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如何对人类基因组进行测序 – 译学馆
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如何对人类基因组进行测序

How to sequence the human genome - Mark J. Kiel

TEDEd Lessons Worth Sharing
TED教育 课程价值在于分享
You’ve probably heard of the human genome,
你可能听说过人类基因组
the huge collection of genes inside each and every one of your cells.
即你身体内每个细胞的基因总和
You probably also know that we’ve sequenced the human genome,
你可能也知道我们已经完成了人类基因组的测序
but what does that actually mean?
但那到底是什么意思呢?
How do you sequence someone’s genome?
怎样对某人的基因组进行测序呢?
Let’s back up a bit.
让我们来补充一下背景知识
What is a genome?
什么是一个基因组?
well, a genome is all the genes
其实 一个基因组就是所有的基因
plus some extra that make up an organism.
加一些组成有机体的额外成分
Genes are made up of DNA,
基因由DNA组成
and DNA is made up of long, paired strands
然后DNA由长长的两条成对
of A’s, T’s, C’s, and G’s.
包含A T C G的单链构成
Your genome is the code that your cells use to know how to behave.
你的基因组是指导你的细胞行为的编码
Cells interacting together make tissues.
细胞在一起相互作用形成组织
Tissues cooperating with each other make organs.
组织间相互协作构成器官
Organs cooperating with each other make an organism, you!
器官间相互协作构成有机体 你就是一个有机体!
So you are who you are
所以在很大程度上
in large part because of your genome.
你的基因组让你成为了你自己
The first human genome was sequenced ten years ago
十年前第一个人类基因组被测序完成
and was no easy task.
这可不是个简单的任务
It took two decades to complete,
这次测序经过二十年才完成
required the effort of hundreds of scientists across dozens of countries,
需要几十个国家的上百位科学家们共同努力
and cost over three billion dollars.
并且耗资超过30亿美元
But some day very soon,
但在不久的将来
it will be possible to know the sequence of letters
我们几分钟就可以知道
that make up your own personal genome all in a matter of minutes
组成我们个人基因组的字母顺序
and for less than the cost of a pretty nice birthday present.
并且成本比一个很棒的生日礼物更少
How is that possible?
这是怎么做到的呢?
Let’s take a closer look.
让我们来仔细瞧瞧
Knowing the sequence of the billions of letters
获知数十亿组成你基因组的字母顺序
that make up your genome is the goal of genome sequencing.
是基因组测序的目标
A genome is both really, really big
一个基因组真的非常 非常大
and very, very small.
并且非常 非常小
The individual letters of DNA,
DNA的单个字母
the A’s, T’s, G’s, and C’s,
那些A T G和C
are only eight or ten atoms wide,
只有八到十个原子宽
and they’re all packed together into a clump,
它们全部一起组装成一个团簇
like a ball of yarn.
像一个毛线球
So, to get all that information out of that tiny space,
因此 想要从这么小的空间中获取所有信息
scientists first have to break the long string of DNA
科学家们首先必须将长链DNA
down into smaller pieces.
分解成更小的片段
Each of these pieces is then separated in space
接着每个片段在空间上分开
and sequenced individually,
然后分别测序
but how?
但是怎么测序呢?
It’s helpful to remember that DNA binds to other DNA
要记住如果序列彼此不能配对
if the sequences are the exact opposite of each other.
这个DNA就会结合其他DNA
A’s bind to T’s, and T’s bind to A’s.
A结合T 并且T结合A
G’s bind to C’s, and C’s to G’s.
G结合C 并且C结合G
If the A-T-G-C sequence of two pieces of DNA,
如果两个DNA片段的ATGC序列
are exact opposites
精确的配对
they stick together.
他们就会结合在一起
Because the genome pieces are so very small,
因为基因组片段非常微小
we need some way to increase the signal
我们需要一些方法来增加
we can detect from each of the individual letters.
从每个单独字母中探测到的信号
In the most common method,
在最常见的方法中
scientists use enzymes to make
科学家们用酶将DNA双链断裂
thousands of copies of each genome piece.
成千上万的基因组片段
So, we now have thousands of replicas
因此 我们现在有成千上万的
of each of the genome pieces,
基因组片段的复制品
all with the same sequence of A’s, T’s, G’s, and C’s.
所有的这些片段都有相同的A T G C序列
But we have to read them all somehow.
但我们必须以某种方式全数阅读它们
To do this, we need to make a batch
为此 我们得做一批
of special letters, each with a distinct color.
每个都拥有明显颜色的特殊字母
A mixture of these special colored letters and enzymes
一种这些上色的特殊字母和酶的混合物
are then added to the genome we’re trying to read.
稍后被加入到我们试图阅读的基因组中
At each spot on the genome,
在基因组中的每个位点上
one of the special letters binds to its opposite letter,
特殊字母中的一个结合为它的对应字母
so we now have a double-stranded piece of DNA
因此我们现在得到一段在每个字母上
with a colorful spot at each letter.
都带有彩色位点的双链DNA片段
Scientists then take pictures of each snippet of genome.
然后科学家把每个基因组片段拍照
Seeing the order of the colors allows us to read the sequence.
看颜色的顺序就让我们可以阅读序列
The sequences of each of these millions of pieces of DNA
这些数百万的DNA片段序列
are stitched together using computer programs
使用电脑程序拼接在一起
to create a complete sequence of the entire genome.
来创建一个完整基因组的全部序列
This isn’t the only way to
这不是唯一的方法
read the letter sequences of pieces of DNA,
去阅读DNA片段的字母序列
but it’s one of the most common.
但是最常见的方法之一
Of course, just reading the letters in the genome
当然 只阅读基因组里的字母序列
doesn’t tell us much.
并没有什么用
It’s kind of like looking through a book
这有点儿像翻一本
written in a language you don’t speak.
用一种你不懂的语言写的书
You can recognize all the letters
你能够认出所有字母
but still have no idea what’s going on.
但仍然不知道是怎么回事
So, the next step is to decipher
所以 下一步就是破译
what the sequence means,
这个序列意味着什么
how your genome and my genome are different.
我们每个人基因组间的差异
Interpreting the genes of the genome
解译基因组的基因怎样工作
is the part scientists are still working on.
是科学家们仍在努力研究的事情
While not every difference is consequential,
并非每一个基因差异都能引起表型差异
the sum of these differences is responsible for differences in
但这些基因差异的集合可以导致表型差异 比如
how we look, what we like, how we act,
我们的长相如何 喜好如何 行为如何
and even how likely we are to get sick
甚至我们患病的可能性如何
or respond to specific medicines.
或者对特定药物的反应如何
Better understanding of how disparities between our genomes
更好地理解我们基因组之间的差异
account for these differences is sure to change the way we think
如何导致这些表型差异必然会改变我们的思维方式
not only about how doctors treat their patients,
不仅仅关于医生如何对待病人
but also how we treat each other.
而且也关于我们如何对待彼此

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人类基因组测序技术的简单科普

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