosome and gene disorders. I mean, I find it hard to believe there are people who haven’t heard of chromosome disorders, but I guess they’re out there. And ya, there are definitely loads of rare gene disorders that most people have never heard of. So, awareness days like these definitely serve a purpose.

I did episode about awareness days. I don’t think it was an entire episode. I think I just touched on it. The IT being that there are people in the disability community who aren’t huge fans of awareness days. They call them kind of useless when they just draw attention to certain diseases or disorders without any purposeful action. Like, awareness days can create apathy by maybe desensitizing people. Or by even sensationalizing diseases with no real end game. But I think there is value in properly educating communities outside our own, about various disorders and diseases with the intention of thoughtfully educating with updated and relevant, scientific and medical and social information and also creating support for individuals and families through actual awareness and understanding.

So today’s episode is my attempt to share a bit about what I’ve learned about genetics and chromosomes, and more specifically about what chromosome disorders are. So, let’s jump in.

Intro

First and foremost, I’m not a scientist. I was an average student at best in high school when it came to science class. I actually had a mad crush on my grade 11 biology teacher. My Laval. Mmmmm… He was adorbs. My chemistry teacher? Not so much. Anyway. I’m a teacher myself. But that didn’t help me figure out any of this sciencey diagnosis stuff. Like at all. There’s a good reason why I didn’t teach beyond third grade.

Anyway, when we got Avery’s diagnosis, it was super confusing and completely overwhelming. And I’m not referring to the emotional confusion. That’s a whole other thing. I’m specifically referring to the biology of it all. I legitimately had to relearn basic
biology and chemistry. And even then, I had a million questions. Funny enough, Avery’s geneticist left the business to retire shortly after receiving us as patients. Coincidence? I’m not so sure.

So today, I thought I’d share a very basic, paired down, mini lesson or perhaps a review, for some of you, about Chromosomes
as they relate to chromosome disorders.

Genetics is a massive topic. And I only know that bare minimum. So, here are just 10 things to maybe help create a foundation of understanding.

Okay…

1. Let’s start with DNA. Humans and all living things have DNA. I like to think of it as our “recipe.”. A little bit of this, a little bit of that and bam… put me on a plate and call me Lisa. I’ve used the example of “puzzle pieces” before too. We all have a bunch of individual pieces that, when you put them all together, it’s makes a human. And when a piece is missing or damaged in some way, this can make the puzzle look disordered or different than intended. But I’ll get to that, the disordered bit, in a minute.

The information in your DNA, are made up of “genes”…genes are the small sections of DNA that have different functions. Each gene or section of DNA is encoded for or responsible for something specific about us.

We have two copies of every gene, one on each chromosome in a pair of chromosomes.

Genes give our cells the instructions for producing proteins. And it’s the proteins that drive our bodily functions, like digesting food, or building cells, or moving our muscles or whatever.

DNA is arranged like two intertwined ropes, you know that familiar structure we’ve all seen in science call, a double helix.

DNA is the most unique and identifying factor about us—it helps determine what color eyes we have, how tall we are, and how likely we are to have certain health problems.

What you might not know and what is so cool is that 99% of DNA sequences are the same among all people. Like, we’re really so closely related genetically to each other. It’s wild. This means, it’s just 1% of our DNA that sets us apart. It’s 1% of our DNA that makes us, uniquely us. And determines our traits.

That leads me to number 2. Which is traits. Traits are what make DNA Unique. Traits are the “observable” characteristics. Like brown eyes or blue eyes. Tall or short. Long eyelashes or short eyelashes. Things like that. That 1% of genetic difference gives our bodies information that results in differences from person to person. Otherwise we’d just be exact replicas. Clones.

3. Genes determine our traits. And our traits are what make us, us.

Genes are packaged into tightly wound lengths of DNA called chromosomes. Picture a gummy worm bound in the centre with a tight string. And now I want a sour gummy. God, the power of suggestion. Anyway, humans have 46 chromosomes in 23 distinct pairs.

22 pairs are called autosomal chromosomes, and these either dominant or recessive genes determine your body’s makeup.

And the 23rd pair of chromosomes, the sex chromosomes, determines whether you are born male or female. Females have a pair of XX chromosomes, while males have a pair of XY chromosomes.

Each individual chromosome can contain hundreds or thousands of wee little genes. Like, when you stop and think about that, it’s a bloody miracle that the recipe doesn’t get mixed up more often. Right? There’s lot going on there. I can’t even let myself ponder it all too long because it breaks my brain.

Anyway, one copy of each chromosome, think, little gummy worm, in your set of 23 pairs of gummies, is inherited from each parent, which means that you inherit one copy of each gene or ingredient, if you’re following the recipe analogy, from your mother and one copy from your father. So like, you’ll get let’s say a copy of one gene for brown eyes from your mom. And maybe one gene for blue eyes, just as an example, from your dad. And then depending on which copy gets added to the mixing bowl of batter that will become you, you might come out of the oven with brown eyes or blue eyes.

If my biology teacher heard this, he’d fail me. Sorry Mr. Laval. FYI… he came out of the oven with brown eyes. Warm, pools of chocolatey brown eyes. Just sayin.Let’s talk rare diseases now. When there’s a mistake in the DNA. Like a difference from the expected sequence of a gene, this is called a variant or a mutation. It’s not always a bad thing. It just depends on what it is. All of us have some variants, and we most often won’t even know it. It’s the variants that are harmful that can cause or increase our risk for certain diseases or disorders.

4. The nitty gritty. How do mistakes get made? Variants can be inherited from parents, or they can just happen spontaneously. When they have no hereditary history, like, they haven’t been passed down and the mutation just happened spontaneously, that is called a de novo mutation. This was the case for Avery. We have no idea where her chromosome… oh and just as a tiny FYI, it’s Chromosome with an M not Chromosome not chromosome with an n or chroma zone. Just in case you missed that. Oh, yeah her chromosome disorder was random. Both Adrian and I were tested and that period of waiting to see if one of us was the carrier, was extremely stressful.

And let me just say, and be very clear, if you are a carrier, it is not your fault. You didn’t do anything wrong. There is no blame. We didn’t get tested to point the finger. It’s important to know if there’s a familial or hereditary origin so that if you are considering having more children, you are aware. And also, so that
any siblings of your affective child will have this information when it’s time for them to consider starting a family.

If the mutation is indeed de novo, then where did it come from? Excellent question. And one that we don’t really have an answer for. It could be from environmental factors like toxins in the water or radiation or who the hell knows?

6. How is genetic testing done? Um, there’s a lot here. Nothing I can explain better than you can just read about for yourself. I’ll put a good link in the show notes. But basically, it’s a blood test. When we had Avery’s done, our family doctors suggestion when she first noticed some signs in Avery that there could be something going on genetically, there wasn’t anywhere in Canada to get this done. The lab work was sent to the states. It was called a micro array test which looks for anomalies in the genetic coding. I don’t know what the turnaround time is now, but back in 2007 it was a few months before we got results. Shortly after that, that’s when Avery’s dad and I had our genetics tested to see if we were carriers.
7. What is Avery’s specific genetic profile? Avery was diagnosed with a rare genetic disorder via microarray testing. Her diagnosis: unbalanced chromosomal translocation between 3p25.3 and 9p21.3

3P deletion of 3p26.3—3p25.3 (approximately 9.1 MB)
9P duplication of 9p24.3-9p21.3

This is how I remember the geneticist describing this to me and they’re with me because I’m going to completely butcher it, but as explained to me when the two strands of Chromosome three, one for mom and one from Dad, were lining up to duplicate, they pulled apart incorrectly and a portion of one end of one chromosome three strand of chromosome three was damaged and broke off. In the meantime, there was something funky going on over at Chromosome nine. A section of one strand of chromosome nine, the end bit, duplicated itself, I have no idea why or how, and that extra bit of Chromosome material, broke free and migrated across time and space to attach itself to the vacant end portion of the damaged Chromosome three strand. That’s forming an odd new Chromosome three Chromosome nine combo… Fancy translocation. This means, there is one completely typical an intact strand of chromosome three in the partnership as well as a typical strand of chromosome nine. This combination is
kind of bonkers when you think about everything that had to happen to make this occur. Thank God it did because… Avery.

And according to the geneticist, she was surprised that Avery wasn’t more severely affected negatively by this unprecedented combination. By all accounts, a combination like this should’ve had devastating effects. But that’s the thing, we never know how all of the factors, and I’m talking about the typical and functioning DNA, that were part of her original recipe, Plus the early supports in place, the whole nurture part of the equation, we don’t know how all of that will come into play. Her syndrome is kind of mind blowing.

8. What is a syndrome? A syndrome, like Down syndrome, to name one that most people have heard of, is a chromosome disorder, also known as trisomy 21. It occurs when there’s an abnormal cell division involving chromosome 21. It happens when there are three gummy worms of chromosome 21 instead of two. The extra genetic material is responsible for the characteristic features of Down syndrome.

A syndrome will only receive a name when a number of people present with the same missing or duplicated chromosomal material. At the time of Avery’s diagnosis, she was the only known person with er particular genetic combination, so no “official” name to her disorder has been given. However, since then, there are have been a lot more kids born with her particular deletion of chromosome 3 and THAT has now been called, 3P Disorder. So sometimes, for ease of discussion, I’ll just use that as the NAME of her chromosome syndrome. Otherwise, I just refer to it as a Chromosome Disorder in general.

9. Okay, so… Let’s put all the recipe stuff together, and bake a person together. Just as a final simple sum up. Plus I’m starving.

So both parents throw chromosomes into a bowl. That makes 46 individual chromosomes that pair up to make 23 sets. Each set is an ingredient in making a new person. Both parents throw in something sweet. One adds chocolate chips, the other add raisins. But if chocolate is dominant and raisins are recessive in this recipe, the cake person with be chocolatey. No raisins. Which is good because raisins do not belong in cake in my opinion. And if one of the ingredients happens to be stale or expired, for lack of a better example, it can alter the recipe. Like maybe the baking soda is old, the cake won’t rise like it was intended to in the recipe. This is a defect. But it doesn’t mean the cake won’t still be tasty. It just be look and taste different than in the cook book. In some cases though, the recipe really needs fresh baking soda or maybe baking powder, I never know which is for what, and the cake just won’t work out, and you’ll have to start again. It happens. It’s sad and hard when it happens to you as a parent, but it happens for a reason. Our body recognizes the mistake in the code, the recipe and starts over and starts a new cake. Which comes out of the oven, sweet and tasty and perfect and sometimes, perfectly imperfect. Which is just as delicious.

My biology teacher might not be impressed with me today but my home ec teacher, Mrs. Ambrazak would be proud of me.

10. I don’t have anything for number ten. Um. I could maybe make something up but instead I’ll say, science is cool. And life is so fascinating. Isn’t it? If I was smarter and my brain could handle the complexities of it all, I’d have totally gone into the sciences. But alas, the recipe for my intellect had more “creativity” sprinkled in, and less “critical thinking.” But that’s okay. We can’t all be scientists. And on that note, when I was typing out the outline for this episode, the word scientists, autocorrected to science tits and I laughed. So that’s just further proof that my brain isn’t cut out for serious sciencey stuff. Annnnnd, I’m okay with that.