Alexei and Haemophilia

[J Kendrick]

Originally Posted by Anna was Franziska

I agree. There is no reason for anyone to lie. The conspiracy theories really have no point or basis.

As for not testing the sisters and mother for the gene, well, JK, somebody has to pay for all that work, maybe you can cough up the money since you seem to be the only one who has a problem with it.

This issue has absolutely nothing at all to do with any of your so-called "conspiracy theories".

This issue has absolutely everything to do with the still questionable identity of the blood disease that has been popularly claimed to have brought down a dynasty... which has never been proved by any form of scientific laboratory testing.

Now that the missing remains have been claimed to be found and identified, there can no longer be any excuses for not being able to prove the claims of history with every possible scientific test that is now available.

The question of cost cannot be an excuse either, given the large amounts of money, time, and labour that have already been exerted over the better part of the last two decades to find and identify those same missing remains.

The list of the products that are required for that very same laboratory testing for possible mutations in the Factor VIII gene and the costs of each of those products are well-known, as are the most efficient and cost-effective methods of screening for those mutations

As examples:
http://www.genelink.com/Literature/p...X%20Ver1.1.pdf
... and...
Detection of Factor VIII Gene Mutations by High-Resolution Melting Analysis -- Laurie et al. 53 (12): 2211 -- Clinical Chemistry

Until those still very necessary tests have finally been done to prove the existence of the blood disease that is claimed to have brought down the Russian monarchy... both the research... and the truth... will remain incomplete.

It is well past time that all of those experts who have been involved in this matter since the first of the bones were unearthed nearly 20 long years ago now step up to the plate and finish the job properly... by finally proving -- once and for all and with proper genetic laboratory testing -- whether or not the DNA evidence of that long-claimed blood disease had actually existed in the last of the Romanovs.

JK

[ottobre]

Genotype Analysis Identifies the Cause of the "Royal Disease" -- Rogaev et al., 10.1126/science.1180660 -- Science

Published Online October 8, 2009
Science DOI: 10.1126/science.1180660
Science Express Index

Brevia

Genotype Analysis Identifies the Cause of the "Royal Disease"

Evgeny I. Rogaev 1*, Anastasia P. Grigorenko 2, Gulnaz Faskhutdinova 3, Ellen L. W. Kittler 3, Yuri K. Moliaka 3
1 University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA.; Vavilov Institute of General Genetics RAS, Gubkina Street, 3, Moscow, 119991, RF.; Research Center of Mental Health RAMS, Moscow, 113152, RF.; Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119992, Moscow, RF.
2 University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA.; Vavilov Institute of General Genetics RAS, Gubkina Street, 3, Moscow, 119991, RF.; Research Center of Mental Health RAMS, Moscow, 113152, RF.
3 University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA.

* To whom correspondence should be addressed.
Evgeny I. Rogaev , E-mail: Evgeny.Rogaev@umassmed.edu


These authors contributed equally to this work.


The "royal disease," a blood disorder transmitted from Queen Victoria to European royal families, is a striking example of X-linked recessive inheritance. Although the disease is widely recognized to be a form of the blood-clotting disorder hemophilia, its molecular basis has never been identified, and the royal disease is now extinct. We identified the likely disease-causing mutation by applying genomic methodologies (multiplex target amplification and massively parallel sequencing) to historical specimens from the Romanov branch of the royal family. The mutation occurs in F9, a gene on the X chromosome that encodes blood coagulation Factor IX, and is predicted to alter RNA splicing and lead to production of a truncated form of Factor IX. Thus, the royal disease is the severe form of hemophilia, also known as hemophilia B or Christmas disease.

[Russophile]

I wanted to see why they called it "Christmas Disease" so I looked that up. It seems that Christmas disease is a FORM of hemophaelia but not the same, according to this article here.
Christmas Disease

[J Kendrick]

Originally Posted by Russophile

I wanted to see why they called it "Christmas Disease" so I looked that up. It seems that Christmas disease is a FORM of hemophaelia but not the same, according to this article here.
Christmas Disease

I'm not buying it... and here's why:

This latest study also now tells us...

They did *not* find any mutations in either the Factor VIII or Factor IX Gene.

From Genome Web Daily News:
Study Finds Hemophilia B-Causing Mutation in Russian Royal Remains | GenomeWeb Daily News | Sequencing | GenomeWeb
"The researchers did *not* find missense mutations, insertions, or deletions in any of the F8 or F9 gene sequences they tested. On the other hand, they did identify a substitution upstream of one of the F9 exons."

This sounds like they're just grabbing at straws to me.

and then... it goes on to say...

"Two members of the Romanov family carried this F9 mutation: Alexei was hemizygous for the mutation and one of his sisters, likely Anastasia, was a heterozygous carrier."

So, this means.. They *did* do tests on the earlier Ekaterinburg remains because they found part of their evidence in bones that were "probably Anastasia"... because we already know that they insist that the bone fragments from 2007 were probably Maria..

But here's the biggest flaw... This also means that there is *no evidence* in this study of any such mutations in the bones of
Alexandra... and it *must* be in Alexandra for their conclusions to be true.

There is also a major problem with claiming that it's Hemophilia B in Factor IX.. or Christmas disease... because Hemophilia B is seven times more rare than Hemophilia A and generally does not show up until adulthood.

Just to give you an example of how rare Hemophilia B really is, there are only 3300 cases in all of the US... out of 300 million people.

JK

[ottobre]

To avoid misunderstanding, please read the full text and supplementary information of the papers (Rogaev et al., 2009, PNAS and Science), the mutation in F9 gene was found in Alexandra first.

[J Kendrick]

Originally Posted by ottobre

To avoid misunderstanding, please read the full text and supplementary information of the papers (Rogaev et al., 2009, PNAS and Science), the mutation in F9 gene was found in Alexandra first.

Okay, then... What about this:

"Two members of the Romanov family carried this F9 mutation: Alexei was hemizygous for the mutation and one of his sisters, likely Anastasia, was a heterozygous carrier."

One of his sisters was a "heterozygous carrier"?

"Heterozygous" means that the sister had carried two copies of the mutation.. one from each parent...

But... Nicholas could not have been a carrier.

So, how do they explain that one?

JK

[kell]

because wasnt it from alix they inheriteed the mutated gene like every book says whom inheatited it from queen victoria

[Russophile]

Originally Posted by kell

because wasnt it from alix they inheriteed the mutated gene like every book says whom inheatited it from queen victoria

Kell, John is saying that the scientists say that "Anastasia" inherited from BOTH parents. Do you remember reading anything about Dagmar and Alex III being carriers? I don't.

[kell]

they had russ a differing muttation it was a melding of 2 genes if i recall and russ plz i have just wasnt sure which mutatetion he meant since both nicolhas his brothers had a type and so did his wife a differing type of gene mutation remember the test of 1991 bones they done a test which showed a differing gene type to mordern day dagmars reletives then to her own descandants thats all since it they both had a genetic mutations question is alix given her childern hemophillia nothing else i meant by it russ and russ the dagmar did pass a mutation to her childern which is diferrant then from the hemophillia gene mutation

[Russophile]

Kell can you give us some books or articles on this? Thanks!

[kell]

ok let me try this again some reason keeps booting me from posting 1st he had Heteroplasmy - Wikipedia, the free encyclopedia is also a genetic mutation which nicolhas got from his mother Mitochondrial DNA sequence heteroplasmy in the Grand Duke of Russia Georgij Romanov establishes the authenticity of the remains of Tsar Nicholas II - Nature Genetics Encyclopedia of genetics - Google Books CiteULike: Mitochondrial DNA sequence heteroplasmy in the Grand Duke of Russia Georgij Romanov establishes the authenticity of the remains of Tsar Nicholas II.
theres more but it i keep looseing my login and also nicolhas and alexandra documentray has somethings on this and warren might kill me for linking soo many urls

[Sonjapearl]

Reading Marsel's article on the "Christmas Disease" made me wonder about something. According to her article, Anastasia was the one with the hemophilia gene. But I remember reading some articles elsewhere that it was suspected Maria had it, because she once bled profusely when her tonsils were removed.

Is this more proof that the remains found recently were actually that of Alexei and Anastasia? It makes sense, those two were the smallest victims of the Bolshevik shooting.

Mods, forgive me if this is in the wrong thread.

[Marsel]

The haemophilia issue is discussed in this thread - Alexei and Haemophilia.

Even if Maria had been the one who was a carrier, she wouldn't suffer from the disease herself: in other words (unless there was some extremely rare mutation which affected her second X chromosome - and that could only be if she inherited mutation from both her parents), Maria wouldn't bleed, experience pain or anything else connected with haemophilia. If the carrier married and had sons, it is possible one of them would be affected. Her daughters could also be carriers like her.

[claypoint2]

Originally Posted by The O.C. Fanatic

Does anyone think that Alexei was never really a hemophiliac? I have never read no proof of the diagnosis or any medical reacords. The only formal statemate that I have read so far was by a physician of the Imperial court where the doctors described the boy's symptoms as a "significant anemia".

Originally Posted by Ex-Princess Lisa

Alexis was not a hemophiliac. He was being poisoned from the moment he was born.
Coumadin it is called in the USA, in the UK we call it Warfarin.

All the children were noted bleeders and Alix was always ill.

The palace was riddled with double agents.

Well, I guess that all the skeptics and conspiracy theorists are now confronted with scientific evidence that Alexei did, in fact, have haemophilia... and now we know which type (Haemophilia B). There are few scientific publications more prestigious and respected than the journal Science.

Of course, when a doubt or belief is sufficiently entrenched and persistent, mere scientific evidence won't suffice to dislodge it.... I have just read some of the ongoing conversation here, and I'll confess to being amazed by people who believe that they have more knowledge about genetics -- and that they are in a better position to evaluate the evidence -- than the folks on the editorial board of Science.

For the record (post #143), to say that Christmas Disease is a "form" of haemophilia is exactly the same as saying that it is a "type" of haemophilia (type B, in fact). Haemophilia -- like so many other diseases (e.g., hepatitis) is not a unitary thing; there are multiple variants, but they are all constitute the disorder. In other words, Christmas Disease IS haemophilia.

[Russophile]

I'm quoting the article claypoint. Do you have a degree in genetics, by chance?

Kell, Warren actually might HELP you to bundle the urls in and make your posts more clear. He is actually here to help.

[claypoint2]

Originally Posted by Russophile

I'm quoting the article claypoint. Do you have a degree in genetics, by chance?

No, I don't.... do you? The fact that I don't have an advanced degree in genetics is precisely why I don't feel qualified to challenge the findings and interpretations of those who wrote the paper published in the prestigious journal Science. I, for one, continue to marvel at those who feel able to do so without holding the relevant credentials. For the record, these articles are subject to an exhaustive peer-review process before they are accepted for publication, and I would be very cautious about challenging them unless I were expert in the field.

Although it's quite beside the point, since you asked about credentials I will offer that I have two doctorates (one of them a Ph.D.), have worked in hospitals for many years, and hold a faculty appointment at the medical school of a university you may have heard of. A child of mine has done research on the genetics of leukemic tumors at a lab associated with the same university... and I certainly don't feel qualified to challenge the findings published in Science.

Incidentally, in your post above (#153) you say that you were quoting the article Christmas Disease when you stated that Christmas Disease is "not the same" as haemophilia (#143). I see nothing in that link to support your statement.

[Alison20]

Having just stumbled on this thread, I am extremely surprised that there are people who feel so vehemently that Alexei should not have haemophelia.

It seems to fly in the face of logic and all the first hand reports relating to all the descendents of Q V who had similar physical problems.

This report now seems very detailed and scientific - but, then, those who have a need for a conspiracy will have closed minds (President Kennedy and Princess Diana are cases where there has been a lot of mileage expended to try to show that the simple truth was not the truth!). :-)

[Russophile]

Originally Posted by claypoint2

No, I don't.... do you?

Well bummer since it can prove very helpful in this thread.

Originally Posted by claypoint2

Incidentally, in your post above (#153) you say that you were quoting the article Christmas Disease when you stated that Christmas Disease is "not the same" as haemophilia (#143). I see nothing in that link to support your statement.

Then I apologize.

[claypoint2]

Originally Posted by Alison20

Having just stumbled on this thread, I am extremely surprised that there are people who feel so vehemently that Alexei should not have haemophelia.

It seems to fly in the face of logic and all the first hand reports relating to all the descendents of Q V who had similar physical problems.

This report now seems very detailed and scientific - but, then, those who have a need for a conspiracy will have closed minds (President Kennedy and Princess Diana are cases where there has been a lot of mileage expended to try to show that the simple truth was not the truth!). :-)

Well said, Alison. I couldn't agree more.

[claypoint2]

Originally Posted by Russophile

Then I apologize.

No worries! That's what these forums are for; hopefully we all gain knowledge and clarity through the back-and-forth of conversation.