
A Mothers's Blood Reveals Entire Genome of Child  - J3L2404
http://www.cosmosmagazine.com/news/3908/mums-blood-test-reveals-genome-foetus
======
carbocation
> "Foetal DNA makes up about 10% of a pregnant woman's blood plasma." <\- I'd
> be quite surprised to learn that DNA makes up 10% of anyone's plasma, so I
> think they're saying that 10% of the DNA isolated from plasma is found to be
> fetal.

> "The latest research isolated foetal genetic signatures in the floating DNA,
> _then compared its characteristics against the genetic maps of the mother
> and father_. That way, scientists were able to construct a genome-wide
> genetic map of the foetus, which they could then scan for variations and
> mutations."

Now I'm interested to read more. The article can be found behind the following
paywall: <http://stm.sciencemag.org/content/2/61/61ra91.abstract> .

 _Update_ : OK, I was a bit confused by the DNA extraction process. From what
I can tell, they only took DNA from the parents once, at ~12 weeks gestation.
They then GWASsed them and found sites where the fetus would be an _obligate
heterozygote_ because the mother was homozygous for one allele while the
father was homozygous for another. (So if mom is AA and dad is GG, the fetus
must be AG, assuming no point mutation occurs there.)

But if the blood is only drawn once, 10% of the maternal DNA will be fetal
DNA, so how are they confidently calling sites as homozygous in the mother? I
suppose this makes sense if Birdseed is robust to 5% error in the data, and if
so this is quite clever. (5% because 10% of the DNA is fetal, and at the
obligate het sites half of that 10% will be maternal so only 5% total will be
of paternal origin.)

Now, their method is for high-depth whole-genome sequencing, which is still
very expensive, but there's no reason they couldn't use targeted sequencing
with this approach (they address this in the discussion). That would allow for
a potentially inexpensive test for inherited genetic disorders without
invading the fetal privileged space (which is what we currently do, and which
is high-risk).

~~~
Estragon
The hard part is figuring out the maternally inherited foetal DNA, because
it's already present in the mother's bloodstream. For features which are
present in the mother but not the father, it's fairly easy with the data they
have. For vice versa, it's probably not going to be possible for some time.

~~~
carbocation
Agreed, mostly, at least from first principles. The enrichment will be very
modest. On average for any given chromosome, 45% of DNA in the mother's blood
should be maternal DNA from one chromosomal copy or the other. This gets us to
90%.

The remaining 10% is split between one paternal copy and one maternal copy.

This means that--if we ignore other differences such as fragment length--
you're potentially trying to label the chromosomal copy that comprises 50% of
DNA as the one inherited by the fetus, versus the one comprising 45% of DNA as
the one not inherited by the fetus. That's a very small enrichment.

Now, because of the length differences that they identified, they may be able
to vastly enrich for fetal DNA (or precipitate out maternal DNA), obviating
this problem.

------
gojomo
People may also retain full cells from their mothers (or in extreme chimeral
cases, 'vanished twins') through their whole life:

[http://www.nytimes.com/2005/05/10/health/10bloo.html?_r=1...](http://www.nytimes.com/2005/05/10/health/10bloo.html?_r=1&pagewanted=all)

From the article:

 _Another route to chimerism is through the cells that routinely pass from a
mother to fetus and remain there for life.

Dr. Ann Reed, chairwoman of rheumatology research at the Mayo Clinic, who uses
sensitive DNA tests to look for chimerism, finds that about 50 to 70 percent
of healthy people are chimeras. The more scientists look for chimerism, the
more they find it. It seemed not to exist in the past, she said, because no
one was explicitly looking for small amounts of foreign cells in people's
bodies._

Further, experiments in mice show that stem cells from a fetus can take up
residence in the mother's body, possibly indefinitely _and_ granting benefits:

<http://www.vetscite.org/publish/items/002393/index.html>

Taken all together, these results suggests a woman might have persistent
chimeric cells from any or all of the following, if including all remote
possibilities:

• her own mother

• a 'vanished twin'

• a grandmother or earlier matrilineal ancestor (if those cells persisted in
the mother and then also transfered to the fetus)

• older siblings (if those cells persisted in the common mother and then also
transferred to the later fetus)

• her own children

• and of course, any donors from which the woman receives blood or tissue
during a medical procedure

------
Dove
There is a pregnancy condition called PUPPP -- itchy hives. I don't have a
reference to the study on hand, but it is known that most women who suffer
from PUPPP give birth to boys, and that male DNA is present in the hives. One
theory about it goes that male DNA is a skin irritant.

~~~
spitfire
You're saying men are an irritant? I'll buy that.

------
kevinpet
Bad science journalist draws conclusions not stated in the research reported
upon. It's clear to me that scanning for DNA fragments cannot tell you
anything about chromosome abnormalities, so I doubt the researchers said any
such thing.

Thus, this research is completely useless to anyone who would choose to screen
for the most common birth defects (not just sort of useless -- if you are
doing CVS or amnio, you have a cleaner source of DNA).

This technique seems only really useful for people who want to screen for
specific recessive diseases like tay-sachs or sickle cell, and don't want to
do a more invasive test.

~~~
carbocation
> It's clear to me that scanning for DNA fragments cannot tell you anything
> about chromosome abnormalities, so I doubt the researchers said any such
> thing.

It's not at all clear to me; why would you think this?

~~~
kevinpet
To take trisomy 21 as an example (Down's syndrome cause), this means the fetus
has three copies of chromosome 21. After a CVS or amnio, the lab will look at
the cells under the microscope and look for two copies of each chromosome. If
they find three instead, that's a chromosome abnormality. If you break open
the cells and end up with DNA fragments floating around, it's possible to
sequence the DNA but there's not any information that can tell you whether a
cell had an extra copy of a chromosome. It's like asking whether the apples to
make a cup of juice were all packed in the same box or multiple boxes.

Apparently this same researcher _does_ have a down syndrome test, but it is
based on measuring RNA ratios and does not seem to rely on sequencing the
fetus's DNA at all.

[http://www.nytimes.com/2008/10/07/health/research/07down.htm...](http://www.nytimes.com/2008/10/07/health/research/07down.html?_r=1&pagewanted=2)

So I am now confused as to what is being reported in this story. Is this using
DNA or fetal RNA?

~~~
carbocation
Glad I asked! I was thinking about chromosomal rearrangements, which would be
detectable using this method, but I agree with your point about
nondisjunction.

------
tocomment
How does DNA get into the bloodstream? It shouldnt be getting out of the
nucleus let alone the cell membrane and beyond that there's that whole
placenta thing.

This sounds bogus to me.

~~~
carbocation
Biology is not quite as clean as you seem to think it is.

------
funthree
By the time a mother has had a few kids, her blood has held all of the DNA in
the family.

I found the most striking revelation for me was that _my_ DNA will be floating
throughout my wife's body. That seems a bit weird... for her

~~~
Estragon

      _my_ DNA will be floating throughout my wife's body
    

Strictly speaking, only copies of half of your DNA.

~~~
sp332
Each time is half, but it's not always the same half. I think it's a 50/50
chance each time, so after 2 it's about 75%, 3 is about 88%, etc.

~~~
carbocation
I don't think they're claiming that this stuff sticks around in any
significant quantity after the fetus is delivered.

~~~
sp332
funthree said _By the time a mother has had a few kids, her blood has held all
of the DNA in the family._ and that's mostly true :-)

~~~
carbocation
Yes, agreed.

