Extra or Missing Chromosomes

Why are some chromosomal abnormalities more devastating than others? For example Trisomy 13 versus xyy. I figure it has to do something with the genes located on those chromosomes but what genes on those chromosomes make it so devastating to have extra copies?

- A high school teacher from Florida

February 15, 2007

You're definitely on the right track. It isn't the chromosome but the genes on the chromosome that matter.

Some genes on the extra chromosome will be more harmful than others. But for the most part, we don't know which are the harmful genes.

But we do know that larger chromosomes are more likely to have the harmful genes. Why? Because larger chromosomes have more genes in general.

Take chromosome 2 for example. It's one of the largest chromosomes. Fetuses that have an extra chromosome 2 usually die during the first trimester of pregnancy.

On the other hand, extra copies of two of the smaller chromosomes, 21 and Y, are better tolerated. Neither seems to have genes that are deadly when there's an extra copy.

Of course, tolerated isn't the same as no effect. An extra Y may make a person taller or more aggressive.

And you've probably heard of the disease where people have an extra chromosome 21. Or may even know someone. It's called Down syndrome.

But size isn't always everything. For example, chromosome 22 is one of the smallest chromosomes and an extra copy is deadly.

So except for chromosome 21 and the X and Y chromosomes, every chromosome has at least one gene that is devastating at three or more copies.

But why does having extra genes and extra chromosomes matter anyway?

Because our bodies are fine tuned machines that do best with the right amount of genes. To understand why this is, let's go into a bit of detail about genes and chromosomes.

We humans have 23 chromosomes and, except for the X and Y chromosomes in men, we have two copies of each one of them (for a total of 46). We get one copy of each from mom and one from dad.

Chromosomes carry your DNA, your body's instruction book. DNA has directions for your hair color, your eye color, your height, nearly everything!

Genes are also on chromosomes. The genes are like chapters in the DNA instruction book. And proteins are what the instructions are for.

Let's think about an instruction book for how to make a car. There needs to be a chapter on how to make the wheels, the engine, the seats, etc.

Each gene is one of these chapters. Genes carry all the instructions for each individual part of the car -- you.

The proteins would be the wheels, the engine, the seats, etc. The product of each gene. In order for the car to work correctly, all the parts need to be there and in the right amounts.

Let's get back to our question: why do extra genes make a difference? Well imagine a car with an extra wheel but not an extra set of brakes. You would crash!

There are genes like this too. For example, the VEGF gene has the instructions for blood vessel development. An extra copy of VEGF is lethal.

But not every part of the car is important to how the car works. An extra cup holder wouldn't be a big deal. Or an extra seat belt.

Again, we are the same way. Having extra working genes for eye color doesn't matter much. Sure your eyes may be green or brown instead of blue (click here for more details). But you can still see well.

So, we can tolerate the Y chromosome and chromosome 21 because they don't have any genes that are deadly with an extra copy. And we explained that big chromosomes are deadly because they all have at least one gene where three copies are deadly.

The exception to all this is the X chromosome. Since the X chromosome is large, we would expect an extra copy to be deadly. But this isn't the case. Why not?

The extra X is turned off. This happens only with the X chromosome (not chromosome 1 or 2 or 3 or...) to make up for the fact that women have more X chromosomes than men.

Women have two X chromosomes. Men have one X chromosome and one Y chromosome.

The body has found a way to deal with the extra X in women. It's called X inactivation (click here to learn more).

X inactivation is like the mute button on your TV. When the TV is muted you can still see the picture, but can't hear the sound. When the X is inactivated, it is still in each cell. The body still "sees" that the muted X is there, but can't "hear" the genes on the muted X.

This muting system is very general and works in both men and women. All extra X chromosomes are muted.

So if you are a woman and have three X chromosomes, two of your chromosomes are muted. If you are a man and have two X chromosomes and one Y chromosome, one of your X chromosomes is muted.

But we know that the X muting isn't perfect. Women who are XXX (called Triple X syndrome) and men who are XXY (called Klinefelter's Syndrome) may be taller and have disproportionately longer arms and legs.

So that's why some chromosomal abnormalities are more devastating than others. You're right that the genes on the extra chromosome are important.

But because we don't know which the deadly genes are, we can use chromosome size to predict how bad a chromosome abnormality will be. Except for the X chromosome, that is.

Amy Radermacher

An extra chromosome 21 leads to Down