How to sequence the human genome - Mark J. Kiel

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.