simmo wrote:So Cranius - if you have the time and inclination give us a summary of the current issues facing this case! You're much more knowledgeable than me.
Feel free not to bother if you don't want to.
As it stands, the only thing we really know is that second batch of DNA has returned from the FSS in Birmingham. These tests are believed to more specific and hence took longer to analyse. This may form the basis some new questioning by the PJ.
I'm as perplexed as the next person with all the claims and counter-claims. I was just looking a the Mirror Forums, which is a hotbed of speculation and outrageous assertions--a kind of cyber-lynchmob--and someone purporting to have some understanding of DNA has outlined the relevance/irrelevance of Madeleine's paternity. They are saying that it's not necessarily crucial in distinguishing Madeleine's DNA from her sibling's.
Someone on the Mirror Forums wrote:There seem to be a great many questions on the forum today dealing with DNA. I thought I would attempt to shed a bit of light on some of the issues involved with DNA testing when someone goes missing. CAVEAT: I was a biochemistry major at college, but that was a distressingly long time ago. LOL I have some experience with forensics, and we have a geneticist in the family who supplied most of the information I shall be providing; however, times have changed and the field is so complicated in comparison to what I was taught years ago that I may not have got the information down right. I believe there are at least a couple of people here who are doctors or biologists, so feel free to jump in and correct me if I am wrong.
I should also like to say at the outset that I do not believe we should be speculating about whether or not Gerry McCann is Madeleine's biological father. As you will see from information below, there are plenty of genetic differences between siblings that should make it possible to differentiate the DNA of one from another whether or not they have the same father. I have my suspicions about the part the McCanns may have played in Madeleine's disappearance, and certainly the very private information that Madeleine was conceived via IVF came into the public arena from them. Nevertheless, I think it unseemly to speculate about the most personal aspects of these people's lives. Just my opinion on that point . . .
When a person disappears and it appears likely that it may be necessary at some point to try to make an identification, one of the first things that law enforcement attempts to do is to get a profile of the person's nuclear DNA. The nuclear DNA of an individual is absolutely unique, except in the case of identical twins who come from the same egg. (There is even a test based on a concept called methylation that can distinguish the DNA of identical twins based on spontaneous mutations that occur after birth , but it has not been developed enough to be used in court and no one involved here is an identical twin anyway.)
There are two types of DNA: nuclear and mitochondrial. Nuclear DNA is contained in the nucleus of every cell in one's body, and it is what determines one's genetic heritage (color of eyes, hair, inherited tendencies to disease, height, etc., etc., etc., etc., etc.). Mitochondrial DNA (mtDNA) is contained in the mitochondria, threadlike structures that occur in all cells except mature red blood cells and play a part in metabolism. While an individual's nuclear DNA is unique, one inherits one's mitochondrial DNA from one's mother, and the mtDNA of a child such as Madeleine will be identical to that of her mother, grandmother, aunts, sisters, etc. Therefore, for forensic purposes, it is very important to try to obtain a sample of nuclear DNA.
Nuclear DNA can be extracted from many sources even after a person goes missing. Examples include but are not limited to toothbrushes, sippy cups only used by one child, pacifiers, used chewing gum (gross but true), blood samples that might be left over from previous lab tests, parings from fingernails or toenails, skin cells that might have rubbed off on clothing such as a hatband, or hairs that still contain the follicle (root). Hairs that do NOT have the root attached can still be useful in determining mtDNA, but in order to extract nuclear DNA, the follicle must be attached. This is referred to as the "known sample."
When one goes missing, the family is often asked to provide these articles so that a DNA profile can be at the ready. (Remember newspaper reports of family members of the missing being asked to provide hair brushes and toothbrushes after the Twin Towers collapsed in New York? Many people were identified that way.) I have not seen press reports saying that this was done in Madeleine's case; however, it would be standard procedure.
Most DNA analysis these days is accomplished using short tandem repeats (STRs). STRs are short sequences of DNA that lie head-to-tail within the nucleus of a cell and consist of pairs (called "base pairs") of the four organic compounds that are the building blocks of DNA. There are at least 10,000 STRs within the human genome, and each one of them contains a number of variations (from hundreds to thousands) in how the base pairs are arranged. While one inherits ones genes from one's parents, the arrangement of these variations is unique to the individual.
In determining the DNA "fingerprint" of an individual, the STRs that cluster at a particular area with an identifiable location called a "marker" are mapped by feeding data into a computer program. This yields a printout containing "peaks" and "valleys" that look something like the paper printout one gets from an electro-cardiogram (EKG).
When a sample of DNA is found during an investigation that may or may not belong to the missing individual (a "questioned sample"), it is subjected to the same process as the known sample, and the two printouts are compared.
A few additional comments:
(1) Different jurisdictions test differing number of DNA markers, depending on what laws and court decisions have determined to be legally sufficient to say whether or not the questioned sample matches the known sample of the person's DNA. 10, 15, 20, or 25 markers are commonly tested. In the UK, the standard is 10. Portugal tests either 20 or 25. (I have seen both numbers in press reports.) I presume that the PJ has requested that the FSS use whatever number of markers are normally tested for in Portugal, in order to ensure that any DNA evidence will stand up in court.
(2) Due to degradation caused by factors such as time, heat, fire, attempts to "clean up" an area containing DNA with cleaning products, or other factors, it is sometimes not possible to obtain the full number of markers that one normally uses from a questioned sample. In those cases, the number of markers that cannot be teased out of the questioned sample of DNA are said for statistical purposes NOT to be a match to the known sample; this yields a result in favor of the defendant, which is as is should be. For example, if a 20-marker test is used and STRs can be extracted from only 15 of those locations, but the DNA that is extracted is a match, then the questioned sample is said to be a 75% match to the known sample. Based on press reports, this is what I believe has happened to at least some of the DNA samples in Madeleine's case: all the markers that could be extracted were matches, but the number of markers normally used could not be extracted from the sample due to degradation of the DNA. While not a "smoking gun" in terms of evidence, this would still have considerable probative value.
(3) DNA matches are not expressed as "100%." If all markers match, however, the probability of the questioned sample coming from the same person from which the known sample was obtained is far greater than 99%.
(4) Approximately 99.9% of all human DNA matches. Yes, you read that correctly. The DNA of the most profoundly retarded person who has ever lived on the planet was 99.9% identical to Albert Einstein's. The DNA of the poorest beggar on the streets of the poorest country in the world is 99.9% identical to that of the Queen of England. (This should give us pause in thinking we are superior to others, methinks.)
However, within that .1%, an enormous number of variations can occur. (Remember that there are believed to be approximately 10,000 STRs in the human genome, and each of them contains varying numbers of base pairs of building blocks of DNA ranging from the hundreds to the thousands.)
Here's the thing as it relates to this case: The DNA of brothers and sisters varies by about .05%. In other words, your DNA is about twice as similar to your siblings' as to an unrelated person you meet on the street, BUT GIVEN THE ENORMOUS POSSIBILITY IN THE NUMBER OF VARIATIONS, IT IS STILL PERFECTLY POSSIBLE TO DISTINGUISH BETWEEN THE DNA OF SIBLINGS. That is why it doesn't make a great deal of difference whether or not Madeleine and the twins have the same biological father. Madeleine's DNA is still unique to her, and testing could easily differentiate her DNA from that of her brother and sister.
(5) One press report said that Madeleine's DNA profile had been determined by "cross-matching" the DNA of her parents. Can't be done. That was an attempt to over-simplify that leaves one with the wrong impression. If no known sample of Madeleine's DNA could be obtained, it would be useful to obtain blood samples or buccal swabs from the inside of their mouths in order to have information about her parents' DNA at the ready, but this could be used primarily for the purpose of excluding a questioned sample as belonging to Madeleine. (Since all Madeleine's genetic inheritance comes from her parents, the finding of any DNA that did not match her parents' would tend to indicate it did not come from her.)
Alternatively, if known samples of DNA were obtained from Sean, Amelie, Gerry, and Kate McCann and genetic "fingerprints" developed for all of them, and a questioned sample had the same genes, just arranged in a different pattern, there is a very high probability that it would be Madeleine's. But that's all you could say about it. Without that printout from the known sample showing the "peaks" and "valleys" of Madeleine's DNA profile, you could not say with 99.9999999% certainty that any DNA found was hers.
(6) If today’s press reports were correct and Gerry McCann is not Madeleine’s biological father, Madeleine, Sean, and Amelie would still have DNA that was 99.95% similar if their bio father is the same. If he is not, their DNA would be more than .05% but less than .1% different, as a result of having the same mother.
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I would hope and expect that the PJ continued trying to extract Madeleine's DNA from various possible sources, such as her toothbrush, hairbrush, the little hat she was wearing in some of the pictures, her pillow at home in England (provided her brother and sister didn't also sleep on it), etc.
Sequencing her parents' DNA from samples of their blood in the meantime would be helpful, as it might make it possible to exclude some DNA samples that might have been found, but to establish beyond a reasonable doubt that questioned DNA came from Madeleine, you'd need her DNA profile.
I do not know what court rulings in Portugal say about reasonable doubt, but when you are asking for 20 years of a person's life (as one could be in a murder case) the standard must be very, very high.
If a known sample of Madeleine's DNA was not obtained, then this is the best you could do: The prosecution presents to the judges the results of DNA analysis of Gerry and Kate McCann and analysis of the questioned sample of DNA that is believed to have come from Madeleine. The three samples will not be an exact match. All the prosecution can truthfully say is something like this: Analysis of these DNA samples reveals that the questioned DNA found [wherever] does not contain any genetic material that would exclude it as coming from an offspring of these two people. Since the DNA samples are very similar, we believe that there is a high probability that the questioned sample came from Madeleine McCann.
There was an interesting case in America a couple of years ago where a young girl named Natalee Holloway went missing while on vacation in Aruba. (She has never been found.) Press reports said that DNA samples were obtained from both her parents in an effort to determine whether some hairs that were found on duct tape on a beach were hers. Based on a comparison to her parents' DNA, they were able to exclude the hairs as belonging to Natalee.
The authorities continued trying to get a sample of Natalee's known DNA, however. When they analyzed the toothbrush she had with her, they found male DNA. So far as I know, no one ever determined who it belonged to. The relevance of the story of Miss Holloway to the McCann case is that even when authorities have DNA samples from the blood of both parents, they still continue analyzing personal items in order to try to find a sample of known DNA from the missing person.
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My view is that the main complication presented by low copy number (LCN) DNA analysis is that it takes a lot longer than other methods of analysing DNA. I expect that this is why it has taken so long to get some of the DNA results in this case.
"Forensic Science International," probably the premier scientific journal in the area of forensics, has this to say about LCN: "Routine analysis of STR markers is highly discriminating and can be used for small amounts of DNA using the LCN strategy."
I know the professor from Wayne State University in America probably would not agree on this. In every area of science, there are contrarians who do not agree with the conventional wisdom, and these often are the people hired to testify as expert witnesses for a particular position. (I do not mean "contrarian" here in a negative way, as people who swim against the tide are sometimes those responsible for keeping science honest.)
I will say this, however: I believe that the FSS is, without question, the best DNA lab in the world. If I were an innocent person who was a suspect in a crime and they were performing DNA analysis on the case, I should be content to have my fate in their hands. If I were guilty and heard that they were on the case, I would be heading for the Himalayas - by yak, so as to leave no trail of reservations behind me.
I should not be at all surprised if, when the DNA analysis is finally received, neither side is completely satisfied. In a situation like this, that is another indication that you've a good piece of science on your hands, in my opinion.
--------------------------------tas2 wrote:I posted this on another thread but perhaps this is a better place for it...
It's late and I'm tired and not as perky as I should be but..... here's my question: surely it's easy to determine whether or not Gerry is Maddy's dad. And how can they say they've cleared the 'bio dad' unless they are 100% sure? This is not a case of maybe, he either IS or he ISN'T. Right? Someone suggested Kate conceived naturally while undergoing IVF but then the PJ wouldn't have been able to rule out the bio dad... unless he wasn't a ***** donor, but in that case he wouldn't be 'cleared' either.
This matter of paternity is so easy to determine that it would seem very foolish to tamper with this subject to gain support. For either party. So I'd go along with the 'leak' except for the checking of the bio father.
Can you clarify?
Thanks if you can!
I'd really rather not get into this, as I do not feel, as I stated in my OP, that this is something we should be speculating about. You've asked an honest question, however, so I will attempt to provide an honest answer, but this is all I'm going to say about the matter of Madeleine's paternity.
If a known sample of Madeleine's DNA is in hand, it makes no difference who her parents are. Any questioned samples of her DNA found in the boot of the hire car or the apartment or wherever can be compared to the known sample with an extremely high degree of accuracy, assuming that both the known and questioned DNA samples were in good enough shape that they were able to obtain a satisfactory number of markers from them.
If a known sample of Madeleine's DNA is not available, then one must know who her biological parents are and have a DNA sample from both of them before any comparison of her DNA to theirs would be useful. Merely the fact that Madeleine was conceived by IVF would not mean that Gerry McCann could not be Madeleine's biological father. The only child of our best friends was conceived by IVF using her mother's egg and her father's s**** (still cannot believe you can't use that word here); the egg was fertilized in a petri dish and then implanted in her mother. This was necessary because her mum's fallopian tubes were blocked, a "mechanical" problem easily overcome by IVF if both parents are producing what is needed to make a baby.
If Gerry McCann is not Madeleine's bio father, then obviously an analysis of his DNA will tell you nothing about hers; there'd be no point in even obtaining a sample from him except to rule him in or out as a possible source of other DNA that might have been found in the apartment or car. The bio father would have to be found and a sample of his DNA obtained. Let us hope for multiple reasons that Gerry is indeed her father, and that was not necessary.
I should add this: It's not usually impossible to obtain a known sample of a missing person's DNA. The family member I referred to in my OP who has done graduate work in the area of genetics was once assigned to obtain and sequence not one or two, but THREE samples of her known DNA from around her house. She was able to do it in short order - toothbrush, used tissue (this is not always the world's most pleasant job), and used bandage from a cut finger.
There is a scientist at the FSS named, I believe, Peter Gill, who has successfully obtained DNA samples from fingerprints. To my knowledge, FSS is the only lab in the world able to do this at present, but they have been doing it for a couple of years.
That is as about a clear an oversight as to what is happening with the evidence as I've read. Obviously, new questioning will be based around the latest DNA results and any inconsistencies in the time-line presented by the McCann's and friends. There may be a reconstruction, but someone at a UK university has supposedly already made a computer model of everyone's movements on the night, which may be used in the Dispatches program.
Everthing else is spuff.
