How to sequence the human genome - Mark J. Kiel

如何对人类基因组进行测序 - 马克.J.基尔

翻译人员: Tian Ye 校对人员: Yuanqing Edberg

You've probably heard of the human genome,

你大概听说过人类基因组，

the huge collection of genes

它是巨量的基因总和

inside each and every one of your cells.

在你的每一个细胞里都有一份。

You probably also know

你很可能也知道

that we've sequenced the human genome,

我们已经对人类基因组进行了测序，

but what does that actually mean?

但这到底是什么意思？

How do you sequence someone's genome?

怎样对一个人的基因组进行测序呢？

Let's back up a bit.

我们先讲点背景知识。

What is a genome?

什么是基因组？

Well, a genome is all the genes plus some extra

基因组，就是全部的基因再加上点别的

that make up an organism.

共同组成了有机体。

Genes are made up of DNA,

基因由DNA组成，

and DNA is made up of long, paired strands

而DNA是成对的长链，

of A's,

由A（腺嘌呤），

T's,

T（胸腺嘧啶），

C's,

C（胞嘧啶），

and G's.

和G（鸟嘌呤）组成。

Your genome is the code

你的基因组是一组代码，

that your cells use to know how to behave.

你的细胞要通过它来知道自己该做什么。

Cells interacting together make tissues.

细胞交织在一起成为组织，

Tissues cooperating with each other make organs.

不同的组织协调构成了器官，

Organs cooperating with each other

器官间协同工作

make an organism,

则形成了有机体，

you!

就是你！

So, you are who you are

所以，你之所以是你

in large part because of your genome.

很大程度上原因在于你的基因组。

The first human genome

第一个人类基因组测序

was sequenced ten years ago

完成于十年前，

and was no easy task.

非常艰难。

It took two decades to complete,

它花了20年才完成，

required the effort of hundreds of scientists

需要来自几十个国家的

across dozens of countries,

几百位科学家付出了辛劳，

and cost over three billion dollars.

而且费用超过30亿美元。

But some day very soon,

但不久的一天，

it will be possible to know the sequence of letters

搞清组成你这个人的基因组的

that make up your own personal genome

字母排列将成为可能，

all in a matter of minutes

只要几分钟，

and for less than the cost

费用还不及

of a pretty nice birthday present.

一份不错的生日礼物贵。

How is that possible?

这怎么可能呢？

Let's take a closer look.

让我来解释一下。

Knowing the sequence of the billions of letters

搞清组成你的基因组的

that make up your genome

几十亿个字母排列，

is the goal of genome sequencing.

是基因组测序的目标。

A genome is both really, really big

基因组既很大很大，

and very, very small.

又很小很小。

The individual letters of DNA,

DNA的每个字母，

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

就是A、T、G、C，

are only eight or ten atoms wide,

宽度只有8到10个原子，

and they're all packed together into a clump,

而他们全部缠在一起成为一团，

like a ball of yarn.

像一团毛线。

So, to get all that information

所以，要从这么小的地方

out of that tiny space,

获取所有这些信息，

scientists first have to break

科学家首先要把

the long string of DNA down into smaller pieces.

DNA的长链打断为许多短链。

Each of these pieces is then separated in space

然后把每一段分离出来

and sequenced individually,

单独测序，

but how?

怎么测？

It's helpful to remember

这样想一下会更容易理解：

that DNA binds to other DNA

DNA会和其它DNA交合

if the sequences are the exact opposite of each other.

如果彼此的序列刚好互补的话。

A's bind to T's,

A配T，

and T's bind to A's.

T配A。

G's bind to C's,

G配C，

and C's to G's.

C配G。

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

如果两片DNA的序列ATGC

are exact opposites,

刚好互补

they stick together.

它们就会结合在一起。

Because the genome pieces

因为基因组片段

are so very small,

非常小，

we need some way to increase

我们需要某些办法

the signal we can detect

来放大信号，这样才能检测到

from each of the individual letters.

每个字母是什么。

In the most common method,

科学家最常用的方法，

scientists use enzymes to make thousands of copies

是用酶来合成几千份

of each genome piece.

基因副本

So, we now have thousands of replicas

这样我们就有了每一个基因组

of each of the genome pieces,

几千份复制品，

all with the same sequence

全部都有一样的

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

ATGC序列，

But we have to read them all somehow.

但我们还得把全部的序列读出来。

To do this, we need to make

为了做到这一点，我们需要

a batch of special letters,

制作一批特别字母，

each with a distinct color.

每种都有特殊的颜色。

A mixture of these special colored letters and enzymes

把这些带颜色标记的字母和酶混合在一起，

are then added to the genome

再加入到

we're trying to read.

我们试图阅读的基因组里

At each spot on the genome,

在基因组的每一个点上，

one of the special letters

有一个特殊字母

binds to its opposite letter,

和对应的字母结合，

so we now have a double-stranded piece of DNA

这样就有了一段双链DNA，

with a colorful spot at each letter.

并且在每个字母上都有颜色标记。

Scientists then take pictures

然后科学家

of each snippet of genome.

对每一小段基因组照相，

Seeing the order of the colors

看到了颜色的排列顺序，

allows us to read the sequence.

我们就可以读出序列。

The sequences of each

这样几百万条DNA片段

of these millions of pieces of DNA

的序列

are stitched together using computer programs

是由计算机程序拼接一起的

to create a complete sequence of the entire genome.

这样就得到了整个基因组的完整序列。

This isn't the only way

这并非读取DNA片段序列字母的

to read the letter sequences of pieces of DNA,

唯一方法

but it's one of the most common.

却是最常用的方法之一。

Of course, just reading the letters in the genome

当然，仅仅是读取了基因组中的字母

doesn't tell us much.

还远远不够。

It's kind of like looking through a book

就好像你在翻一本书，

written in a language you don't speak.

书中所用的语言你并不懂，

You can recognize all the letters

你能读出书里的每个字母，

but still have no idea what's going on.

却仍然不理解书里说什么。

So, the next step is to decipher

所以，下一步就是解码，

what the sequence means,

序列到底是什么意思，

how your genome and my genome are different.

为什么你的基因组和我的不一样。

Interpreting the genes of the genome

阐释基因组中的不同基因的功能，

is the part scientists are still working on.

是科学家正在进行的工作。

While not every difference is consequential,

虽然并不是每一处不同之处都意义重大，

the sum of these differences

但这些不同之处组合在一起

is responsible for differences

决定了人与人之间的不同。

in how we look,

它决定了我们怎么看，

what we like,

我们喜欢什么，

how we act,

我们如何反应，

and even how likely we are to get sick

甚至我们患上疾病的可能性，

or respond to specific medicines.

或是对特定药物的反应。

Better understanding of how disparities

更好地了解

between our genomes

我们各自的基因组有哪些差别，

account for these differences

认识到这些差别

is sure to change the way we think

必将改变我们的观念：

not only about how doctors treat their patients,

不光是医生应当如何治疗病人，

but also how we treat each other.

而且是我们该如何。