Human genome more variable than previously thought

news@nature.com ^ | 22 November 2006 | Helen Pearson

[neverdem]

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Published online: 22 November 2006; | doi:10.1038/news061120-9

Human genome more variable than previously thought

Surprisingly large segments of DNA found to differ from person to person.

Helen Pearson

How alike are you and me? About 99.5%Getty

Nearly six years after the sequence of the human genome was sketched out, one might assume that researchers had worked out what all that DNA means. But a new investigation has left them wondering just how similar one person's genome is to another's.

Geneticists have generally assumed that your string of DNA 'letters' is 99.9% identical to that of your neighbour's, with differences in the odd individual letter. These differences make each person genetically unique — influencing everything from appearance and personality to susceptibility to disease.

But hold on, say the authors of a new study published in Nature¹. They have identified surprisingly large chunks of the genome that can differ dramatically from one person to the next. "Everyone has a unique pattern," says one of the lead authors, Matthew Hurles at the Wellcome Trust Sanger Institute in Cambridge, UK.

The differences in question - made up of stretches of DNA that span tens to hundreds of thousands of chemical letters — are called 'copy-number variants', or CNVs. Within a given stretch of DNA, one person may carry one copy of a DNA segment, another may have two, three or more. The region might be completely absent from a third person's genome. And sometimes the segments are shuffled up in different ways.

These variable regions received short shrift for many years. When the human genome sequence was pieced together, they were largely glossed over, because researchers were focused on finding one overarching reference sequence — and because the repetitive nature of the segments makes them hard to sequence. "It was swept under the rug," says Michael Wigler who is also mapping CNVs at Cold Spring Harbor Laboratory, New York.

All change

The new study, led by Hurles and Stephen Scherer of the Hospital for Sick Children in Toronto, Canada, and their colleagues is the most detailed attempt to find how CNVs are scattered across the whole human genome. To do this, they compared genome chunks from 270 people of European, African or Asian ancestry.

Same but different

3,080 million 'letters' of DNA in the human genome

22,205 genes, by one recent estimate

10 million single-letter changes (SNPs) — that's only 0.3% of the genome

1,447 copy-number variants, covering a surprisingly large 12% of the genome

About 99.5% similarity between two random people's DNA

They found nearly 1,500 such regions, taking up some 12% of the human genome. That doesn't mean that your DNA is 12% different from mine (or 88% similar), because any two people's DNA will differ at only a handful of these spots.

According to the team's back-of-the-envelope calculations, one person's DNA is probably 99.5% similar to their neighbour's. Or a bit less. "I've tried to do the calculation and it's very complicated," says Hurles. "It all depends on how you do the accounting."

The answer is also unclear because researchers think that there are many more variable blocks of sequence that are 10,000 or 1,000 letters long and were excluded from the current study. Because of limits with their methods, the new map mainly identified variable chunks larger than 50,000 letters long.

Many of these CNVs are thought to be important in our biology. The team found that 10% of human genes are spanned by these regions, meaning that they might be doubled, deleted or otherwise jumbled in a way that could help to determine whether and when we develop diseases.

CNVs have already been linked with susceptibility to Alzheimer's disease, kidney disease and HIV, among others, and the new map will help researchers to make connections to other conditions. "There's a general expectation that these things are quite influential," Wigler says.

Maps upon maps

The new map adds to a whole library of genetic cartography that already points out other landmarks in the human genome. A lot of attention has focused on mapping the places where single letters vary between individuals (single-nucleotide polymorphisms, or SNPs). Other researchers are identifying hard-to-spot regions where a segment can be flipped around so it runs backwards.

But there is plenty more for geneticists to navigate and undoubtedly more maps to come. Some will reveal the smaller regions of variation excluded from Hurle's map. Other projects are attempting to mark every single sequence that does something biologically useful, such as making proteins or packaging up DNA into chromosomes.

The precise degree to which each person's DNA differs from another may not become clear until geneticists devise a way to read through the entire genome of many different people and compare them all in detail, something that is far too expensive and time consuming today but may become possible with the advent of faster, cheaper sequencing machines.

Scherer and his team have already lined up the only two complete human genome sequences produced by the publicly funded Human Genome Project and the private company Celera. They identified both single-letter changes and small and large regions of variation and report their results in Nature Genetics².

Visit our newsblog to read and post comments about this story.

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References

1. Redon R., et al. Nature, 444. 444 - 454 (2006). | Article |
2. Khaja R., et al. Nature Genetics, advance online publication doi:10.1038/ng1921 (2006).

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Story from news@nature.com:
http://news.nature.com//news/2006/061120/061120-9.html

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[neverdem]

Global variation in copy number in the human genome Nature's article will have an impact.

Genetic breakthrough that reveals the differences between humans

[SWAMPSNIPER]

"Geneticists have generally assumed".

---

Assumptions are often misleading.

[taxed2death]

Geneticists have generally assumed...................



says it all.

[Don Corleone]

Geneticists have generally assumed that your string of DNA 'letters' is 99.9% identical to that of your neighbour's, with differences in the odd individual letter

Viva le differance.

[neverdem]

Been posted a couple of times already. :-)

Not this article from news@nature. Since it blows Mendelian genetics out of the water, it can't be posted enough. Did any link the actual article from Nature, i.e. the first link in comment# 1?

[Albertafriend]

"Since it blows Mendelian genetics out of the water..."

Can you please explain what this means? I have been tutoring a student in science and her course includes a section on DNA and how characteristics are passed to offspring. I find the topic very interesting but I don't fully understand this myself so perhaps you could help me out a bit.

[mountainlyons]

Atheists sure push DNA, homosexuality and evilution all from assumptions.

[neverdem]

Can you please explain what this means?

Can I explain what I took as a course for a semester in college decades ago? I don't think so. It explained inherited characteristics such as blue eyes or red hair by getting a copy of a recessive gene from each parent. It's a complicated subject. Perform a search on the term Mendelian Genetics. Here's one link that seems OK. Mendel's First Law of Genetics

[neverdem]

Atheists sure push DNA, homosexuality and evilution all from assumptions.

Tell that to Dr. Francis Collins, head of the Human Genome Project, and the author of "The Language of God: A Scientist Presents Evidence for Belief."

[mountainlyons]

I like Dr. Hugh Ross and his Reasons to believe website. There are many sides to the evidence from research but I find the left the most stubborn. It really bothers me to talk to someone that has an argument for something and will not even acknowledge any merit the others. I find the DNA studies interesting but some of the conclusions are really out there.

[Wacka]

It does NOT blow Mendelian Genetics out of the water.
It just means there is more variability than thought before.
Besides a lot of the "Human Genome Sequence" was taken from a group of people in Buffalo , NY.
DNA samples were taken from a group of people and pooled. This was then used in one of the two methods used to sequence the genome. The scientist who collected the DNA worked at Roswell Park Memorial Institute in Buffalo. The DNA was pooled, so no one race or ethnic group's traits were considered as the "standard".

[neverdem]

It just means there is more variability than thought before.

That's quite an understatement.

[SuziQ]

Doesn't surprise me. After all, we are "fearfully, wonderfully made".

[neverdem]

Red Wine Ingredient Increases Endurance, Study Shows

Midwest town sees return of old disease

FReepmail me if you want on or off my health and science ping list.

Your posting privilege has been suspended until 2006-11-23 01:48:11

Reason:
3 days off for copyright violation.
http://www.freerepublic.com/focus/f-news/1741331/posts

This thread has been pulled.

Pulled on 11/19/2006 8:46:07 PM EST by Admin Moderator, reason:

No link.

Don't forget the URL, or you can get suspended.

[PGalt]

Fascinating. Thanks the post/links. Thanks to all contributors.

[Jedi Master Pikachu]

Already went through posting opinions on this, here: http://www.freerepublic.com/focus/f-news/1743024/posts . Interestingly, this thread seems more in line and conducive with point, than the other one.

[Jedi Master Pikachu]

Agree that people should be respectful, and at least listen and know what other people believe in terms of origins, and the scientific evidence used to back it up. Disagree with Mr. Ross, though.

[Leftism is Mentally Deranged]

I guess all that scientists are admitting that they really know only a very small part of all that there is to know.

[neverdem]

Thanks for the link.