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Posted 27 December 2000 - 04:11 PM

About 15-20% of Armenians have the recessive genes for this disease and if you get a set from both of your parents
you are afflicted. Very hard to diagnose if you don't know about it, very easy to treat when diagnosed.

Several thousand years ago, somewhere in the Middle East, there lived a person who bequeathed a particular gene to
many present-day descendants. But these millions of now distant relatives could not convincingly be called one big
happy family. They include Jews, Arabs, Turks and Armenians.

The gene, a variant of a gene that controls fever, has come to light because it causes an unusual disease called familial
Mediterranean fever in individuals who inherit a copy from both parents. The gene's presence among a surprising
group of populations hints at the rich archeology that lies buried in the human genome, once geneticists and historians
have learned how to interpret it.

Two rival teams of scientists in France and the United States have been racing to isolate the gene for a year. The race
finished on Friday, with the American team announcing its finding in the journal Cell, the French team in Nature
Genetics.

The American team has named the gene pyrin, from the Greek word for fire, after its role in fever; the French team calls
it marenostrin after the Latin "Our Sea," a Roman phrase for the Mediterranean. The race could be considered a dead
heat, although the American team has recovered the whole gene, the French team just a major portion.

People who inherit a single variant copy of the fever gene from one parent and a normal copy from the other parent
have no sign of the disease. They are so numerous, constituting up to 20 percent of certain Jewish and Armenian
populations, that carrying one copy is assumed to confer some significant benefit, like a greater resistance to disease.

In individuals with two copies, however, the immune system goes into overdrive at inappropriate moments, causing
bouts of severe fever. The scientists who have analyzed the fever gene and its variants say they now understand why.

The normal gene specifies a protein that from its designmotifs looks as if it is meant to slip into the nucleus of the cell
and switch genes on or off. Since the gene is active only in a special class of white blood cells, its usual duty seems to
be to control the cells' activity and rein them in when the threat of infection has passed. The white blood cells defend
against infections and often cause fever in doing so.

The new findings, in portraying the exact genetic anatomy of the normal gene and its variant forms, give a strong clue
as to why the variant versions have the effects they do. The variant forms have mutations, or changes of a single DNA
letter, in the region of the gene assigned to the switching function. Presumably the mutations make the gene's protein
inefficient in its duty of restraining the white blood cells.

The historical significance of the finding lies in the genetic relationship it implies between populations that have been
separate for many hundreds of years. For example, the variant form of the gene found in North African Jews, Iraqi
Jews and Armenians is the same, carrying both the same mutation and a pattern of 11 other genetic changes, all
harmless.

Although single genetic changes can arise independently, the presence of so many together in the same combination
points strongly to a "founder" or single ancestor as the original source of the variant gene.

A second variant form of the gene, according to the American team, is shared by Iraqi Jews, Ashkenazi Jews, the
Moslem Druze sect and Armenians. The two variants are similar and probably derive from the same founder.

The Americans write that the mutations are "very old" and that they suggest "common origins for several Middle
Eastern populations."

Dr. Daniel Kastner, a member of the team, said the original possessor of the variant gene probably lived several
thousand years ago and certainly less than 40,000 years ago, according to a formula that relates the average length of a
shared genetic segment to the number of generations that have passed. Kastner said the founder's gene may have
spread through a population in the Middle East that existed before Jews, Armenians and Arabs became distinct peoples.

He also noted that the variant fever gene established a common genetic lineage between Ashkenazi Jews and Iraqi Jews,
even though the two communities have been separated since the Babylonian Captivity that began in 597 B.C. Many
Jews from the ancient community in Iraq now live in Israel.

The French team has detected the main variant in Jews and Arabs from North Africa and in Turks and Armenians. Dr.
Jean Weissenbach of the gene laboratory Genethon, a member of the French team, said that the variant gene was
ancient but that an exact date of it origin could not be calculated.

Experts in Middle Eastern history and linguistics said they knew of no historical event to link the four populations in
which the variant fever gene has been found, although three - Arabs, Jews and Armenians - are related geographically,
having originated in the Middle East. The ancestral Armenian homeland is around Lake Van in Turkey. The Seljuk
Turks invaded from Central Asia in the 11th century, and they absorbed many of the local inhabitants.

Familial Mediterranean fever is rare in the United States. Patients often endure years of misdiagnoses. Once the disease
is recognized, an effective drug, colchicine, is available. Now that the DNA sequence of the variant gene is known, an
accurate test can be made.

The American-led team includes scientists from laboratories in Israel and Australia. The French team is from Genethon
in Evry and two other laboratories in France.


The New England Journal of Medicine -- April 2, 1998 -- Volume 338,Number 14

Familial Mediterranean Fever Gene

To the Editor:

Babior and Matzner (Nov. 20 issue) (1) state that the recently identified familial Mediterranean fever (FMF) gene (2,3)
can be used to establish the diagnosis of this disease. However, the penetrance of the four described mutations is not
known, and patients with pyrin, or marenostrin, mutations affecting only a single allele will remain a diagnostic
challenge, as illustrated by the following case report.

Recurrent fever, abdominal pain, and pleural effusions developed in a 27-year-old Armenian man. Plasma C-reactive
protein concentrations exceeded 100 mg per liter during the attacks but on other occasions were normal (<10 mg per
liter). The results of numerous investigations were nondiagnostic, and the patient’s symptoms responded partially to
colchicine therapy. DNA analysis revealed that he was heterozygous for the Met694Val ("Med") (2) FMF mutation.

However, continued fever, pleurisy, and radiographic changes suggested a diagnosis of pulmonary tuberculosis, which
was confirmed bacteriologically.  The patient's entire clinical course could be explained on the basis of tuberculosis
infection and reactivation, whereas the clinical significance of his FMF mutation remains unclear.

Familial Mediterranean fever is an autosomal recessive disease carried by one in seven Armenians. (4) The four
described mutations in the pyrin gene occur in only 85 percent of carriers of familial Mediterranean fever chromosomes,
(2) and therefore, there may be other unidentified mutations or other factors able to promote the expression of the
disease in patients with mutations affecting a single allele. Alternatively, some mutations may be dominant. These
points are highlighted by the case of another patient of ours with long-standing classic familial Mediterranean fever in
whom we have also identified a Met694Val mutation in only a single allele.

It is possible that features of the disease can develop in carriers of familial Mediterranean fever under certain
circumstances. The absence of any identifiable mutation makes the diagnosis of familial Mediterranean fever unlikely,
but the clinical significance of pyrin mutations affecting only a single allele is not yet clear.

Alison H. Holmes, M.D.
David R. Booth, Ph.D.
Philip N. Hawkins, F.R.C.P.
Hammersmith Hospital
London W12 0NN, United Kingdom

References
1. Babior BM, Matzner Y. The familial Mediterranean fever gene-cloned at last. N Engl J Med 1997;337:1548-9.

2. The French FMF Consortium. A candidate gene for familial Mediterranean fever.  Nat Genet 1997;17:25-31.

3. Balow JE Jr, Shelton DA, Orsborn A, et al. A high-resolution genetic map of the familial Mediterranean fever
candidate region allows identification of haplotype-sharing among ethnic groups. Genomics 1997;44:280-91.

4. Rogers DB, Shohat M, Petersen GM, et al. Familial Mediterranean fever in Armenians: autosomal recessive
inheritance with high gene frequency. Am J Med Genet 1989;34:168-72.

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Posted 27 December 2000 - 06:53 PM

quote:
Originally posted by Kazza:

Several thousand years ago, somewhere in the Middle East, there lived a person who bequeathed a particular gene to
many present-day descendants. But these millions of now distant relatives could not convincingly be called one big
happy family. They include Jews, Arabs, Turks and Armenians.


Kazza jan, thank you very much. That was a very important info. Note that even their reaserch proved the circulation of this desease amoung Jews, Arabs, Turks and Armenians, they doubt that this is a valid point to claim the initial ethnic relation between these 4 nations. Because there is a trend among some pseudo-scientists to do so.

[This message has been edited by Berj (edited December 27, 2000).]

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Posted 27 December 2000 - 06:59 PM

Berj jan youre welcome any time. I just thought it was a thing that people here wanted to talk about, I certainly want to now more about what you think. I did that on purpose to actually point out the ethnic ties between these groups!!

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Posted 28 December 2000 - 02:51 AM

Kazza jan, my understanding of the quote I included in my previous entry was wrong (I missed the word "happy"). They actually try to prove the ethnic ties between Jews, Arabs, Turks and Armenians.

In my opinion, even if this disease is common among this 4 nations, it proves only one thing: we are all mixed to some degree. Well, nobody doubts that. At present, DNA ties among this four groups can be proved by:

Armenian-Jewish case: the resettlement of Jews to some areas around Lake Van by king Tigran the Great after his southern campaign and their assimilation with the local population. Armenian and Jewish communities in Crimea from 13th century to present days etc.

Armenian-Arab case: Arabic invasions in 7th-10th centuries. Adoption of Armenian children by Syrian Arabs in Der Zor desert area after the Genocide.

Armenian-Turkish case: Turkic invasions from 11th century onward. Enforcement of the Turkic language of Seljuk-Ottoman minority on the nations of Ottoman Empire.

But this does not prove that the tribes which formed the Armenian, Jewish, Arabic and Turkish nations once lived compactly in one area.

There certainly are strong ethnic ties between the Arabs and the Jews, as obvious as strong ethnic ties between the Armenians and the Persians. Their ethnic ties are even stronger than our's with Persians. But the territorial bases from where this nations spread after their formation are different.

Arabs and Jews: Arabic Peninsular

Armenians: the plateaus stretching from present southern Turkey to north India

Turks: Altay region in Central Asia

The movement of tribes (note: not the conquerors such as Alexander the Great, Arabs after the adoption of Islam etc.), as Arabic Qureishies, proto-Armenian Indo-Europeans, Turkic Seljucs, Oghouses, Ottomans has always been from South-East to North-West. The reason for that is that for a long time after the Ice Period the climate on the Eurasian continent had been getting warmer moving to the north. So the fertile lands of the Ice Period had been turning to deserts (Arabic Peninsular) and burned down grasslands (Mongolia for instance) while the cold European, north Mediterranean territories turned to fertile lands. However the lands of India and China, though located on the south and east of Eurasia, remained in excellent condition due to their close location to the sea. For this reason they have areas of extensive agriculture in India and China located by the sea as in the cases of oasis in Arabic Peninsular. Some of these oasises in Arabic Peninsular are near to the sea and the others are getting fueled by underground waters. Note that the inland areas of India and China are not that good for agriculture in case if there are no big rivers like Indra, Ganga, Huanhe or Yangtse. The only river in around Arabic Penninsular area, which gave birth to the Egyptian civilization is the Nile. In Mongolia's case, at present they have 2 mil. population on a territory equal to the half of Europe.

IN SEARCH OF MORE FOOD, all these tribes moved to north-west. But before these movements and resettlements, they lived isolated from each other due to the poor communication means (for example the absence of wheels in the times these tribes where still in formation period) and terrain difficulties like huge mountain ranges and the Caspian Sea between Central Asia and the Armenian and Iranian plateaus.

So it is very difficult to find any facts of historic ethnic relation between the proto-Armenian, proto-Jewish-Arab and proto-Turkic tribes.To prove there was no relation is much easier.

The definition of a "present day Turks" and "historic Turks" must be different in scientific researches.

And also, this removes the base of the hypothesis that Armenians moved to the Armenian plateau from Europe(the Balkans). We would never move from there to this stone jungle.

[This message has been edited by Berj (edited December 28, 2000).]

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Posted 06 January 2001 - 05:28 AM

I think you're a little bit wrong Berj jan.
Yes,there are no ethnic ties between Armenians and Turks.They really came from far East Asia.
BUT!!!It may sound weird but we do have anciet ethnic ties with Jews and Arabs.
Jews and Arabs are basically as close ethnically as Russians and Ukranians,the only difference is religion!They have the same Semite ancestors of course.Well some of those Semite tribes formed our Nation later.They migrated to the Armenian plateuo.
There were lots of them:Aramiis,Hettis,Huuritians,Finicians.
when they came to our land they mixed with the local big tribe called Hayasa-Azzi.That is how Armenians were created.The world started to call us by the name of the bigest invador tribe -Aramiis(Armenian!)And we still call ourselves by the name of our local tribe - Hayasa(Hayer).
That's why we have the same genes as Jews and Arabs.I think Turks didn't mix much with us because there were almost no marriages and most of our women commited "honour Suicides" if they were raped.But a lot of Turks married Arabs so they could get it this way.

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Posted 06 January 2001 - 09:24 AM

Nvard jan, Hettis, Hurits and Finicians were not Semit tribes. However Arameas were a Semit tribe. The formation of our as well as all other nations in this world is a very complicated issue no one can ever solve.

If we generalise this way, all people in this world are very mixed. Each and every one. And we have the same amount of Turik blood as they have ours.

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Posted 08 January 2001 - 04:48 AM

WHATEVER!!

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Posted 08 January 2001 - 08:10 AM

Utttem! Ov uni senc Nvard?

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Posted 10 January 2001 - 04:50 AM

Hahahahahahahahahahahaha




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