Other Genetic Principles

I was looking at a Wikipedia article on Chromosome 1. I was perusing the list of genes on Chromosome 1 and ran across these:

GLC1A: gene for glaucoma

HPC1: gene for prostate cancer

Do these genes have no other purpose than to trigger illness?

-A curious adult from Texas

March 16, 2007

I am happy to report that no, we don't have genes whose sole role in life is to cause disease. But it may seem this way, since we usually only hear about what a gene does when it seems to cause or be associated with a disease. The reason for this has to do with the way genes are discovered -- sometimes we only figure them out when something goes wrong!

First a reminder about what genes are and how they work. Humans have about 25,000 genes, which together we call the human genome.

Genes are made from DNA (or deoxyribonucleic acid). The basic building blocks of DNA are 4 chemicals called nucleotides. There are four nucleotides in DNA -- A, C, G, and T. Basically DNA is just big long strings of A's and T's and C's and G's. To make a human, each cell has about 3 billion of these letters in a certain order.

In people, all that DNA is divided into 23 chromosomes. And every now and then on the chromosome, a stretch of DNA makes up a gene (that's right, not all of our DNA makes genes, but that's a story for another day...). In turn, each gene has the instructions for a unique protein.

So each gene has the instructions for making a certain protein in certain cells at a certain time. It is through these proteins that the genome's plan is carried out.

You can think of genes and proteins kind of like a car. Your genes are like the instruction book and parts list of how to build a car. They contain all the information about what parts are needed when and where to make the car.

Proteins are the actual parts described in the instruction book (the car's genome). They are the wheels, lug nuts, windshield wipers, etc. Each protein, encoded by a gene, does a specialized job to make our bodies work like well-oiled machines.

A few years ago scientists sequenced all the DNA in the human genome. Basically they figured out the order of all the A's and T's and C's and G's.

This is incredibly useful information to have. But we can't usually just look at the sequence of a gene and know what it does for a living. So having all this information doesn't tell us what most of the genes do.

Scientists can sometimes figure out what a gene does by seeing what happens to the body when the gene is broken. A gene can become broken when there's a mistake in its DNA sequence, known as a genetic mutation. A mutation can be as seemingly harmless as a single mistake in the long DNA sequence of a gene. Maybe a "T" nucleotide showing up where a "C" was supposed be. This mistake can sometimes lead to a broken protein.

The broken protein, in turn, can cause all sorts of problems in the cells of the body. The damage done by a mutated gene can give us clues about how the gene (and its protein) works when it is functioning properly.

So to figure out what each gene does, scientists often have to look at what goes wrong when that gene is mutated. And as a result, this is often how the gene becomes known.

Such is the case for GLC1A and HPC-1, the genes you asked about. GLC1A was discovered when scientists realized that a broken version of it was associated with glaucoma. And a broken version of HPC-1 was found to be associated with prostate cancer.

Again, you can think of it kind of like your car. Unless you are a mechanic, you may not know what all the bits and pieces under the hood are for. As long as your car drives well, you are happy.

And for that matter, it is pretty hard to know what any individual part is doing when the car works well -- it just works! But it's a different story when one of the pieces stops working.

Take your car's alternator, for example. When your car works well, you may not know that your car even has an alternator, let alone what it does to help your car run properly!

But let's say that a mistake in your car's instruction book meant that a broken alternator was installed in your car. Your car would begin to lose power in its battery and the electrical systems would eventually fail.

Now an auto mechanic would take one look at your car and know the problem is with the alternator. But a scientist (who knows nothing about cars and had never heard of an alternator!) would look at your powerless car and have no idea what was wrong.

So s/he would sequence the car's genome (read the instruction book) and find the mutated, broken instructions by comparing it to an instruction book with the right instructions. The scientist would then say that this mutated section of the car's genome "encodes a gene for electrical system failure disease"!

As I said, this is one of the ways scientists discover genes too. But just because a gene is involved with a disease, we don't necessarily know what the unbroken gene does.

For example, the scientist looking at the mutation in your powerless car's instruction book has no idea what an alternator does. S/he only knows that when it is broken, the electrical system slowly fails. With more work, s/he will figure out what an alternator's normal function is.

This is where GLC1A and HPC-1 are right now. We don't know the role for the normal, healthy version of the GLC1A or the HPC-1 genes. Or how the mutated versions of these genes cause disease.

We just know that mutated GLC1A seems to result in glaucoma in some individuals. And that males with a mutated form HPC-1 have a higher incidence of prostate cancer. What GLC1A and HPC-1 do in healthy people, and why the mutated form of it is associated with glaucoma, is an active area of scientific research.

By Dr. Bronwyn MacInnis, Stanford University

Human genes are found on our 23 chromosomes.

A genome is like the instructions for making a car.