Starting from the beginning

A short primer on DNA technology

Us humans consist of about 30 trillion cells. And all those cells are made from the same blueprint, your DNA. This molecule, DNA,  contains all the information needed by the body to make everything that is you. The structure of the DNA helix was discovered in 1953, and we still have much to learn from it. Despite intense study, we still have not completely uncovered how everything works. We do, however, have a pretty good knowledge on how DNA is being used in the body. The DNA code itself stores information about how to build proteins, essential components for making the various tissues and other components in the body. This can be understood by reading the DNA sequence, which is the order of the four different kinds of bases that makes up the DNA molecule. The bases are Adenine, Thymine, Cytosine and Guanine. More commonly, we refer to them as A, T, C and G. By reading this code we have found genes that make proteins involved in our organ development, ability to speak, feel happiness and depression, and almost any other bodily function you can imagine.

We have only been able to peak at this DNA code for quite a short amount of time. In 2004 the sequence of the human genome was first published. This was made possible to a global effort of thousands of scientists, and many hundred million dollars worth of funding. Since then massive advancement has been made, and today we can sequence (meaning to determine the DNA code) a human genome for a fraction of the cost, in a few days. It is now possible to start looking into the very blueprint of our own bodies. And isn’t that just the most amazing thing, being able to read how you were made?

You are unique

And so is your DNA

The human DNA is made up of about 3 billion bases, A’s, T’s, C’s and G’s. These are divided into 46 chromosomes, and each chromosome has a sister, giving us 23 pairs. If we would look at all these letters, and compare the amongst ourselves, we wouldn’t find two people with the same identical code in the whole world, unless you happen to have an identical twin that is. However, most of our DNA is the same between us. The part of the DNA that codes for proteins, the genes, are mostly the same when we compare two people. And they have to be, any changes in these regions could potentially be problematic. However, most of our DNA does not encode for proteins. Only about 3 % of all our DNA are instructions in how to build proteins. The other 97 % are regulatory regions, regions that encode for building blocks other than proteins, and the biggest part of all we just don’t really know why it is there.

But looking at the sequence of the bases, all 3 billion of them, isn’t the only way we can use DNA to see how we as individuals are unique. In our genome, we have regions which differ, not only in sequence, but also in length, if we compare two people. Such regions are called length polymorphisms. The difference in length comes from the way these length polymorphisms are put together. They are made up of blocks of DNA, that is repeated several times. A repeating unit usually consists of 2-100 bases, and can be repeated between one and thousands of times. This makes regions very greatly in length if we compare two people. Let’s say we look at one of these regions, and we can see that the repeating region is 8 bases long, ATCGATCG. In person A, there is just two such repeating regions, making the total length of the region 16 bases long. When we look in person B, we might find four repeating units, making the region 32 bases long. By looking at several of these regions, we can make a profile of length of all the regions. And if we look at enough of these regions, and we only really need about 11-13 of them, we have enough information to be able to distinguish one person from another. This is the very basis of the genetic self-portraits we make here at Pixel Biology.

Seeing the difference

How to visualise your DNA

In order to make our genetic self portraits we look at 18 regions of your DNA which vary in length. This is done by first generating millions of copies of this region, by a technique called PCR (polymerase chain reaction). This is done so we have enough genetic material in order to take it to the next step. This next step is called gel electrophoresis, and is used to be able to differentiate DNA molecules by length. We load the DNA material from each of the regions into a gel made from agarose, a sugar extracted from sea weed. This looks very similar to a slab of agar-agar, or gelatine. We then apply a current, and since DNA is a charged molecule, it will travel through the gel. A long DNA fragment will go slowly, since the length of the molecule itself will make if harder for it to go through the structure of the gel. A shorter molecule will be able to go faster, and will therefor travel a longer distance in the same amount of time.

After a set amount of time, we stop the current and apply a special dye, that binds to the gel itself. This is needed to be able to see the DNA. This dye is fluorescent when placed under a UV light, so when we place the gel on a UV table, we are able to take an image, the very basis of your genetic self-portrait. Short fragments, which traveled faster, will be towards the bottom of the gel, and longer ones towards the top. We can determine the size of each DNA fragment by adding what is called a DNA ladder, a set of DNA fragments with known lengths. We add this ladder to the outside of the gel, on both sides.After we have taken the image, we apply the color scheme you selected and we send it of for print.

Digging deeper

Understanding everything in the image

Your genetic self portrait consists of 8 columns, with a number of bands in each column. The two outermost columns are used for the DNA ladder. These are DNA fragments of known length we add in order to be able to determine the size of each individual fragment. The shortest bands, on the bottom of the image, are 200 bases long, and the largest are 3000 bases. In columns 2-7 we have added the DNA from your sample. Each column contains the DNA from three different regions, which gives between 3-6 bands per column. The reason why a single marker can give two bands, is from the fact that our chromosomes comes in pairs. As an example, let’s imagine a single DNA marker from chromosome 11. We have two copies of chromosome 11, and we can call these copies 11-a and 11-b. If we were to look at the location of our marker region on each of these copies, we would see that sometimes they differ in length between themselves. So a region could be 400 bases long on 11-a and 1000 bases long on 11-b. Each one of those will show up as a band on the final gel. If they both have the same length, the will be on the exact same spot on the gel, and we will only see one band. Since we use a total of 18 markers for each genetic self-portrait, any given person would be able to see between 18 to 36 bands on their very own portrait.

This fact that we have two copies of each chromosome is also the basis for how we pass on our DNA to our children. Each gene we have in our DNA comes in two copies, one on each sister chromosome. When we pass on genetic material to our kids, we only give them one copy of that gene, only one of our chromosomes are inherited. This is also true for when we pass on the DNA which makes up the marker regions. In our previous example, only one copy of chromosome 11 will be passed on. If this was the copy that was 400 bases long, we will be able to see at least one copy being that length if we make another portrait of our child. It could be that the partner also passed on a 400 base long region, and in that case our child will only have a single band showing up for that region. By looking at all 18 regions we can puzzle together just which regions came from which parent.