Mutations and Samples from Older People

[TSBinLV]

I have some questions for the cellular biologists out there. Pardon me if these are really stupid questions:

Isn't it true that as we get older, our cells do not replicate as accurately as when we are younger? Isn't this part of the cause of aging? If so, are there more chances for mutations when getting DNA samples from older people?

When FTDNA examines DNA samples, do they examine the DNA from a single cell, or do they insure accuracy by sampling several cells? Does anyone know?

I am wondering if samples from older people might not always reflect the actual DNA that was passed on to them by their parents.

Thanks....

[penguin]

Hi. I don't have an answer, but have wondered something similar. We have so many cells, each of which has mitochondrial DNA. When researchers talk about diseases caused by deletetions in mitochondrial DNA (often coding region, not the control region we have tested), they talk as if it is common to have mutations in some cells and not in others - which makes sense given how many cells we have. Sometimes, they look specifically at cells in the immune system or in muscle. Similarly, I read an article about some mitochondrial dna sequences that were especially prevelent in people who were 100 years old and twins- the suggestion was that this mito mutation was correlated with longevity (both twins and older adults face challenges). But they talked as if these mutations were just as likely to have occurred int persons lifetime than be inherited. Certainly seems to suggest we accumulate mutations.

Only mitochondria in sex cells will be passed on to the next generation. When we scrape our cheeks, we're getting skins cells. Somewhere, there must be some answer to the question of what the odds are that the skin cells will have the same mito dna as the sex cells.

I think when we scape the cheek cells, we must be getting a whole bunch and not just one. Still very small compared to all our cells though.

I'm new to this also, so if this is incorrect, I would appreciate if someone who actually knows points out and corrects the errors. thanks

[apriljb1]

Hi, this is a great question as I've been wondering this myself! When I mentioned to a friend I was having the mtDNA test done, he questioned the accuracy of such a test for these same reasons. We wondered if the various cells might vary in the mutations they carry throughout the body, including the mtDNA?.....So, it would just depend upon the "luck of draw" on which cells were being analyzed? I assume this isn't the case, but yes, would love a well informed answer! Thanks!

[Jim Denning]

ok ! me i asked my son junior college bio major he says all cells have the same core mutations can happen [miniscule] maybe from cancer with start/stop order cells but mutations wouldnt be much
example if i past my dads ydna to him 21 years ago and i had cancer of the mouth when i tested maybe something happens [small]
i am sure the experts will say no but sons have mutations from dads and between male cousins of the same grand father.yet other say mutations happen in 1000s of years.
i'de bet they dont happen much unless you live in chenoble love cannal or nagasaki
cells are cells that strand is always there because if it wasnt half would be you the other your brother or worse

when they say they happen in a 1000 yrs
it can be yr1
in another board they posted odds for relations something like 100% in 600yrs
it again can be year 1

[TSBinLV]

In order for a mutation to be passed from father to son, the mutation has to occur in the sex cell (sperm) of the father, and it has to be a mutation that leaves the cell healthy enough to fulfill its purpose. Many or most mutations will kill a cell or cause it to be cancerous. This is my understanding - I would love to hear from an expert here.

By the time most men have begun to age progressively they have already had all of their children. It therefore seems logical that mutations are not passed on very frequently because we usually have our children before we begin to age.

My understanding is that when we reach the point when we are aging fast, mutations are occuring much more frequently - and in fact this frequency has something to do with process of aging. So, if our cells mutate more frequently when we are aging, how is this affecting test results that are coming from older men?

If I am right about all of this, it seems we should all be aware of this and I would LOVE to hear from FTDNA regarding this matter.....

[T E Peterman]

I have wondered about this too. It seems that with each cell division, there should be roughly an equal chance of a mutation occurring. I don't see why this would accelerate with the production of germ cells.

The existing cells from a 90 year old man in 2005 would have had the same odds of mutation as the existing cells in his great-grandson in 2005.

So the age of all cell lines tested should date from 2005, rather than the birth years of the tested subjects.

I think is is plausible that a mutation could occur in the cell line giving rise to buccal cells, while the germ cells remain unchanged. This MIGHT explain apparent reversals from a father to son to grandson, where the middle generation has different results.

Timothy Peterman
Kansas City, MO

[TSBinLV]

The existing cells from a 90 year old man in 2005 would have had the same odds of mutation as the existing cells in his great-grandson in 2005.

Are you sure about this, because this is the main thing I am wondering about. I seem to remember reading that as we get older, our cell division is not as accurate and this is part of cause of aging. I could be wrong.

.....apparent reversals from a father to son to grandson, where the middle generation has different results.

There so there are cases where this happens? Wow.

[jaken24]

To List,

If I remember correctly, DYS mutations <repeats> are 'time based' mutations. Example: DYS 385a/b are fast movers, perhaps every 7 generations; keyword generations.
Example: the average generational difference in my family is 34 years. <long>
Someone else may have an average of 20 years. <short>
Given the above information, a direct line male can expect to find a change in DYS 385a/b every 248 years <7 generations> where as the other example can expect a change every 140 years <7 generations>.
The rate of change can be even greater in a slow mover, say one that changes in 20 generations: in my family that would be 680 years, in the other example that would be 400 years.
This is not an exact science.

Jeff

[T E Peterman]

No, I am not sure about this. I am NOT a cellular biologist. I just know a bit about cellular biology. I have wondered if the "common sense" logic is really right.

Are the odds really the same of a mutation in any cellular division?

If there are different odds of mutations in different cellular divisions, why is this? Perhaps the "correcting enzymes" within a cell don't function as well if a germ cell is being created.

Why do older people have more mutations in their cells? Is it simply because they've been around longer & have accumulated more mutations? Or is it because biological systems are failing?

The mutation rate in the y-DNA loci that are tested is so low that most of this is neither her nor there. If one of the 25 markers had a different count in an older person, odds are it wouldn't be out of variance for a typical generational mutation.

The best strategy is to test two descendants from the most distantly confirmed ancestor. If they match or come close, we can say that we have a high quality representation of what the y-DNA (or mtDNA) of the most recent common ancestor was.

Timothy Peterman
Kansas City, MO

[EBurgess]

I am no expert here, but when you are providing a sample with millions of cells. The overwhelming number of genes will be the same regardless of how many X-rays you have had or how old you are. The bulk of the genetic material will overshadow any of the damaged cells that were in the sample.

Any mutations seen in the results would have to mean that the mutation came from the germ cells that produced you, in other words from the y-chromosome from your father for a Y-DNA test.

Eric.

[TSBinLV]

Part of my original question was: How many cells are included in the testing? (or something to that effect) If indeed many cells are included in the testing, then yes I agree with you that the majority of the cells would contain the original information from the germ cells.

I know nothing about the testing process. Is it safe to assume that many cells are used in testing? Is that how this kind of testing is normally performed? Or is just a single cell used? Does anyone know anything about the testing process at FTDNA?

[T E Peterman]

Good point E. Burgess.

In order for all cells to have a bogus mutation, the mutation would have had to have occurred in the stem cells before differentiation. This is close enough to the point of conception that we can say for all intents & purposes, it was at the point of conception.

Timothy Peterman

[AngelaC]

Agreed

Good point E. Burgess.

In order for all cells to have a bogus mutation, the mutation would have had to have occurred in the stem cells before differentiation. This is close enough to the point of conception that we can say for all intents & purposes, it was at the point of conception.

Timothy Peterman

I pretty much agree with this,...the only thing I'll add is that as a person ages, a person might have some somatic mutation in their cheek cells, - but the majority of cheek cells will contain the original sequence - outnumbering any mutants, so for all intents & purposes the DNA results will reflect the DNA they had at conception.

Angela.