Thoughts on the case. Setting up familial DNA databases

[Robittybob1]

Knowing whether their children were truly theirs has always posed a problem for men. That's why women were locked up in harems and guarded by eunuchs, for example.

There has been controversy about hospitals keeping new born heel prick samples beyond the official five year guideline in the UK. There have been suspicions that a national DNA database was being created without people's knowledge or consent.
https://www.telegraph.co.uk/news/health/7756320/DNA-database-created-from-babies-blood-samples.html

I assume that the British police got a court order to obtain Madeleine McCann's heel prick, because they sent it to the FSS to be checked against the sample of her DNA taken from her pillowcase.

They get permission to collect the sample.  In the US up to 29 diseases are tested for.
https://youtu.be/wSCXAKbM1mQ  here is how the collection is performed.

[misty]

I'm in favour of a permanent DNA database containing the profile of every baby (at time of birth), born in this country at least.  In that sense there could be no discrimination between criminals & non-criminals with regard to retention of data. The data could also be used for recording blood transfusions & bone marrow transplants, as the latter procedure alters the recipient's DNA permanently to include the donor's DNA. For LCN DNA profiling in a criminal case, that could result in erroneous evidence.

[Robittybob1]

I'm in favour of a permanent DNA database containing the profile of every baby (at time of birth), born in this country at least.  In that sense there could be no discrimination between criminals & non-criminals with regard to retention of data. The data could also be used for recording blood transfusions & bone marrow transplants, as the latter procedure alters the recipient's DNA permanently to include the donor's DNA. For LCN DNA profiling in a criminal case, that could result in erroneous evidence.

I wonder what the cost of doing that would be.  I will check up how one's DNA profile is changed by a bone marrow transplant. You could be right but I have never heard of that till now.

"After the treatments, stem cells are transplanted intravenously in a process called hematopoietic [blood making] stem cell transplantation (HSCT). Since blood cells are produced in the bone marrow, the blood of a recipient of an allogenic bone marrow transplant will have the donor's DNA."
https://gizmodo.com/during-a-transplant-does-the-donor-s-dna-integrate-into-1557455349

[misty]

https://www.watersheddna.com/blog-and-news/stemcelltransplantgedmatch


October 29, 2017
DNA Testing After a Stem Cell Transplant: a Fascinating Case
General Information
When you have an allogeneic bone marrow or stem cell transplant, the blood-producing cells in your bone marrow are killed off by radiation or chemotherapy and then replaced with functioning cells from another person. The technical term for this process is allogeneic hematopoietic cell transplantation.

In allogeneic transplants, DNA from your “donor” (the person donating the replacement cells to you) travels along inside the cells that get transplanted, and you become a chimera at that point. (A transplant with your own cells is called an autologous ["self proportion"] transplant and does not affect your DNA makeup). After a donor’s cell take root in your body, you now have two separate sets of DNA represented in your tissues. Which results come back when you have a DNA test after your transplant depends on which cells get tested. The complexity of this situation makes it easy to understand how this has become the storyline of more than one crime scene investigation show on TV!

This type of acquired chimerism is distinct from the rare form chimerism present at birth -- congenital chimerism. Congenital chimerism happens when someone is born already having two distinct sets of DNA. It is thought to be caused by fraternal twin embryos joining early on in pregnancy to form one person. In a way, it is the inverse of identical twinning, when one egg splits into two. Congenital chimerism has only been documented in a few cases including the well-publicized case of Lydia Fairchild and one case I was involved in professionally just a few years ago, described in this Time magazine article here.

Acquired chimerism is growing more and more common with stem cell transplants being an available treatment for a number of conditions like lymphoma, leukemia, and sickle cell disease. Some hypothesize that the rise in fertility treatments for pregnancy conception might also be increasing the number of individuals born with congenital chimerism (due to increased twinning rates at conception); however, this theory has yet to be studied and tested.

Doing DNA testing on people who have already had a stem cell or bone marrow transplant can get tricky. Because there is interaction between the blood stream and types of cells lining the cheeks and because cells from your blood stream can get into your saliva, we actually can find both sets of DNA when we do a test on saliva or a cheek swab. Per multiple testing companies, this often causes the test to result in “failure” for many people who have been through a transplant.

Here's what 23andMe wrote in response to a customer question on the topic:

"If you have received a bone marrow transplant, we cannot recommend that you use the 23andMe® Personal Genetic Service (Ancestry Service or Health & Ancestry Service).

The saliva sample required to receive the 23andMe Personal Genetic Service includes DNA from multiple cell sources, including epithelial cells from your cheeks and mouth and white blood cells from your saliva. As a bone marrow recipient, your blood cells will contain the DNA from your marrow donor, while your epithelial cells contain your own DNA. The combination of DNA sources frequently results in analysis failure. In the event that the analysis was successful, it still would be unclear whether the results were based on DNA from you or from your donor."

What I recently learned is that in some cases, the sample doesn’t fail! I had a gentleman ("Tom") reach out to me who had tested both prior to and after his stem cell transplant. When he took the raw data from his pre- and post-transplant DNA tests to the website GEDmatch.com and ran analysis of his DNA against other people in his family, the results were surprising. And yet, knowing the history of his transplant and who in his family was his donor, the results were not surprising. They actually made a lot of sense!

I am going to show you how this gentleman matched two people in his family along chromosome number 1, and I want you to guess which family member -- his sister or his son -- was his stem cell donor.

If you are new to learning about GEDmatch, this is going to be more challenging for you! But hang around and give it a try. You might be able to figure it out even if you’ve never used GEDmatch before.

Tom and his sister before the transplant

Screen Shot 2017-10-26 at 11.16.02 PM.png
Tom and his sister after the transplant

Screen Shot 2017-10-26 at 11.22.02 PM.png
Tom and his son before the transplant

Screen Shot 2017-10-26 at 11.25.02 PM.png
Tom and his son after the transplant

Screen Shot 2017-10-26 at 11.25.59 PM.png
Here's a key to understanding the color coding in GEDmatch:

Screen Shot 2017-10-26 at 11.16.15 PM.png
Did you figure it out?

Tom’s sister was his donor! So now Tom is a chimera, with some of the DNA he was born with and his own sister’s DNA present in some of his cells. All that we see in his raw data file now, however, is his sister's DNA.

Tom was happy to share his story but has a word of advice:

“
If I had one thing to tell people going through a transplant, it would be to have a DNA test done prior to the transplant for history’s sake.
If you wait until after a transplant and then try to do a DNA test like 23andMe or AncestryDNA, you might forever lose the opportunity to have a true reflection of the DNA you were born with. This also means you may lose out on the opportunity to explore how your DNA matches other people, including your children, siblings, and future generations.

[Eleanor]

The idea is to widen the scope of the database by including all families over a period of time.
In some cases they haven't got a body but evidence of the victim and perpetrator at a crime scene.  After a while there can be enough circumstantial evidence to produce a case.

I have never been wild about relying on DNA.  The best that they can mostly do is One in a Million.  What is that supposed to mean?  What about all of the Ones in all of the other Millions, and the chances of one of them living in the vicinity?

And then there is the perpetrator who doesn't leave any DNA, while some unfortunate, innocent person did.  How many of those are languishing in prison at the moment.

There is much more to the basic unreliability of DNA, but I don't have enough knowledge on the subject.

[Robittybob1]

I have never been wild about relying on DNA.  The best that they can mostly do is One in a Million.  What is that supposed to mean?  What about all of the Ones in all of the other Millions, and the chances of one of them living in the vicinity?

And then there is the perpetrator who doesn't leave any DNA, while some unfortunate, innocent person did.  How many of those are languishing in prison at the moment.

There is much more to the basic unreliability of DNA, but I don't have enough knowledge on the subject.

I have heard of 1 in billion recently.  I think there has to be more than just the DNA in most cases.

[Eleanor]

I have heard of 1 in billion recently.  I think there has to be more than just the DNA in most cases.

Of course there should be more, Rob, and often there is.  But not always.  The lack of an alibi can sometimes hang someone.

Just how many people in the world do have the same DNA?  And why?  No one seems to have addressed this.  It's no good telling me One in a Million, or even One in a Billion.  There is a Doubt however small.

[jassi]

I have heard of 1 in billion recently.  I think there has to be more than just the DNA in most cases.

Of course, but once you have identifiable DNA found in circumstances where it shouldn't be found, then you have the basis for further investigation.

[Eleanor]

Of course, but once you have identifiable DNA found in circumstances where it shouldn't be found, then you have the basis for further investigation.

But it wasn't found in The McCann Case.  Only bits and pieces of convoluted DNA.  But this was enough to hang The McCanns in the minds of some.

[jassi]

I think the McCann case is a good example of the weaknesses of DNA analysis, in that complex mixtures can be difficult, if not impossible to resolve.

[Robittybob1]

But it wasn't found in The McCann Case.  Only bits and pieces of convoluted DNA.  But this was enough to hang The McCanns in the minds of some.

It is how that evidence is presented.  The 15 markers found in the car sample was 15 out of 37  and the sample was mixed (3 or more persons).
If you say "it was inconclusive" (FSS), or it was "1 in a billion to have 15 out of the 19 markers for Madeleine" (like Goncalo Amaral) makes a huge difference.  Same result expressed in two different ways.

[Eleanor]

I think the McCann case is a good example of the weaknesses of DNA analysis, in that complex mixtures can be difficult, if not impossible to resolve.

It is indeed, Jassi.  But it bothers me that any sort of DNA however corrupted can be misunderstood.

I don't really understand The Heel Prick Test.  Why do they do it, and what do they do with it?  All of my children, some fifty odd years ago were subjected to this, and I didn't even know what they were doing.

Is The DNA of my children On Record?  And is it available for DNA Testing?

[jassi]

It is indeed, Jassi.  But it bothers me that any sort of DNA however corrupted can be misunderstood.

I don't really understand The Heel Prick Test.  Why do they do it, and what do they do with it?  All of my children, some fifty odd years ago were subjected to this, and I didn't even know what they were doing.

Is The DNA of my children On Record?  And is it available for DNA Testing?

They take to test for phenylketonuria and a thyroid disorder.
This is a national screening program and samples are stored for several years.
Provided that there is sufficient sample, other tests can be carried out if considered necessary.

[Eleanor]

It is how that evidence is presented.  The 15 markers found in the car sample was 15 out of 37  and the sample was mixed (3 or more persons).
If you say "it was inconclusive" (FSS), or it was "1 in a billion to have 15 out of the 19 markers for Madeleine" (like Goncalo Amaral) makes a huge difference.  Same result expressed in two different ways.

Not the same thing, Rob.  If that is your One in a Billion then Amaral was indeed totally ignorant of any understanding of DNA.

[Robittybob1]

It is indeed, Jassi.  But it bothers me that any sort of DNA however corrupted can be misunderstood.

I don't really understand The Heel Prick Test.  Why do they do it, and what do they do with it?  All of my children, some fifty odd years ago were subjected to this, and I didn't even know what they were doing.

Is The DNA of my children On Record?  And is it available for DNA Testing?

The way the heel prick samples are stored means that after that number of years  any DNA would have broken up and it would be unsuitable for DNA testing.

There are more conditions being analysed for today than in the past.  In the USA the report said up to 26 conditions can be checked for.