How to sequence the human genome - Mark J. Kiel

如何定序人類基因組? – 馬克‧J‧基爾

譯者: Ya Hui Hung 審譯者: Philip Wong

You've probably heard of the human genome,

你可能聽說過人類基因組吧!

the huge collection of genes

完整的基因組

inside each and every one of your cells.

存在每個細胞內。

You probably also know

你也許知道

that we've sequenced the human genome,

我們已經完成了人類基因組定序，

but what does that actually mean?

但這有什麼意義呢?

How do you sequence someone's genome?

基因組要如何定序呢?

Let's back up a bit.

讓我們從頭講起。

What is a genome?

什麼是基因組?

Well, a genome is all the genes plus some extra

一個生物的基因組包括所有的基因

that make up an organism.

和一些額外的元素。

Genes are made up of DNA,

基因是由 DNA (脫氧核糖核酸) 組成，

and DNA is made up of long, paired strands

雙股螺旋的 DNA 基本單位是

of A's,

A (Adenine, 腺嘌呤)

T's,

T (Thymine, 胸腺嘧啶)

C's,

C (Cytosine, 胞嘧啶)

and G's.

G (Guanine, 鳥嘌呤)

Your genome is the code

基因組是

that your cells use to know how to behave.

指揮細胞運作的密碼。

Cells interacting together make tissues.

細胞的互動形成組織構造。

Tissues cooperating with each other make organs.

器官的產生來自組織間的合作。

Organs cooperating with each other

器官間的合作

make an organism,

演變成一個生物，

you!

就是你!

So, you are who you are

基因組是主宰個體差異

in large part because of your genome.

最大的元素之一。

The first human genome

十年前，史上第一

was sequenced ten years ago

人類基因組定序的完成

and was no easy task.

不是一件易事。

It took two decades to complete,

這工程花了二十年，

required the effort of hundreds of scientists

跨越幾十個國家

across dozens of countries,

動用了數百個科學家

and cost over three billion dollars.

和三十億元以上的成本。

But some day very soon,

但很快的，

it will be possible to know the sequence of letters

只要短短的幾分鐘

that make up your own personal genome

我們將能輕易的

all in a matter of minutes

得到個人的基因定序，

and for less than the cost

而費用將相當於

of a pretty nice birthday present.

一個不錯的生日禮物。

How is that possible?

這怎麼可能?

Let's take a closer look.

讓我們仔細看。

Knowing the sequence of the billions of letters

定序的目的

that make up your genome

是將數十億字母組成的

is the goal of genome sequencing.

基因組排列出來。

A genome is both really, really big

一個基因組

and very, very small.

可大可小。

The individual letters of DNA,

每個 DNA 字母

the A's, T's, G's, and C's,

A， T ，G，和 C

are only eight or ten atoms wide,

只有 八到十個原子大小，

and they're all packed together into a clump,

像毛線球

like a ball of yarn.

緊縮成一團。

So, to get all that information

要將濃縮的基因組

out of that tiny space,

解碼，

scientists first have to break

要先段式分解

the long string of DNA down into smaller pieces.

有如長鏈的 DNA 。

Each of these pieces is then separated in space

然後再將每片段

and sequenced individually,

分開定序。

but how?

這要如何辦到?

It's helpful to remember

記住了，

that DNA binds to other DNA

DNA 跟 DNA 的結合，

if the sequences are the exact opposite of each other.

序列是完全相反的。

A's bind to T's,

A 的配對是 T，

and T's bind to A's.

T 的配對是 A，

G's bind to C's,

G 的配對是 C，

and C's to G's.

C 的配對是 G。

If the A-T-G-C sequence of two pieces of DNA

如果兩段 DNA 的 A-T-G-C 的序列

are exact opposites,

完全相反，

they stick together.

它們會結合在一起。

Because the genome pieces

基因組的片段

are so very small,

數量很小，

we need some way to increase

所以需要有方法

the signal we can detect

增加 DNA 字母

from each of the individual letters.

定序信號。

In the most common method,

是最普遍的方法

scientists use enzymes to make thousands of copies

是利用酶來拷貝

of each genome piece.

基因組的片段。

So, we now have thousands of replicas

製造成千上萬的

of each of the genome pieces,

複製品，

all with the same sequence

每個都有相同序列的

of A's, T's, G's, and C's.

A， T ，G，和 C。

But we have to read them all somehow.

這些要如何檢測?

To do this, we need to make

首先，需要製造

a batch of special letters,

一批特殊的 DNA 字母，

each with a distinct color.

每個有它獨特的顏色。

A mixture of these special colored letters and enzymes

先混合有顏色的 DNA 字母和酶

are then added to the genome

再加入要定序的

we're trying to read.

基因組。

At each spot on the genome,

有顏色的 DNA 字母

one of the special letters

和相對的 DNA 字母

binds to its opposite letter,

會結合。

so we now have a double-stranded piece of DNA

這樣雙股螺旋的 DNA

with a colorful spot at each letter.

每個位置都有一個顏色。

Scientists then take pictures

科學家可以記錄下

of each snippet of genome.

每個基因組片段。

Seeing the order of the colors

利用顏色的順序

allows us to read the sequence.

解讀基因組的序列。

The sequences of each

成千上萬

of these millions of pieces of DNA

基因組片段的序列

are stitched together using computer programs

輸入電腦

to create a complete sequence of the entire genome.

將能建造完整的基因組定序。

This isn't the only way

這不是唯一

to read the letter sequences of pieces of DNA,

解讀 DNA 序列的方法，

but it's one of the most common.

但是最普遍的方法之一。

Of course, just reading the letters in the genome

當然，只看懂基因組的字母

doesn't tell us much.

沒有什麼意義。

It's kind of like looking through a book

就有如

written in a language you don't speak.

文盲看書。

You can recognize all the letters

換句話說，

but still have no idea what's going on.

有看沒有懂。

So, the next step is to decipher

接下來，

what the sequence means,

要解碼，

how your genome and my genome are different.

來了解個人基因組的差異。

Interpreting the genes of the genome

科學家們仍在研究

is the part scientists are still working on.

如何解讀基因組內每個基因。

While not every difference is consequential,

雖然每個人的基因大同小異，

the sum of these differences

但累積起來，

is responsible for differences

這些小差異造就

in how we look,

我們不同的長相，

what we like,

喜好，

how we act,

行為，

and even how likely we are to get sick

甚至於對生病

or respond to specific medicines.

或藥物的敏感度。

Better understanding of how disparities

深入的了解

between our genomes

基因組的差異

account for these differences

和基因栓釋

is sure to change the way we think

將能改變我們的思維，

not only about how doctors treat their patients,

影響醫生給病人的醫療處方，

but also how we treat each other.

和我們的待人方式。