Alexei and Haemophilia

[J Kendrick]

Originally Posted by Elspeth

Why would it rule out that she was a carrier? If the mutation could have happened in her son, why could it not have happened in her father? As well as the Russian royal family, haemophilia seems to have afflicted the Spanish royal family, and Leopold wasn't an ancestor of that family.

Those same questions are precisely why the hemophilia story is flawed.

Victoria's father was not a hemophiliac... and that was the whole point of the 1995 book "Queen Victoria's Gene', in which the authors had questioned Victoria's parentage and suggested that she may have been illegitimately fathered by another man who must have been a hemophiliac... as the only way to explain how Victoria could have passed on the gene (as has been popularly claimed but has still not been scientifically proved).

Recent research shows how hemophilia starts in a family by either a gene inversion or the phenomenon now known as "jumping DNA" in the first boy to have the disease... not in the mother... which in Victoria's case was her fourth of four sons. If the disease can only start in the first son to have it... which in Victoria's case is Leopold... and not in his mother... then she cannot be a carrier and cannot pass on the faulty gene to her daughters because she does not have the faulty gene. She cannot be the first to have the faulty gene if the recent research shows that the DNA flaws that initially cause the disease originate almost "exclusively in male germ cells"

For this reason, among numerous others, somewhere in Queen Victoria's line the disease must have been misdiagnosed... because the currently known facts of recent DNA research into the way that hemophilia starts do not fit well at all with the way that the story has always been told.

JK

[Elspeth]

Originally Posted by J Kendrick

Those same questions are precisely why the hemophilia story is flawed.

Victoria's father was not a hemophiliac... and that was the whole point of the 1995 book "Queen Victoria's Gene', in which the authors had questioned Victoria's parentage and suggested that she may have been illegitimately fathered by another man who must have been a hemophiliac... as the only way to explain how Victoria could have passed on the gene (as has been popularly claimed but has still not been scientifically proved).

Recent research shows how hemophilia starts in a family by either a gene inversion or the phenomenon now known as "jumping DNA" in the first boy to have the disease... not in the mother... which in Victoria's case was her fourth of four sons. If the disease can only start in the first son to have it... which in Victoria's case is Leopold... and not in his mother... then she cannot be a carrier and cannot pass on the faulty gene to her daughters because she does not have the faulty gene. She cannot be the first to have the faulty gene if the recent research shows that the DNA flaws that initially cause the disease originate almost "exclusively in male germ cells"

For this reason, among numerous others, somewhere in Queen Victoria's line the disease must have been misdiagnosed... because the currently known facts of recent DNA research into the way that hemophilia starts do not fit well at all with the way that the story has always been told.

JK

So you're saying that the haemophilia in the Spanish royal family wasn't haemophilia regardless of the doctors who said it was, that the haemophilia in the Russian royal family wasn't haemophilia regardless of the doctors who said it was, and that the haemophilia in one of Princess Alice's sons wasn't haemophilia regardless of the doctors who said it was.

While I don't have a great deal of confidence in the "Queen Victoria's Gene" book (I was using it last year when I had to do some technical writing about major genetic and infectious diseases and I wasn't wildly impressed by it), I think the notion that Queen Victoria's actual father was an unknown haemophiliac is every bit as likely as the notion that haemophilia has been misdiagnosed in three royal families.

Oh, and by the way, when they say something happens almost excusively in male germ cells, the ethical way to do your highlighting is as follows:

"happens almost excusively in male germ cells" not "happens almost excusively in male germ cells."

Just sayin'...

However, if we're going to resort to argument based on trading quotes from newspaper articles, then I'll add some emphasis to a quote which you apparently thought wasn't worth emphasising.

"In her case, it caused no problem. Kazazian said he suspected that the line1 element jumped from her Chromosome 22 to the X chromosome either in the mother's egg cell or during an early stage in the development of the embryo that became the boy."

That, right there, ought to give a clue that "almost exclusively in male germ cells" (wherever you want to put your emphasis) is by no means the whole story.

First, the article which refers to it is nearly 15 years old, so if it was true that haemophilia in general only originates in men, I think it would have worked through to being common knowledge by now. However, that paper doesn't refer to haemophilia in general, it refers to the specific case of haemophilia caused by inversions in the Factor VIII gene. That's actually a different process from the one in the newspaper article, which is a migration of genetic material from one chromosome to another. Also, the paper states quite clearly that the gene inversion process accounts for only around half of all cases of this particular type of Factor VIII-related severe haemophilia; not only that, but Factor VIII isn't the only clotting factor whose defects result in haemophilia.

So what we have here is an example of inductive reasoning run wild - "this is how it is for a minority of cases so therefore this is how it must be for all cases and certainly for this case." Before falling back on the "almost exclusively" argument - or, in your case, the "almost exclusively" argument - you'd need to show that the haemophilia in Prince Leopold's family was due to this sort of inversion in the Factor VIII gene, which as far as I can tell, you haven't. And the supporting evidence for more widespread haemophilia in the Russian and Spanish royal families as well as in one of Princess Alice of Hesse's sons suggests that this particular piece of inductive reasoning is, to say the least, seriously flawed.

[Russophile]

Originally Posted by Anna was Franziska

But really, I doubt that anyone but Tammet supporters have ever questioned the hemophilia diagnosis, or care to find out if it was proven, so it may be unlikely they're going to bother with it.

On the contrary, I haven't read or done much research about Tammet at all and am certainly not a suporter, yet I find the discussion on the haemphilia gene quite fascinating.
Quite frankly, I would like to know more.

[Camilo2002]

In my opinion there is no doubt it was hemophilia.

Nowadays, a 7th generation descendant of Queen Victoria is suffering from Hemophilia. Ferdinand Soltmann, whose mother is descended from Queen Victoria twice paternally (via the Queen's children Alice and Alfred). It has been proved that Ferdinand suffers from hemophilia, as a result I would think that this fact demonstrates that Alexei was a hemophiliac. After all these years the sickness reappears, it seems that when 2 gene carriers procreate Hemophilia is likely to reappear. The 2 genealogic lines of Ferdinand Soltmann that descend from Queen Victoria are the following:

1. QUEEN VICTORIA-> PRINCESS ALICE OF THE UK-> PRINCESS VICTORIA OF HESSE-> PRINCESS ALICE OF BATTENBERG -> PRINCESS MARGARITA OF GREECE ->

-> KRAFT, 9TH PRINCE OF HOHENLOHE-LANGEBURG -> PRINCESS XENIA OF HOHENLOHE-LAGENBURG -> FERDINAND SOLTMANN


2. QUEEN VICTORIA-> PRINCE ALFRED OF SAXE-COBURG-GOTHA->PRINCESS ALEXANDRA OF EDIMBURGH->GOTFRIED, 8TH PRINCE OF HOHENLOHE-LAGENBURG->

-> KRAFT, 9TH PRINCE OF HOHENLOHE-LAGENBURG -> PRINCESS XENIA OF HOHENLOHE-LANGEBURG -> FERDINAND SOLTMANN.

[fearghas]

It is possible that Prince Kraft inherited the gene fron his mother but Was Prince Kraft of Hohenlohe haemophiliac? If he wasn't then he couldn't have passed the gene onto his daughter, there fore Ferdinand doesn't have QVs.version of the disease. Princess Xenia might have inherited it from her mother, again that would mean it was not QVs version. Or it might have been another spontaneous mutation.
As QVs son, Prince Alfred was not haemophiliac he didn't pass the gene on.

[Warren]

Originally Posted by fearghas

...Princess Xenia might have inherited it from her mother...

Xenia's mother is Princess Charlotte, daughter of Prince Alexander of Croÿ (Austrian Branch) and Anne Campbell (born in the UK).

[Camilo2002]

Originally Posted by fearghas

It is possible that Prince Kraft inherited the gene fron his mother but Was Prince Kraft of Hohenlohe haemophiliac? If he wasn't then he couldn't have passed the gene onto his daughter, there fore Ferdinand doesn't have QVs.version of the disease. Princess Xenia might have inherited it from her mother, again that would mean it was not QVs version. Or it might have been another spontaneous mutation.
As QVs son, Prince Alfred was not haemophiliac he didn't pass the gene on.

Xenia's father, Prince Kraft, had some clotting issues, which led the family to believe he may have been a mild hemophiliac. Probably the fact that both Kraft's parents were QV descendants was a factor in this reappearance of the sickness.

Some scientists considered that hemophilia might have been latent in the Saxe-Coburg family and the fact that Queen Victoria married her maternal first cousin provoked an "spontaneous mutation" which resulted in the sickness being passed on to many of their descendants.

Neither Queen Victoria's parents nor grandparents were hemophiliacs, as a result nobody can be sure on how did the sickness appear. Some people investigated in order to find out if it was possible that QV was the result of an extramarital relationship of her mother the Duchess of Kent, Victoria of Saxe-Coburg-Gotha; however, given other factors like lack of evidence and the strong similarity of Queen Victoria and her paternal relatives like her first cousin, Princess Mary of Cambridge "fat Mary" most researchers decided against the "lover's theory".

In my opinion, the bloodline from QV to Ferdinand Soltmann demonstrates that the sickness suffered by QV descendants was hemophilia. QV's daughters, princesses Alice and Beatrix, were very strong in passing the sickness on to their descendants in the German, Russian and Spanish royal families.

The way the sickness reappeared in the Queen's family remains a mistery.

[Anna was Franziska]

Here is Dr. Coble's answer to the hemophilia question:

For the hemophilia - I was asked by the Russians to look into the
possibility of testing for the gene, but in the end, we found this to be
too challenging for several reasons.

(1) We had limited material to work with - only a couple of grams of
bone powder.

(2) No one is absolutely sure (to my knowledge) that Queen Victoria
passed Hemophilia A (factor VIII deficiency) or Hemophilia B (factor IX
deficiency) to her descendants - so both of these genes would require
sequencing if HA was negative.

(3) The factor VIII gene is quite large with 26 exons - this would
require a great deal of sequencing of nuclear DNA, and likely consume
the entire sample. Note that we did have samples from the Tsarina -
however, these were in less quantity that the samples from Grave 2 since
those remains are now at rest in St. Petersburg.

(4) Unlike other diseases, such as Sickle Cell Anemia - where a
well-characterized single nucleotide base change causes an amino acid
change to create the "sickle" phenotype of the disease, Hemophilia A
could be caused by hundreds of different mutations including single
nucleotide substitutions, deletions, insertions, and a common
translocation of one of the exons to the opposite end of the
X-chromosome. In other words, we can't pinpoint from the beginning
where to look for the mutation. This required sequencing step by step
from the beginning until the end of the gene.

(5) We considered finding a living relative that either has the disease
(none exist) or, a carrier female for testing. The media company spoke
with a Princess from Spain who unfortunately lost a son from a suspected
"blood disorder" in the 1960s. From what I understand, she told the
media company that she was tested for the disease, and is not a carrier.


(6) Finally, we decided to focus on what we do best: recovering forensic
loci. We felt that if we could develop a complete (or near complete)
profile from the evidence, then the statistics would provide us with a
powerful amount of discrimination. Going from a Likelihood Ratio in the
trillions to a number in the quad- or quintrillions (by trying to find
the Hemophilia gene) seemed like a lot of effort to go from one big
number to another big number - while consuming all of the evidence along
the way.

[AnastasiaEvidence]

Originally Posted by Russophile

On the contrary, I haven't read or done much research about Tammet at all and am certainly not a suporter, yet I find the discussion on the haemphilia gene quite fascinating.
Quite frankly, I would like to know more.

tsarevich_alexei
Kendrick's website about Tammet the Alexei claiment.

Some scientists considered that hemophilia might have been latent in the Saxe-Coburg family and the fact that Queen Victoria married her maternal first cousin provoked an "spontaneous mutation" which resulted in the sickness being passed on to many of their descendants.

This is highly possible because back then many people would marry their cousins and their children would carry many different illnesses. Very good point.

[fearghas]

Originally Posted by Camilo2002

Probably the fact that both Kraft's parents were QV descendants was a factor in this reappearance of the sickness.

Not for the Haemophilia. For a heriditary disease to be caused, spread or intisified by inbreeding, then both parents of the afflicted child must be carrying the genes responsible. Prince Alfred, who was the ancestor of Prince Krafts father did not have haemophilia, therefore he could not have passed it on. So in this case the fact that Prince Krafts parents were related had nothing to do with the possiblility of Haemophilia appearing in their son or great grandson. As I keep saying, haemophilia in the royal families was not spread by inbreeding. Those who inherited the disease would most likely have done so, regardless of who their fathers may have been.

[J Kendrick]

Originally Posted by Anna was Franziska

Here is Dr. Coble's answer to the hemophilia question:

(2) No one is absolutely sure (to my knowledge) that Queen Victoria passed Hemophilia A (factor VIII deficiency) or Hemophilia B (factor IX deficiency) to her descendants
-----------
(5) We considered finding a living relative that either has the disease (none exist) or, a carrier female for testing. The media company spoke with a Princess from Spain who unfortunately lost a son from a suspected "blood disorder"in the 1960s. From what I understand, she told the media company that she was tested for the disease, and is not a carrier.

Translation: There's *still* no genetic proof whatsoever of the suspected existence of the disease in any of the members of the Russian Imperial family.

In response to the quotes that have been credited to Dr. Coble in the previous post, one is now prompted to ask: Exactly which "media company" is it that Dr. Coble is referring to here, and precisely what part did they play in this latest investigation and why?

JK
See: American Journal of Hematology
Wiley InterScience :: Session Cookies

[J Kendrick]

Originally Posted by Elspeth

If we're going to resort to argument based on trading quotes from newspaper articles, then I'll add some emphasis to a quote which you apparently thought wasn't worth emphasising.

"In her case, it caused no problem. Kazazian said he suspected that the line1 element jumped from her Chromosome 22 to the X chromosome either in the mother's egg cell or during an early stage in the development of the embryo that became the boy."

That, right there, ought to give a clue that "almost exclusively in male germ cells" (wherever you want to put your emphasis) is by no means the whole story.

DNA elements jumping from a very different chromosome to the X- chromosome in the mother's egg cell to later cause a blood disease in the birth of a son *still* does not make the mother a carrier. The problem is not in the mother's own X-chromosome. The problem then only exists in that one individual egg cell that then later becomes her son.

While a son may well be born with a disease in this manner that is now known as "jumping DNA", it has not been inherited. His mother is still not a carrier... and his sisters, therefore, will not be carriers either.

JK

[Anna was Franziska]

JK, what difference does it make what caused the boys to bleed, as long as we have a positive ID on the body of Alexei and know he died with his family?

[J Kendrick]

Originally Posted by Anna was Franziska

JK, what difference does it make what caused the boys to bleed, as long as we have a positive ID on the body of Alexei and know he died with his family?

Just as I had said to you on this same thread last week... This issue is not about the question of identification.

This is all about the very real opportunity that now exists that can finally allow us to confirm -- once and for all and with solid scientific evidence -- whether or not the historically popular but *still totally unproven* claim that a blood disease had brought down the House of Romanov is... or is not... actually true.

JK

[Elspeth]

Originally Posted by J Kendrick

DNA elements jumping from a very different chromosome to the X- chromosome in the mother's egg cell to later cause a blood disease in the birth of a son *still* does not make the mother a carrier. The problem is not in the mother's own X-chromosome. The problem then only exists in that one individual egg cell that then later becomes her son.

Why would the problem not be in her own X chromosome? Are you saying that the migration only occurs in the X chromosome of one of the egg cells she carries, not in her own X chromosome? Could you give some backup information to support that?

[Anna was Franziska]

Originally Posted by J Kendrick

This is all about the very real opportunity that now exists that can finally allow us to confirm -- once and for all and with solid scientific evidence -- whether or not the historically popular but *still totally unproven* claim that a blood disease had brought down the House of Romanov is... or is not... actually true.

JK

Whatever made him bleed DID bring help down the dynasty, because of the influence of Rasputin on Alexandra. I believe it was hemophilia, but even if it wasn't, it makes no difference as far as Alexei's illness causing problems that helped the revolutionaries overthrow the government, so history would not change there.

As far as confirming it, Dr. Coble has already explained why testing for the faulty gene was impossible.

[J Kendrick]

Originally Posted by Anna was Franziska

Whatever made him bleed DID bring help down the dynasty, because of the influence of Rasputin on Alexandra. I believe it was hemophilia, but even if it wasn't, it makes no difference as far as Alexei's illness causing problems that helped the revolutionaries overthrow the government, so history would not change there.

As far as confirming it, Dr. Coble has already explained why testing for the faulty gene was impossible.

Difficult, yes, but *not* impossible.

The fact still remains... even in spite of the claimed results from those fragments uncovered in the Summer of 2007... there is still no scientific proof whatsoever of the suspected existence of haemophilia in the Russian Imperial family.

JK

[J Kendrick]

Originally Posted by Elspeth

Are you saying that the migration only occurs in the X chromosome of one of the egg cells she carries, not in her own X chromosome? Could you give some backup information to support that?

Precisely.

Read the quote again: "In her case, it caused no problem. Kazazian said he suspected that the line 1 element jumped from her Chromosome 22 to the X chromosome either in the mother's egg cell or during an early stage in the development of the embryo that became the boy."

The problem appears first in the egg. Not in the chicken.

JK

[Elspeth]

We're into inductive reasoning again. In the particular case you're referring to, it says clearly that the genetic sequence in question was on the woman's chromosome 22, so the transfer occurred in an egg cell or during development of the boy's embryo.

However, if there's something in that article which states that this is the only possible scenario for this sort of transfer in general (as opposed to being the scenario in this case), feel free to point it out.

Why are you so sure that in other cases it's impossible for the transfer to occur during development of a female embryo, thus making her a carrier? And don't start with the "almost exclusively in males" stuff, because that refers to inversions, not transfers.

[J Kendrick]

Originally Posted by Elspeth

Why are you so sure that in other cases it's impossible for the transfer to occur during development of a female embryo, thus making her a carrier? And don't start with the "almost exclusively in males" stuff, because that refers to inversions, not transfers.

Of course it may happen in the development a female embryo, but that would then greatly reduce the odds of it happening to a far smaller number than three daughters in five, as it is now claimed in Victoria's case.

.. and Victoria still would not be a carrier.