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  • Whe Do Mutations Occur

    When do mutations occur? At conception? During embryonic development? During normal lifespan? Could two brothers have a haplotype mismatch, due to one (firstborn) inheriting a non-mutant Y-chromosome and the second brother inheriting a mutated Y-chromosome!] When a new mutation occurs in generation "x", do all of the generation x person's chromosomes exhibit the change or just the one in the spermcell that is passed-down?

  • #2
    Answers to your questions

    "When do mutations occur? At conception? During embryonic development? During normal lifespan?"

    Mutations occur all the time, and almost all the time they are fixed by the body's normal repair mechanism. They can happen at conception (although that is a brief instant in time and not likely). They can happen during embryonic development, although only mutations that occurred to the Y chromosome in the sperm cells of the embryo would be passed on to the next generation. They can happen during normal lifespan, again with the understanding that while they happen to all cells, it only matters if they happen to the sperm cells and can be passed on.

    "Could two brothers have a haplotype mismatch, due to one (firstborn) inheriting a non-mutant Y-chromosome and the second brother inheriting a mutated Y-chromosome!]"

    The father only has ONE Y chromosome in all of his cells. There is no mutant Y and normal Y. It could be that one of the Y chromosomes in the father's sperm cell became mutated. The more likely answer is that the two brothers have different fathers.

    "When a new mutation occurs in generation "x", do all of the generation x person's chromosomes exhibit the change or just the one in the spermcell that is passed-down?"

    Only the cell that had the mutation and the cells that were produced from that cell. And it has to be a sperm cell where the Y mutation took place or it couldn't be inherited.

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    • #3
      when and where mutations happen

      Hmmmmm.....

      Isn't meiosis (process by which sperm are produced) the most likely place for a mutation to occur? Even if this is an extremely rare event. There are 100 million to 400 million sperm in one single ejaculate.

      I mean that is the only time when the genetic material for the Y-chomosome is tampered with just prior to recombining with an X to produce a new person.

      I submit that noone really knows for sure what causes mutations, there are many likely culprits. Brothers will most often have identical Y-chromosomes. I do believe however it is possible to have a single mutation difference between brothers, after all its gotta happen somewhere.

      If two brothers test say 37 markers and one has a single extra repeat somewhere I think it is more likely than not that they are in fact genetic brothers.

      E.

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      • #4
        Originally posted by EBurgess
        Hmmmmm.....

        Isn't meiosis (process by which sperm are produced) the most likely place for a mutation to occur? Even if this is an extremely rare event. There are 100 million to 400 million sperm in one single ejaculate.

        I mean that is the only time when the genetic material for the Y-chomosome is tampered with just prior to recombining with an X to produce a new person.

        I submit that noone really knows for sure what causes mutations, there are many likely culprits. Brothers will most often have identical Y-chromosomes. I do believe however it is possible to have a single mutation difference between brothers, after all its gotta happen somewhere.

        If two brothers test say 37 markers and one has a single extra repeat somewhere I think it is more likely than not that they are in fact genetic brothers.

        E.
        Kind of hard to say where most mutations take place. There are several reasons for mutations. One is unequal pairing of one copy of a chromosome with another, but that doesn't happen with the Y chromosome because the male only has one copy. Unequal crossing over in mitosis (the division of cells to make other cells that are NOT sex cells at about the same frequency as it does in mitosis, but it doesn't much matter as the cell just dies off (unless it's a sex cell).

        Then there are transposons and retroviruses inserting themselves into the DNA and causing mutations. Then there are external stimuli, like radiation. We used both radiation and transposons in the lab to CAUSE mutations to disrupt genes on purpose to see what the results of the mutation was and what the original gene was supposed to do that wasn't being done anymore.

        But the point is that mutation is pretty much random and not able to be predicted (with the exception of purposely inserting a transposon into a plasmid, shocking the cell forcing then plasmid in, shocking it again so the plasmid will jump out and insert itself into the organisms DNA).

        Unequal crossing over in an area with tandem repeats can proceed with no damage to the host. Same with transposons, particularly if it inserts into the many tandem repeat (aka junk) areas of DNA (estimated to make up about 95% of the DNA in our bodies)!

        Comment


        • #5
          Thank you for the reply Lizzie.

          The last part of Wolong's question is easy to answer all somatic cells will have the mutation that arose from that persons germ cells.

          The other question, whether or not two brothers can have a difference in their y-chromosome you respond:

          "The father only has ONE Y chromosome in all of his cells. There is no mutant Y and normal Y. It could be that one of the Y chromosomes in the father's sperm cell became mutated. The more likely answer is that the two brothers have different fathers. "

          Help me with this because I am not quite sure what you are saying? We both agree a mutation in the non-sperm cells of my body cannot be transmitted to my offspring. In other words the y-chromosome in my somatic cells are all identical.

          I accept your critique that meiosis may not be the main source of mutations, you explianed that well but...

          Just to be clear...

          A heritable change would have had to occur in the precursor cells to my sperm or in a sperm cell itself... Therefore in my mind this is the place for the change to take place and by extension to this logic. Some Sperm cells may be different from others generated by one man. So brothers can have a slight mismatch in one locus.

          Why do you end by saying: "The more likely answer is that the two brothers have different fathers "

          Most of the time this is true, as it is with father to son, but not always.

          Comment


          • #6
            I hope this answers, but it is really just my opinion

            There are three different scenarios that could result in an altered DNA sequence in a sperm cell (remembering of course that the sperm cell has 23 chromosomes, and we're looking for a mutation in the Y chromosome).

            It could have happened in the original precursor sperm cell and then all the cells arising from that one would have the mutation. The brothers would have the same DNA.

            It could have happened in one of the clones of the precursor, and then the percentages of altered Y chromosomes would decrease depending on how many mitoses since the precursor it happened. If at the second division, then there would be 3/4ths of the final sperm that were one way, and 1/4th that were a different way. The more times it divides, the fewer mutated Y chromosomes there are.

            It could happen during meiosis, either in meiosis I or II. If it happened in meiosis I you'd have four, in meiosis II you'd have two mutated Y chromosomes. Once it reaches meiosis, there are no more divisions.

            Now, I would imagine that since mutations don't much matter in the Y chromosome in the cell except in extremely rare instances, that the cell would go on and become a sperm cell capable of impregnating an egg. But there are several million sperm cells released at the same time, and one of those few sperm cells would have to beat out the others to succeed.

            So, the only scenario that there is really any likelihood of two brothers with the same father having different Y DNA would be if the mutation took place in one of the very early divisions, and that's even pretty much of a long shot. Depending on how many divisions there have been since the precursor cell the formula would be that you would raise 2 to that power. If there had been ten divisions, for instance, you'd raise 2 to the 10th power and the chances that the two brothers would have different Y chromosomes would be 1/1050.

            One other thing. Since the chance of one mutation is 1/1,000,000, even in the rare case of two different Y chromosomes with a single mutation, the mutations wouldn't be that big, and the two individuals would have Y chromosomes that were only slightly different. For more than one mutation to take place, the odds are that you would multiply 1,000,000 x 1,000,000 for each mutation.

            Much more likely that they had two different fathers, don't you think?

            Comment


            • #7
              I just realized that I made a mistake. In the case of a mutation during meiosis I, you'd end up with either a child with Kleinfelter's syndrome (XXY), an abnormal male with some female features, or one with an X from his mother and a X with a piece of Y attached, or you'd end up with no Y at all which results in Turner's syndrome (XO), which is a girl, although one who is abnormal. If it took place in the second meiosis, you'd have either Turner's syndrome or you'd have a supermale (XYY). In any case, it would be obvious when looking at the chromosomes that this had happened.

              Comment


              • #8
                opinions are always welcome!

                I learn something with every post, so please feel free to express your opinions, I promise no bashing

                Let me start by saying that I have not been in a university level bio course in 15 years. Therefore I approach the subject as a layperson and try and apply common sense.

                The reason I persist in this thread is because the answer (if there is one) is important to me.

                Two brothers come to test and say one comes back with a 464e marker and the other does not have it. What do we tell him? I am sorry to inform you...one of you is illegitimate!

                My stance is that they ARE related, I believe your stance is that they are NOT? I don't see why we can accept a one step mutation in a father to son transmission but we can't accept one to another male sibling?

                Getting back to the where a mutation can happen it occurred to me that this can happen post conception when there is just a blastoceal with undifferentitated cells. If a mutation were to occur at this stage in cells that were destined to be part of the reproductive machinery. This mutation could then be replicated and passed on.

                E.

                Comment


                • #9
                  Lizzie and EBurgess,
                  This forum is all about being able to identify people because of mutations that happen over time (and very rarely/infrequently). Please take a look at the phylogenetic tree for the Y-chromosome at www.familytreedna.com/haplotree.html From what I have read, a single mutation, between father and son, is possible without other full biological brothers (younger and/or older) having this same mutation. If this were not true there are a lot of people that have spent alot of money for nothing.
                  Don Potter

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                  • #10
                    Thanks for your post Don,

                    Check out this article.

                    http://www.wired.com/news/technology..._story_related


                    Here is one quote:

                    "The rate of mutation is greater in sperm production than in egg production," said John McPherson, co-director of Washington University's Genome Sequencing Center. "It may be that the increased production rate in males results in more chances for mutations to occur."

                    On a side note I am getting addicted to this Forum! The quality of the posts keeps me coming back.

                    E.

                    Comment


                    • #11
                      Originally posted by wolong
                      When do mutations occur? At conception? During embryonic development? During normal lifespan? Could two brothers have a haplotype mismatch, due to one (firstborn) inheriting a non-mutant Y-chromosome and the second brother inheriting a mutated Y-chromosome!] When a new mutation occurs in generation "x", do all of the generation x person's chromosomes exhibit the change or just the one in the spermcell that is passed-down?
                      When do mutations occur?
                      I have no idea when mutations occur and for all practical purposes in genealogy, I don't really think it makes a bit of difference. Remember, in Y-chromosome testing we are talking about a mutation in one of the many markers on the Y-chromosome. All total there are over 40 such markers that are tested by the several companies doing testing. We are not dealing with a large scale mutation, just a simple small mutation in one or possibly more markers.

                      Could two brothers have a haplotype mismatch?
                      Yes it is very possible for two brothers to mismatch on a single marker. If you test 25 markers and assume a mutation rate of 0.02, there is a 60% probability that father and son will match on all 25 markers. There is a 30% probability that father and son will mismatch on 1 of the 25 markers.

                      When a new mutation occurs in generation "x", do all of the generation x person's chromosomes exhibit the change or just the one in the spermcell that is passed-down?
                      I'm not quite sure what you are asking here. In the case of Y-Chromosome testing the only thing we are interested in is the Y-Chromosome. Each male has one Y-Chromosome which he passes on to his male children. If there is a mutation in the Y-Chromosome that he passes on to a son, the son will carry the "mutated" Y-chromosome and pass it on to his male children. All his children will carry the "mutated" Y-chromosome unless another mutation occurs.

                      John

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                      • #12
                        Can have differences between brothers

                        Hi All,

                        My understanding is (as Don says) that you can have differences between brothers.
                        I think, Lizzie, that the processes & modes of mutation that you know from your experience in microbial genetics don't apply with these Y-chromosome junk DNA single tandem repeats. It's transcription "slippage" that is thought to cause these mutations, most likely during meiosis. So the transcription mistake (which can cause either an increase or decrease in the number of repeats), may occur in one sperm cell, but not neccessarily in any of the others.

                        In any case, if the mutation occurred after the formation of the zygote, & occurred early enough so that the mutation occurs in most of the resulting persons cells, - that resulting persons brothers wouldn't have the same mutation, thus it is possible (regardless of when the mutation occurred) for one brother to have a mutation, and another brother not.

                        Angela.
                        Last edited by AngelaC; 6th February 2005, 12:31 PM.

                        Comment


                        • #13
                          You're right!!!

                          I hadn't even considered post conception mutations. If the son had a mutation at the first mitosis or even at the second and the first cell didn't divide again, you could definitely have two sons with a different Y chromosome. Because the testing takes place at sites of tandem repeats, an unequal crossing over could even result in a fairly significant change at that particular site still resulting in a viable cell.

                          You can definitely see more mutations in the Y chromosome because the vast majority of it doesn't code for any gene. If there's a mutation in the Y chromosome, there are no ill effects to the person or to his sons because there is not a case of a necessary protein NOT being produced. When there's no ill effect, the mutation is harmless, and the cells arising from that mutation, as well as the germ cells, are still viable.

                          On the other hand, if the mutation happened on another chromosome and hit an area that coded for a protein product, the cell would either die, or a sperm cell arising from that cell would most likely be very detrimental to the offspring if the cell could limp along with a mutated gene.

                          It's not that the Y chromosome is more likely to have mutations. It's just that the mutated chromosome would survive where mutations in other chromosomes most likely would not (we hope!).

                          Comment


                          • #14
                            Originally posted by jablair
                            [B
                            Could two brothers have a haplotype mismatch?[/B]
                            Yes it is very possible for two brothers to mismatch on a single marker. If you test 25 markers and assume a mutation rate of 0.02, there is a 60% probability that father and son will match on all 25 markers. There is a 30% probability that father and son will mismatch on 1 of the 25 markers.
                            John
                            Um? being a layman on this subject, if 2 brothers shared the same Y gene, but 1 brother had 1 dns mutation, how does that put that 1 brother into a different haplo? For this, I will assume the father is in fact the father.

                            The idea of being placed in a different haplo just because of 1 marker mutation between father and son just doesn't make any since to me at all.
                            So If I were to follow that concept, assuming "a" mutation were to occur several times over the generations with in the same family, it would occur to me that it would be possible for one family line to be placed in each of the halpo's just because of 1 marker mutation, depending on which marker was the mutation? Meaning 1 generation could be one haplo and another generation could be placed in yet another haplo? See what I am getting at? Hard for me to explain lol, I am new to this but I sort of have a small grasp on it.
                            The short and simple of what I am getting at is, if the father and son were confirmed to be in one haplo, the mutated son to me should continue to be in the same haplo, but note the mutation. To put the mutated son into a different haplo is the part I am having trouble understanding. He isn't really a different haplo, all he is a 1 marker mutation difference to his father. Thus, they all are with in the same haplo but one known mutation occured Right?

                            Confused lol.

                            Comment


                            • #15
                              Originally posted by Donald Locke
                              The short and simple of what I am getting at is, if the father and son were confirmed to be in one haplo, the mutated son to me should continue to be in the same haplo, but note the mutation. To put the mutated son into a different haplo is the part I am having trouble understanding. He isn't really a different haplo, all he is a 1 marker mutation difference to his father. Thus, they all are with in the same haplo but one known mutation occured Right?
                              Donald,
                              I think you are confusing the terms haplotype and haplogroup.

                              Haplogroups (which you are referring to) are tied to deep ancestry (think 10,000 or 10's of 1000's of years) and are represented by groups such as R1b, E3b, I, Q, N, etc. A SNP test of the Y Chromosome, which tests deep ancestral Markers, determines the Haplogroup.

                              Haplotypes (which I am referring to) are simply the results of your Y-chromosome STR test, ie your 12, 25, or 37 marker test results. People who are an exact match on the 12 marker test have the same 12 marker Haplotype, people who are an exact match on the 25 marker test have the same 25 marker Haplotype and people who are an exact match on the 37 marker test have the same 37 marker Haplotype. One or more msimatches on any markers means you have a different Haplotype.

                              One way to think about Haplogroups is that a Haplogroup is a branch on the tree of Homo Sapiens Sapiens and a Haplotype represents the leaves of the tree. All the Haplotypes that belong to a Haplogroup are leaves on the same branch.

                              A father and son can have different haplotypes but they cannot be different haplogroups.

                              For more on haplotypes and haplogroups see http://www.familytreedna.com/hap_explain.html

                              John

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