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Cornella
03-23-2016, 02:59 AM
I was wondering whether having had a bone marrow transplant complicates ancestry tests. As I understand it, blood based tests will be affected and give the results of the BM donor, whereas saliva based tests will give your own results. Does anyone have any knowledge on this? Thanks.

DMXX
03-23-2016, 05:44 AM
Bone marrow (red) is the spongy tissue found within certain large bones in the body and is made up principally of haematopoietic stem cells. These are responsible for the production of red blood cells, white blood cells (wide variety of subtypes, general term leukocytes) and platelets.

The genetic information within a cell is located in the nucleus. Practically every cell in the body contains a nucleus, with the exception of red blood cells and platelets. The haematopoietic stem cells in bone marrow also have a nucleus.

Another important point to be considered here is all non-gonadal non-cancer cells within your body possess the exact same genetic blueprint in the nucleus. Everything from skin, white blood, nerve, muscle to gastrointestinal lining cells. As they deal with the body in its' entirety, we describe these as somatic cells (https://ghr.nlm.nih.gov/glossary=somaticcell).

A final point to consider is the material present in human saliva. Though overwhelmingly water (>99%), it also contains mucosally secreted antibodies (IgA), antimicrobial compounds (e.g. lactoferrin), enzymes (mainly salivary amylase), bacterial flora (hence the cause of plaques, cavities, gingivitis etc.) and... Human cells! These are chiefly either leukocytes (http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0765.1970.tb01835.x/abstract) or sloughed-off buccal epithelial cells (the lining of your inner mouth).

Returning to bone marrow replacement, there are two types of transplant;
1) Autologous; involves extracting fragments of healthy bone marrow from the patient and freezing them, destroying all their bone marrow (malignant and healthy tissue), then reinfusing the patient with their original healthy marrow (effectively a "self-owned reset")
2) Allogeneic; involves receiving healthy bone marrow from a different individual who matches the patient in terms of immunosignalling markers (referred to as the HLA type), destroying all their bone marrow (malignant and healthy tissue), then reinfusing the patient with their match's marrow

Tying the above together...
1) With an autologous transplant, neither blood nor saliva will be adversely compromised, as all the cell lines found in both are still fully derived from the patient/customer.
2) With an allogeneic transplant, things become trickier. Blood tests will produce the wrong result, as the leukocytes will be derived from the donor's stem cells. Saliva will be a mixed bag, as it'll contain both donor-derived leukocytes, or the patient's own buccal epithelial cells, which haven't changed (as epithelial cells don't derive from haematopoietic stem cells).

The solution with allogeneic transplant testees would be to either inform the testing laboratory of the situation when contributing saliva and see if they have techniques to isolate the epithelial cells and ignore the leukocytes (mechanical centrifugal separation might work, that is beyond my expertise), or, they can volunteer DNA from a non-haematopoietic derived somatic tissue (e.g. hair, skin).

Hope that's answered your question sufficiently!

[Edit]: Just seen this. Similar question asked to a trained biologist, near-identical answer as above (http://www.askabiologist.org.uk/answers/viewtopic.php?id=6352).

Gravetto-Danubian
03-23-2016, 05:48 AM
One minor comment - BM is mostly just fat, after childhood

DMXX
03-23-2016, 05:58 AM
One minor comment - BM is mostly just fat, after childhood

It's a bit more complicated than that; if all bone marrow after childhood was replaced with adipose tissue, most adolescents, adults and elderly individuals would have clinical myelosuppression (how else will the RBC's, platelets and WBC's be made? :D ).

G-D is correct that, over time, the proportion of "active" (red) bone marrow slowly shifts towards the "inactive fatty" (yellow) form. By peak adulthood, just over half of an average person's marrow will remain red. In the elderly phases of life, the proportion of red dwindles to become a minority. Here's an instructive article on the frank characteristics of bone marrow over time (http://emedicine.medscape.com/article/1968326-overview#a2).

As you've mentioned a post-childhood milestone and near-complete replacement with fat, is there any chance you may have been thinking of the thymus (https://en.wikipedia.org/wiki/Thymus)?

Gravetto-Danubian
03-23-2016, 09:04 AM
It's a bit more complicated than that; if all bone marrow after childhood was replaced with adipose tissue, most adolescents, adults and elderly individuals would have clinical myelosuppression (how else will the RBC's, platelets and WBC's be made? :D ).

G-D is correct that, over time, the proportion of "active" (red) bone marrow slowly shifts towards the "inactive fatty" (yellow) form. By peak adulthood, just over half of an average person's marrow will remain red. In the elderly phases of life, the proportion of red dwindles to become a minority. Here's an instructive article on the frank characteristics of bone marrow over time (http://emedicine.medscape.com/article/1968326-overview#a2).

As you've mentioned a post-childhood milestone and near-complete replacement with fat, is there any chance you may have been thinking of the thymus (https://en.wikipedia.org/wiki/Thymus)?

Yes DMXX you're right
I perhaps inadvertently suggested that there was a sudden decrease in haematopoetic cells in marrow at the end of childhood rather than a gradual process

8324

(Thanks for making me revisit some very old notes )

zarkusa
03-23-2016, 09:40 AM
here is what 23andme (saliva test) says on topic :


If you have received a bone marrow transplant for the treatment of a condition or disease, we cannot recommend that you participate in 23andMe.

The saliva sample required for participation in 23andMe 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 would be unclear whether the results were based on DNA from you or from your donor.

I remember that once was a case reported on a community board of a 23am; customer had received results for his bm donor dna

search function doesn't work there , and I can't remember the details of how it was resolved :\

DMXX
03-23-2016, 11:09 AM
Yes DMXX you're right
I perhaps inadvertently suggested that there was a sudden decrease in haematopoetic cells in marrow at the end of childhood rather than a gradual process

8324

(Thanks for making me revisit some very old notes )

Wonderful. Always great to see some good histology slides as well.

Thank you for directly encouraging me to double-check the marrow transition stats; been a while since I learned that myself. :)

As a "fun" aside... I'm one of those super-rare people with a residual thymus (spoiler below folks...)


...I'm out of childhood, believe it or not! :D

Cornella
03-23-2016, 10:26 PM
Bone marrow (red) is the spongy tissue found within certain large bones in the body and is made up principally of haematopoietic stem cells. These are responsible for the production of red blood cells, white blood cells (wide variety of subtypes, general term leukocytes) and platelets.

The genetic information within a cell is located in the nucleus. Practically every cell in the body contains a nucleus, with the exception of red blood cells and platelets. The haematopoietic stem cells in bone marrow also have a nucleus.

Another important point to be considered here is all non-gonadal non-cancer cells within your body possess the exact same genetic blueprint in the nucleus. Everything from skin, white blood, nerve, muscle to gastrointestinal lining cells. As they deal with the body in its' entirety, we describe these as somatic cells (https://ghr.nlm.nih.gov/glossary=somaticcell).

A final point to consider is the material present in human saliva. Though overwhelmingly water (>99%), it also contains mucosally secreted antibodies (IgA), antimicrobial compounds (e.g. lactoferrin), enzymes (mainly salivary amylase), bacterial flora (hence the cause of plaques, cavities, gingivitis etc.) and... Human cells! These are chiefly either leukocytes (http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0765.1970.tb01835.x/abstract) or sloughed-off buccal epithelial cells (the lining of your inner mouth).

Returning to bone marrow replacement, there are two types of transplant;
1) Autologous; involves extracting fragments of healthy bone marrow from the patient and freezing them, destroying all their bone marrow (malignant and healthy tissue), then reinfusing the patient with their original healthy marrow (effectively a "self-owned reset")
2) Allogeneic; involves receiving healthy bone marrow from a different individual who matches the patient in terms of immunosignalling markers (referred to as the HLA type), destroying all their bone marrow (malignant and healthy tissue), then reinfusing the patient with their match's marrow

Tying the above together...
1) With an autologous transplant, neither blood nor saliva will be adversely compromised, as all the cell lines found in both are still fully derived from the patient/customer.
2) With an allogeneic transplant, things become trickier. Blood tests will produce the wrong result, as the leukocytes will be derived from the donor's stem cells. Saliva will be a mixed bag, as it'll contain both donor-derived leukocytes, or the patient's own buccal epithelial cells, which haven't changed (as epithelial cells don't derive from haematopoietic stem cells).

The solution with allogeneic transplant testees would be to either inform the testing laboratory of the situation when contributing saliva and see if they have techniques to isolate the epithelial cells and ignore the leukocytes (mechanical centrifugal separation might work, that is beyond my expertise), or, they can volunteer DNA from a non-haematopoietic derived somatic tissue (e.g. hair, skin).

Hope that's answered your question sufficiently!

[Edit]: Just seen this. Similar question asked to a trained biologist, near-identical answer as above (http://www.askabiologist.org.uk/answers/viewtopic.php?id=6352).


Thank you very much. My transplant was the tricky sort -- allogeneic. My donor was unrelated and anonymous, and of the same ethnicity and (I'm pretty sure) sex as me, so if I just take the saliva test blind, the data would superficially be similar to my own. Having my parents tested would be a handy way of ensuring I'm looking at my own results rather than the other person's, but I'm not sure which companies accommodate these kind of special situations. Interestingly, I may also inadvertently learn the identity of my donor if she's on 23andme.

Just another quick question: could the results I get back actually be a mix of my own and the other person's genome, or is it always an either/or situation? (I'm guessing the latter, and I know my DNA isn't a hybrid of me and the other person, but I'm wondering if they may use a combination of cells to reach my results, mixing myself and the other person).

DMXX
03-24-2016, 11:01 AM
Just another quick question: could the results I get back actually be a mix of my own and the other person's genome, or is it always an either/or situation? (I'm guessing the latter, and I know my DNA isn't a hybrid of me and the other person, but I'm wondering if they may use a combination of cells to reach my results, mixing myself and the other person).

Very good question. I don't know the answer to that. It depends on 23andMe's laboratory protocol. Perhaps someone with the necessary lab experience here knows what the consensus approach is in commercial testing. Alternatively, if you're still interested in finding the answer out, there's no harm in giving 23andMe's lab a quick ring to find out. :)

Also, I hope the transplant is serving you well and your health is better.