You’ve probably heard of the human genome, the huge collection of genes inside each and every one of your cells. You probably also know that we’ve sequenced the human genome, but what does that actually mean? How do you sequence someone’s genome? Let’s back up a bit. What is a genome? Well, a genome is all the genes plus some extra that make up an organism. Genes are made up of DNA, and DNA is made up of long, paired strands of A’s, T’s, C’s, and G’s. Your genome is the code that your cells use to know how to behave. Cells interacting together make tissues. Tissues cooperating with each other make organs. Organs cooperating with each other make an organism, you! So, you are who you are in large part because of your genome. The first human genome was sequenced ten years ago and was no easy task. It took two decades to complete, required the effort of hundreds of scientists across dozens of countries, and cost over three billion dollars. But some day very soon, it will be possible to know the sequence of letters that make up your own personal genome all in a matter of minutes and for less than the cost of a pretty nice birthday present. How is that possible? Let’s take a closer look. Knowing the sequence of the billions of letters that make up your genome is the goal of genome sequencing. A genome is both really, really big and very, very small. The individual letters of DNA, the A’s, T’s, G’s, and C’s, are only eight or ten atoms wide, and they’re all packed together into a clump, like a ball of yarn. So, to get all that information out of that tiny space, scientists first have to break the long string of DNA down into smaller pieces. Each of these pieces is then separated in space and sequenced individually, but how? It’s helpful to remember that DNA binds to other DNA if the sequences are the exact opposite of each other. A’s bind to T’s, and T’s bind to A’s. G’s bind to C’s, and C’s to G’s. If the A-T-G-C sequence of two pieces of DNA are exact opposites, they stick together. Because the genome pieces are so very small, we need some way to increase the signal we can detect from each of the individual letters. In the most common method, scientists use enzymes to make thousands of copies of each genome piece. So, we now have thousands of replicas of each of the genome pieces, all with the same sequence of A’s, T’s, G’s, and C’s. But we have to read them all somehow. To do this, we need to make a batch of special letters, each with a distinct color. A mixture of these special colored letters and enzymes are then added to the genome we’re trying to read. At each spot on the genome, one of the special letters binds to its opposite letter, so we now have a double-stranded piece of DNA with a colorful spot at each letter. Scientists then take pictures of each snippet of genome. Seeing the order of the colors allows us to read the sequence. The sequences of each of these millions of pieces of DNA are stitched together using computer programs to create a complete sequence of the entire genome. This isn’t the only way to read the letter sequences of pieces of DNA, but it’s one of the most common. Of course, just reading the letters in the genome doesn’t tell us much. It’s kind of like looking through a book written in a language you don’t speak. You can recognize all the letters but still have no idea what’s going on. So, the next step is to decipher what the sequence means, how your genome and my genome are different. Interpreting the genes of the genome is the part scientists are still working on. While not every difference is consequential, the sum of these differences is responsible for differences in how we look, what we like, how we act, and even how likely we are to get sick or respond to specific medicines. Better understanding of how disparities between our genomes account for these differences is sure to change the way we think not only about how doctors treat their patients, but also how we treat each other.