why some illnesses and diseases “skip” a generation.


why some illnesses and diseases “skip” a generation.

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With X-linked conditions, meaning the gene is located on the X chromosome, sons will show the condition with only one copy, whereas a daughter will need two copies of that gene.

For example, let’s say a colorblind man has a daughter. His contribution to her is an X-chromosome. So his daughter will have one normal X and one colorblind X, she’s a carrier.

When this daughter eventually has kids, her sons will have a 50-50 chance of being colorblind, depending on which X-chromosome they inherit from her.

This is a gross simplification but here’s how I teach it in Grade 11 bio:

**Some basic facts:**

– DNA’s major function is to code for proteins in your body. It does a lot of other stuff related to this goal, but at the end of the day it’s [gene -> protein]. Proteins do the vast majority of the biochemical work. You have thousands of different ones, all coded for in your DNA.

– You get half your DNA from your mom and half from your dad in the form of 23 chromosomes from each

– Aside from X and Y, these two sets of chromosomes have all the same genes (same areas of the DNA coding for the same trait), so you have two copies of each gene.

– The two sets can have different versions of the genes, these versions are called alleles.

– Mom and dad also got two copies from their moms and dads and so on and so forth.

**Putting it together:**

I’ll use the example of a smell receptor, which is a protein that changes shape to send a signal when some other chemical hits it. If it has the right shape to match the chemical it detects, your brain will get a signal that it will interpret as “strawberry” or whatever.

Now we run three scenarios to explain how this affects a trait (here, it’s ‘smelling strawberries’):

– You get two ‘good’ copies of the strawberry smell gene from mom and dad. your nose has the receptors, you can smell strawberries, life is groovy.

– You get one ‘good’ copy and one ‘bad copy’. Maybe mom’s egg got hit with some radiation and messed up that little bit of DNA. That smell receptor won’t react to strawberries anymore, but hey, you’ve got dad’s good copy, so you can still smell strawberries. Maybe it’s not quite the same but you’ve still got the trait.

– You get two bad copies of the allele. Neither mom’s nor dad’s gene makes the right shape for your smell receptor. You will never know the joy of strawberry smell the way the rest of us do.

**Skipping a generation:**

It is entirely possible for a mom and dad who can both smell strawberries to have a kid who can’t. For this to happen, both mom and dad must have one good and one bad copy, so they’ve got the right receptors but by chance (50% per parent, so 25% chance overall), you ended up with their bad copies instead of their good one,

The same is true for mom and dad, the trait can hide for a long time before the right two people have a kid who is unlucky enough to get two bad copies.

**This is only one type of inheritance, there are others:**

What I’ve described here is an autosomal recessive inheritance. It can skip generations. Sometimes, though, the weird version of the gene causes a problem instead of just losing a trait. In this case, just one bad copy is enough. One example of this is Huntington’s disease, where the bad protein literally starts killing brain cells. We call this a dominant inheritance pattern. Dominant traits will never skip a generation since the moment someone doesn’t pass on the ‘bad’ copy, all the next generations automatically don’t have the problematic allele anymore.

You have two copies of every gene (except for most genes on the X-chromosome, which males only get one of). If you get two “bad” copies of a certain gene, obviously that’s going to lead to a bad outcome. But what happens if one copy is functional and the other isn’t? That depends on what the gene does. Sometimes, one bad copy can screw everything up. But sometimes, the bad copy just does nothing and the good copy can “fill in” for the bad one.

If just one bad copy is enough to cause problems, then anyone who carries that bad gene will have these problems. In that case, the disorder cannot skip a generation: if neither of your parents have the disorder, then they cannot have the bad gene (if they had it, it would show).

However, if you need *two* copies to experience the ill effects, then it is possible to carry a single copy of the gene without experiencing any issues. This means both your parents could be carriers without having the disorder, and if they both pass their bad gene copy onto you, now you have two bad copies and you get the disorder. And thus the disorder has skipped your parents’ generation. And maybe it skipped your grandparents too and a bunch more generations. Only those people in your family tree who received two bad copies would have had the disorder.

It depends on the disease.

If it is entirely genetic, there are a few reasons

Autosomal dominant means you only need one faulty gene and will affect both men and woman. These are conditions where you often see each generation affected.
Most of the common autosomal dominant conditions have something called high penetrance or complete penetrance. That means that if you have the faulty gene, you get the disease. For example, huntingtons disease is a 100% of people who have the faulty gene will get Huntington’s disease. Likewise for achondroplasia (most common form of dwarfism) and osteogenesis imperfects (the inherited brittle bone disease).

However there are some conditions which have reduced penetrance. An easy example is the BRCA1 gene. 80% of women with a faulty version of this get breast cancer. That means 1 in 5 don’t. Men with it have a 1 in 100 chance of getting breast cancer (men have breast tissue too!). So there are many unaffected.

Reasons why people maybe unaffected in different conditions are:
– they’ve inherited other genes that can be protective
– things about their environment or lifestyle reduce the chances. These can be obvious things, such as not smoking in those with a cancer predisposing conditions, or subtle things we have no control over
– very mild disease: the “missed generation” person may have very mild disease so it isn’t recognised
– if it not something that begins at birth or childhood, the person may die before they develop symptoms, so it looks like it skipped a generation

For other conditions that are only partially genetic (eg asthma) it is because there are a collection of genes that make it it more likely that they will develop the disease than someone who does not have a family history, but because of environmental factors and probably other inherited genes, it’s not a guarantee. But at the same time, these conditions can happen without a family history and occur anyway. Examples are things like asthma, type 1 diabetes, eczema. So you might see an affected family member somewhere else in the family, but it won’t be an every generation type line through the family tree