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apophis99942
03-04-2013, 10:58 PM
Pardon my ignorance, but is it possible to have two mtDNAs (maternal and paternal) present in the same person naturally before any surgery has taken place?

If this is true, does it then make sense to test the muscle mtDNA separately?

If so, then which population groups tend to have the highest likelihoods of paired mtDNAs in the same person pre-op?


Sequencing of blood mtDNA from the patient's healthy parents and from his paternal uncle demonstrated that the haplotype of the patient's muscle mtDNA was identical to that of his father's and uncle's blood (with the exception of the 2-bp deletion, which was found only in the patient). The haplotype of the patient's blood was identical to that of his mother. Analysis of mtDNA from both blood and muscle of the patient's sister found only the maternal mtDNA haplotype (data not shown).


The mtDNA from the patient's blood, hair roots, and cultured fibroblasts showed only the maternal haplotype.

The source (http://www.nejm.org/doi/pdf/10.1056/NEJMoa020350) for the above statements.

thetick
03-06-2013, 12:44 AM
The paper is from the NEJM which is highly respected. Since the papper is from 2002 it certainly was peer reviewed and any if false information was fond the paper would have been removed. Anyway that's the way it should work.

I suspect it's legit but very rare. Just like one can have XXY (Klinefelter syndrome).

apophis99942
03-06-2013, 05:32 AM
Does Klinefelter Syndrome require the presence of both paternal and maternal mitochondrial lineages in the patient? Or has this simply never or not usually been tested for?

Ann Turner
03-06-2013, 07:21 PM
Pardon my ignorance, but is it possible to have two mtDNAs (maternal and paternal) present in the same person naturally before any surgery has taken place?

If this is true, does it then make sense to test the muscle mtDNA separately?

If so, then which population groups tend to have the highest likelihoods of paired mtDNAs in the same person pre-op?





The source (http://www.nejm.org/doi/pdf/10.1056/NEJMoa020350) for the above statements.
That was a single case report, which involved a pathological change in the paternal mtDNA. Ordinarily, very few paternal mtDNA molecules enter the fertilized egg, and those are recognized and eliminated by some mechanism in the egg. It's possible that the pathological change interfered with the recognition process. After that report came out, many cases of mtDNA disorders were examined without finding another instance.

Klinefelter's is a result of faulty partitioning of the maternal and paternal chromosomes. When things work right, the paired chromosomes in the father split so that each sperm has exactly one copy of each chromosome, and ditto for the egg. But occasionally, the egg/sperm receive both chromosomes (or none). This is called "aneuploidy" (an abnormal number of chromosomes). Trisomy 21 (Down's syndrome) is another example of aneuploidy.

apophis99942
03-08-2013, 01:28 AM
Yes, but:

- how does one account for heteroplasmy? Or is it simply sample mix-up/contamination of forensic cases?

- why should one necessarily label the NEJM case as "pathological"? What if the patient had inherited some good bio trait from his paternal mtDNA?

Source (http://en.wikipedia.org/wiki/Paternal_mtDNA_transmission)

Ann Turner
03-09-2013, 05:43 PM
Yes, but:

- how does one account for heteroplasmy? Or is it simply sample mix-up/contamination of forensic cases?

- why should one necessarily label the NEJM case as "pathological"? What if the patient had inherited some good bio trait from his paternal mtDNA?

Source (http://en.wikipedia.org/wiki/Paternal_mtDNA_transmission)
Heteroplasmy occurs when one mtDNA molecule (out of thousands in a cell) has a mutation. This is happening all the time, but most of the time it's not detectable. I wrote a column about it for JoGG.

http://www.jogg.info/21/SatiableCuriosity.pdf

The patient was studied because of lifelong severe exercise intolerance due to mitochondrial dysfunction.

http://www.nejm.org/doi/pdf/10.1056/NEJMoa020350

apophis99942
03-09-2013, 06:32 PM
So one's mtDNA haplogroup assignment at a DNA test = >20% of the total mitochondria?

Ann Turner
03-09-2013, 07:30 PM
So one's mtDNA haplogroup assignment at a DNA test = >20% of the total mitochondria?
I'm not sure I understand. The haplogroup assignment is based on results for many different positions on the mtDNA molecule. Heteroplasmy at one position wouldn't change the whole haplogroup assignment.

apophis99942
03-11-2013, 09:24 AM
I meant 20% of the entire mtDNA molecule having positions which are heuristically common to one haplogroup rather than another.

So you're also saying that heteroplasmy seldom if ever occurs in more than one place simultaneously?

I think that there is a great lot about this that I misunderstand as well.

jlick
04-19-2013, 04:33 AM
I meant 20% of the entire mtDNA molecule having positions which are heuristically common to one haplogroup rather than another.

In my experience, heteroplasmy often occurs at random locations which are not defining mutations for the particular haplogroup for which the person belongs. The exception is for mutations which are known to be unstable, which is probably a reversion in progress. In any case, heteroplasmy seldom has an effect on the haplogroup assignment. I have added special handling to mthap for heteroplasmy matching, but actually I was unable to find a case where it made any difference.


So you're also saying that heteroplasmy seldom if ever occurs in more than one place simultaneously?

Multiple detectable heteroplasmy is extremely rare.