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The Two Common Mutations Causing Factor XI Deficiency in Jews Stem
From Distinct Founders: One of Ancient Middle Eastern Origin
and Another of More Recent European Origin
By Hava Peretz, Avital Mulai, Sali Usher, Ariella Zivelin, Avihai Segal, Zahavi Weisman, Moshe Mittelman,
Hannah Lupo, Naomi Lanir, Benjamin Brenner, Ofer Shpilberg, and Uri Seligsohn
Previous studies showed that factor XI (FXI) deficiency commonly observed in Ashkenazi Jews is caused by two similarly frequent mutations, type II (Glu117stop) and type III
(Phe283Leu) with allele frequencies of 0.0217 and 0.0254,
respectively. In Iraqi Jews, who represent the ancient gene
pool of Jews, only the type II mutation was observed with an
allele frequency of 0.0167. In this study we sought founder
effects for each mutation by examination of four FXI gene
polymorphisms enabling haplotype analysis in affected Jewish patients of Ashkenazi, Iraqi, and other origins and in Arab
patients. Initial population surveys of 387 Middle Eastern
Jews (excluding Iraqi Jews), 560 North African/Sephardic
Jews, and 382 Arabs revealed allele frequencies for the type
II mutation of 0.0026, 0.0027, and 0.0065, respectively. In
contrast, the type III mutation was not detected in any of
these populations. All 60 independent chromosomes bear-
ing the type III mutation were solely observed in Ashkenazi
Jewish patients and were characterized by a relatively rare
haplotype. All 103 independent chromosomes bearing the
type II mutation in patients of Ashkenazi, Iraqi, Yemenite,
Syrian, and Moroccan Jewish origin and of Arab origin were
characterized by another distinct haplotype that was rare
among normal Ashkenazi Jewish, Iraqi Jewish, and Arab
chromosomes. These findings constitute the first example
of a mutation common to Ashkenazi Jews, non-Ashkenazi
Jews, and Arabs and are consistent with the origin of type
II mutation in a founder before the divergence of the major
segments of Jews. Our findings also indicate that the type
III mutation arose more recently in an Ashkenazi Jewish
individual.
q 1997 by The American Society of Hematology.
C
fewer episodes of injury-related bleeding.13 Recently, we
described another mutation in an Ashkenazi Jewish patient
and designated it type IV mutation. It involves a 14 bp
deletion at the exon 14/intron N junction of the FXI gene.14
A survey of 125 unrelated Ashkenazi Jewish patients with
major FXI deficiency showed that type II and type III mutations were the predominant mutations in this ethnic group,
each accounting for 49.2% of the mutant alleles. The frequency of type I and type IV mutations was only 1.2% and
0.4%, respectively.5
In recent years we observed several families of Iraqi Jewish and Arab origin with members affected by FXI deficiency
that was caused by the type II mutation.13,15 A survey of the
type II and type III mutations in Ashkenazi and Iraqi Jews
residing in Israel revealed that the type II mutation is as
frequent in Iraqi Jews as it is in Ashkenazi Jews, with allele
frequencies of 0.0167 and 0.0217, respectively. The type III
mutation was not detected in any of the Iraqi Jews examined,
whereas in Ashkenazi Jews its allele frequency was 0.0254.5
Iraqi Jews constitute the largest subgroup of contemporary
Middle Eastern Jews. They are thought to represent the original Middle Eastern Jewish gene pool because they had lived
in relative isolation from the times of the Babylonian exile
in 586 BC until their immigration to Israel in 1950 to 1951.
Ashkenazi Jews are also thought to have stemmed from the
original pool, particularly after the destruction of the Second
Temple in 70 AD. They have consolidated into a distinct
ethnic entity in Europe in the ninth century AD.16 Sephardic
Jews constitute the third large segment of the original Middle
Eastern pool. They have migrated over the centuries along
North Africa into Sepharad (Spain in Hebrew), and following
their expulsion from Spain in 1492 have migrated back to
North Africa, Italy, the Balkan countries, and Turkey.
Given the historical information and our finding of a similar prevalence of the type II FXI mutation in Ashkenazi
and Iraqi Jews, we speculated that this mutation might have
originated in an ancient Jewish founder.5 We also hypothesized that the type III mutation stemmed from a founder who
lived at a time when the Ashkenazi Jews had already become
OAGULATION FACTOR XI (FXI) deficiency is an
autosomal recessive injury-related bleeding disorder
first described as a ‘‘new’’ form of hemophilia.1 The disorder
is highly prevalent among Jews mainly of Ashkenazi (European) origin and occurs only sporadically in other populations.2-8
The FXI (F11) gene is located on chromosome 4 (4q35).9
It is 23 kb long and is organized in 15 exons and 14 introns.10
Three mutations were initially identified in six Ashkenazi
Jewish patients and were designated type I, type II, and type
III.11 Type I mutation is a G to A substitution at the donor
splice site in the last intron (intron N) of the FXI gene; type
II is a nonsense mutation creating a premature stop codon
(Glu117Stop) in exon 5, and type III is a Phe283Leu missense mutation in exon 9 coding for a protein that fails to
be properly secreted from cells.12 Homozygotes for type III
mutation have a significantly higher level of FXI clotting
activity (6% to 14% of normal) than homozygotes for type
II mutation (0.5% to 1.5% of normal), as well as significantly
From the Institute of Thrombosis and Hemostasis, Department of
Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel;
the Chemistry Laboratory, Sourasky Tel-Aviv Medical Center, TelAviv, Israel; the Rosh-Haayin Outpatient Clinic, Rosh-Haayin, Israel; the Department of Medicine, Hasharon Medical Center, PetahTiqua, Israel; and the Thrombosis and Hemostasis Unit, Rambam
Medical Center, Haifa, Israel.
Submitted March 5, 1997; accepted June 3, 1997.
Supported in part by grant No. 2601 of the Chief Scientist of the
Ministry of Health of Israel.
Address reprint requests to Uri Seligsohn, MD, Institute of Thrombosis and Hemostasis, Department of Hematology, Sheba Medical
Center, Tel-Hashomer, 52621 Israel.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
‘‘advertisement’’ in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
q 1997 by The American Society of Hematology.
0006-4971/97/9007-0031$3.00/0
Blood, Vol 90, No 7 (October 1), 1997: pp 2654-2659
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FOUNDER EFFECTS FOR FACTOR XI MUTATIONS
2655
a distinct ethnic community. In the present study we addressed these questions directly by analyzing FXI gene polymorphisms in deficient patients and control individuals of
Iraqi and Ashkenazi Jewish as well as of Arab origin. We
also surveyed other Middle Eastern Jews, Sephardic Jews,
and Arabs for the type II and type III mutations.
MATERIALS AND METHODS
Subjects with FXI deficiency and their family members. Probands affected by FXI deficiency were previously diagnosed following referral for an injury-related bleeding episode or for a work-up
of an occasional finding of prolonged activated partial thromboplastin time. Other FXI-deficient subjects or unaffected individuals were
identified during examination of family members of probands. Diagnosis of FXI deficiency was based on finding of a diminished plasma
factor XI activity, which in homozygotes or compound heterozygotes
for the various mutations was less than 15 U/dL, and in heterozygotes
from 22 to 60 U/dL.17 Genotype definition was established by analysis of type I through type IV mutations as described elsewhere.5,14
Eighty-three probands (from 80 families) were of Ashkenazi Jewish origin, 7 probands were of Iraqi Jewish origin (7 families), 6
probands were of Arab origin (from 4 Moslem and 2 Christian
families), and one proband was of Yemenite Jewish origin.
Control subjects of Sephardic/North African and Middle Eastern
Jewish and of Arab origins. Patients admitted to the Departments
of Medicine or Surgery of the Sheba, Hasharon, Rambam, Assaf
Harofeh, Rabin, and Sourasky Tel-Aviv Medical Centers or to RoshHaayin community clinic were examined for the common type II
and type III mutations causing FXI deficiency in Jews. The study
was approved by the human subject ethics committee. Definition of
ethnic origin was based on the country of birth of the individual’s
four grandparents. The following groups of subjects were categorized: Sephardic/North African Jews, consisting of subjects of Moroccan, Algerian, Tunisian, Lybian, Turkish, and Greek origins; Middle Eastern Jews, comprising subjects of Iranian, Yemenite, and
Syrian origin; and Arabs. Iraqi and Ashkenazi Jews were previously
sampled and classified as separate groups.5
Analysis of four polymorphic markers in the FXI gene. DNA
was prepared from fresh or frozen blood by the desalting procedure.18
A previously described restriction fragment length polymorphism
(RFLP) in intron E and a dinucleotide repeat polymorphism in intron
B were analyzed by polymerase chain reaction (PCR) as reported.19,20
Two new polymorphisms were discovered during the progress of
this study. One was a single stranded conformation polymorphism
(SSCP) in intron A. For its detection the following primers were
designed: forward primer, derived from an intron A sequence
(5*-TCAGATGGTGGCCATGAGAAGG-3*); and a reverse primer,
derived from an intron B sequence (5*-TTCACCTCAATTCCTACCCTGC-3*). The 544-bp amplified fragment that was obtained
consisted of 317 bp of intron A, 56 bp of exon 2, and 171 bp of
intron B of the FXI gene. Although the exact change of sequence
responsible for this poymorphism has yet to be determined, its location is most probably in intron A. This is supported by the detection
of the SSCP in a 330-bp fragment derived from the 5* end of the
544-bp amplified fragment by Fokl digestion. The 330-bp fragment
contains 317 bp of intron A and 13 bp of exon 2 corresponding to
the Fokl restriction site.
The discovery of the second new polymorphism emanated from
the observation of 10 AT repeats in intron M of the reported FXI
gene sequence.10 PCR using a forward primer, 5*-CTGAGATTGCAGCACTGCAC-3*, and a reverse primer, 5*-GTTCGTTTGTAGAATCATAC-3*, flanking this region disclosed four distinct alleles.
PCRs for the detection of the new intron A and intron M polymorphisms were performed in a total volume of 10 mL containing 50
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ng of genomic DNA, 5 pmol of each primer, 20 mmol/L of each
dNTP, 0.1 mL 32p-dATP (2,000 Ci/mmol), and 0.25 U Taq polymerase obtained from Advanced Biotechnologies (Surrey, UK). The
amplification reaction for intron A was started by denaturation at
947C for 5 minutes and followed by 30 cycles consisting of denaturation at 957C for 30 seconds, annealing at 667C for 45 seconds and
extension at 727C for 90 seconds. For amplification of the intron M
polymorphic fragment, initial denaturation at 947C was followed by
40 cycles consisting of denaturation at 987C for 15 seconds, annealing at 507C for 20 seconds, and extension at 727C for 15 seconds.
At the end of both PCRs, 5-minute extensions at 727C were performed. The samples were then prepared for electrophoresis by adding 9 mL aliquots to 20 mL stop solution (95% formamide, 10 mmol/
L NaOH, 0.25% bromphenol blue, 0.25% xylene cyanol), heating
at 947C for 5 minutes, and snap-chilling in ice water. In the SSCP
assay of intron A, the PCR product was resolved by electrophoresis
in 5% mutation detection enhancement (MDE) gel (AT Biochemical,
Malvern, PA) at 6W constant power for 14 to 16 hours at room
temperature. The amplification products of intron M were resolved
by electrophoresis in a 6% polyacrylamide sequencing gel operated
at 2,500 V for 3 hours. Gels were dried and visualized by autoradiography. The allele frequencies of the four polymorphic markers were
determined in independent chromosomes of individuals belonging
to the studied families whose FXI genotypes were normal and in
samples of the Iraqi Jewish and Arab subjects surveyed for the type
II mutation.
Derivation of FXI haplotypes. Haplotypes were derived as follows: (1) By analysis of the FXI gene polymorphisms in 17 unrelated
homozygotes for the type II mutation and 13 unrelated homozygotes
for the type III mutation; (2) by segregation analysis of polymorphisms in 292 members of 67 unrelated informative families in
whom FXI-deficient patients were detected; (3) by segregation analysis of the polymorphisms in members of two Iraqi Jewish and four
Arab families with patients affected by other inherited coagulopathies; and (4) by analysis of samples of Iraqi Jews and Arabs who
were found to be homozygous for at least 3 of the 4 polymorphisms.
RESULTS
Characterization of the four FXI gene polymorphisms.
Figure 1 depicts representative analyses of the four polymorphisms examined, and Table 1 summarizes the frequencies
of the respective alleles in normal Ashkenazi Jewish, Iraqi
Jewish, and Arab chromosomes. For the SSCP in intron A,
two alleles were identified. The polymorphic information
content (PIC) of this polymorphism was 0.34, 0.37, and 0.37
in Ashkenazi Jews, Iraqi Jews, and Arabs, respectively. For
the intron B CA repeat polymorphism, we observed four
alleles instead of two alleles originally reported.20 PIC values
for this polymorphism were 0.58 in Ashkenazi Jews, 0.61
in Iraqi Jews, and 0.53 in Arabs. For the two allelic intron
E RFLP, the PIC values were 0.36 in both Ashkenazi and
Iraqi Jews and 0.37 in Arabs. For the intron M polymorphism, four alleles were detected. PIC values were 0.30,
0.34, and 0.17 in Ashkenazi Jews, Iraqi Jews, and Arabs,
respectively.
Founder effects for type II and type III mutations. The
frequency distribution of haplotypes in control and mutant
chromosomes is shown in Fig 2. The 26 identifiable haplotypes in control Iraqi Jewish, Ashkenazi Jewish, and Arab
chromosomes were similarly distributed and one of them,
ie, 2-4-1-2 predominated in all three populations.
All independent chromosomes bearing the type II muta-
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2656
PERETZ ET AL
Fig 1. Analysis of four polymorphic markers in
introns A, B, E, and M of the FXI gene. SSCP in intron
A: an autoradiogram shows samples of a heterozygote for alleles 1/2 (lane 1), a homozygote for allele
2 (lane 2), and a homozygote for allele 1 (lane 3). CA
repeat in intron B: an autoradiogram shows samples
of a heterozygote 2/4 (lane 1), a homozygote for allele 3 (lane 2), a heterozygote 1/2 (lane 3), a heterozygote 2/4 (lane 4), and a homozygote for allele 2 (lane
5). RFLP in intron E: an ethidium bromide–stained
agarose gel shows in lane 1 the pBR322 DNA/Alul
marker, samples of homozygotes for allele 2 (lane 2)
and allele 1 (lane 3), and a sample of a heterozygote
for alleles 1/2 (lane 4). AT repeat in intron M: an
autoradiogram shows samples of a heterozygote for
alleles 1 and 3 (lane 1), a homozygote for allele 3
(lane 2), a heterozygote for alleles 2 and 4 (lane 3),
a homozygote for allele 3 (lane 4), a heterozygote
for alleles 3 and 4 (lane 5), and a heterozygote for
alleles 1 and 3 (lane 6).
tion, which were of Ashkenazi Jewish (n Å 80), Iraqi Jewish
(n Å 10), and Arab (n Å 11) origins, were characterized by
a single haplotype, ie, 1-2-2-2. The same haplotype was
associated with the type II mutation in a Yemenite Jewish
family (Fig 3).
The haplotype analysis in type II heterozygotes detected
during the population surveys yielded the findings that two
heterozygotes of Syrian and Moroccan Jewish origins were
homozygotes for the 1-2-2-2 haplotype. In 21 additional het-
Table 1. Allele Frequencies of FXI Gene Polymorphisms in
Ashkenazi and Iraqi Jews and in Arabs
Polymorphism*
Intron
Allele
A
1
2
B
1
2
3
4
E
1
2
M
1
2
3
4
Frequency†
Ashkenazi Jews
0.32
0.68
(n Å
0.02
0.37
0.23
0.38
(n Å
0.39
0.61
(n Å
0
0.16
0.80
0.04
(n Å
128)
134)
137)
131)
Iraqi Jews
0.47
0.53
(n Å
0
0.42
0.23
0.35
(n Å
0.39
0.61
(n Å
0
0.13
0.67
0.20
(n Å
Arabs
0.41
0.59
(n Å
0
0.38
0.16
0.47
(n Å
0.45
0.55
(n Å
0.01
0.18
0.68
0.13
(n Å
104)
102)
132)
141)
* See Fig 1.
† N indicates the number of chromosomes examined.
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91)
116)
126)
erozygotes (14 of Iraqi, 1 of Yemenite, 1 of Moroccan, and
1 of Turkish Jewish origins and 4 of Arab origin) the polymorphic profile was also consistent with the association of
the type II mutation with haplotype 1-2-2-2. The 1-2-2-2
haplotype was relatively rare in control Ashkenazi Jewish
(10.9%), Iraqi Jewish (12.2%), and Arab (8.2%) chromosomes (Fig 2).
Sixty independent chromosomes bearing the type III mutation, all of Ashkenazi Jewish origin, were also characterized
by a single yet another haplotype, ie, 2-3-2-2 (Fig 2). Interestingly, this haplotype was more frequent in normal Ashkenazi Jewish chromosomes (14.5%) than in normal Iraqi
Jewish chromosomes (4.1%) and normal Arab chromosomes
(6.1%).
Frequency of type II and type III mutations in Arabs
and Sephardic/North African and Middle Eastern Jews.
Among 841 Jewish subjects of Sephardic/North African or
Middle Eastern origin and 313 Arab subjects, none was
found to bear the type III mutation (Table 2). These data are
similar to a previous survey of Iraqi Jews and contrast the
relatively high frequency (0.0254) of the type III mutation
in Ashkenazi Jews.5
Five type II heterozygotes were identified among 947 Sephardic/North African and Middle Eastern Jews. These five
individuals were of Moroccan (two), Turkish, Yemenite, and
Syrian origins. Thus, the type II mutation was 6 to 8 times
less frequent in Sephardic/North African and Middle Eastern
Jews than in Iraqi or Ashkenazi Jews (Table 2). Among 382
Arab subjects, five heterozygotes were detected yielding a
type II allele frequency of 0.0065.
DISCUSSION
103)
The presented data indicate that the type III mutation that
causes FXI deficiency in Jews is confined to those of Ash-
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FOUNDER EFFECTS FOR FACTOR XI MUTATIONS
2657
Fig 2. Frequency distribution of FXI gene haplotypes observed in Ashkenazi Jews, Iraqi Jews, and
Arabs. The numbers on the abcissa denote from bottom to top the allele numbers of polymorphisms in
introns A, B, E, and M (as detailed in the legend of
Fig 1). For instance, the haplotype designated 1211
is composed of allele 1 of intron A polymorphism,
allele 2 of intron B polymorphism, allele 1 of intron
E polymorphism, and allele 1 of intron M polymorphism. The lower and upper panels represent normal
chromosomes and chromosomes bearing type II or
type III mutations, respectively. Note that all chromosomes carrying the type II mutation are characterized by the same 1-2-2-2 haplotype that is observed
in 8% to 12% of normal chromosomes. The chromosomes bearing the type III mutation are confined to
Ashkenazi Jews, all characterized by haplotype 2-32-2.
Fig 3. Pedigree of a Yemenite Jewish family depicting a proband
with severe FXI deficiency (less than 1 U/dL) caused by homozygous
type II mutation and six family members who are heterozygotes. It
can be seen that the 1-2-2-2 haplotype segregates with the type II
mutation as in Iraqi and Ashkenazi Jewish and Arab chromosomes
bearing this mutation (Fig 2).
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kenazi origin. None of the 2,686 alleles examined of North
African/Sephardic and Middle Eastern Jews was found to
bear this mutation, nor was it observed in 626 alleles of
Israeli Arabs (Table 2). We previously showed that the allele
frequency of the type III mutation in Ashkenazi Jews is
0.0254.5 In this study we showed a founder effect for this
mutation, with all 60 mutant alleles examined having the
same 2-3-2-2 haplotype (Fig 2). This haplotype was observed
in only 14.5% of normal Ashkenazi Jewish chromosomes.
Taken together our findings strongly suggest that the type
III mutation occurred in an Ashkenazi Jewish individual who
lived at a time after the divergence of Ashkenazi Jews from
their original Middle Eastern ancestors (Fig 4).
Unlike the type III mutation, the type II mutation is not
confined to Ashkenazi Jews. In a previous study we showed
that the allele frequency of the type II mutation was quite
similar in Ashkenazi (0.0217) and Iraqi Jews (0.0167), the
latter representing the original gene pool of Jews who have
remained in the Middle East for 2,500 years.5 In this study
we extended our observations to other Jewish ethnic groups
and Arab individuals. Among 1,894 alleles of North African,
Sephardic, and Middle Eastern Jewish origins (excluding Iraqi
Jews), we detected only five that carried the type II mutation.
This 6- to 8-times-lower allele frequency, when compared
with the frequency in Iraqi and Ashkenazi Jews (Table 2), is
reflected by our observation during the last 30 years of only
one family of Yemenite Jewish origin with a severely affected
patient who was homozygous for the type II mutation (Fig
3). Among Arabs we have encountered over the years, six
unrelated families in whom patients with severe type II FXI
deficiency manifested excessive bleeding. Conceivably, this
is related to the somewhat higher prevalence of the mutant
allele (0.0065) in the general Arab population when compared
with the 0.0026 allele frequency in North African/Sephardic
or non-Iraqi Middle Eastern Jews (Table 2).
Of great interest was the finding that all 103 informative
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2658
PERETZ ET AL
Table 2. Frequency of FXI Type II and Type III Mutations in Israeli Ethnic Groups
Type II Mutation
Ethnic Group
Ashkenazi Jews*
Iraqi Jews*
Other Middle
Eastern Jews
Sephardic/North
African Jews
Arabs
Type III Mutation
N
Heterozygotes
Homozygotes
Allele
Frequency
N
Heterozygotes
Homozygotes
Allele
Frequency
531
509
21
17
1
0
0.0217
0.0167
531
502
25
0
1
0
0.0254
—
387
2
0
0.0026
387
0
0
—
560
382
3
5
0
0
0.0027
0.0065
454
313
0
0
0
0
—
—
* Previously reported.5
independent chromosomes bearing the type II mutation of
Ashkenazi, Iraqi, Yemenite, Syrian, and Moroccan Jews
and of Arabs were characterized by one haplotype. This
1-2-2-2 haplotype (Fig 2) was observed in only 8% to
12% of normal chromosomes in Ashkenazi Jews, Iraqi
Jews, and Arabs and hence the data are consistent with a
founder effect.
The various Jewish individuals affected by the type II
mutation belong to communities that diverged mainly during
the 600 years that elapsed between the destruction of the
First Temple in 586 BC and the destruction of the Second
Temple in 70 AD (Fig 4). Consequently, it is likely that the
type II mutation arose in an individual who lived in those
ancient times or before. Gene flow might have been responsible for the transfer of the type II mutation to the Arabs who
spread in the Middle East and occupied the land of Israel as
of the Seventh century AD and later.
During the last decades a significant number of rare autosomal recessive disorders have been described among Jews
of various origins.21 Most disorders are confined to one of
the major segments of the Jews, namely Ashkenazi, Sephardic, or Middle Eastern, with none of the disorders being
common to Ashkenazi and non-Ashkenazi Jews. Type II
FXI deficiency is therefore the first disorder that is common
to Ashkenazi and non-Ashkenazi Jews. The mechanisms in-
volved in the emergence of the relatively high prevalence of
the hereditary disorders in Ashkenazi and non-Ashkenazi
Jews is still debated.22 Protagonists of the hypothesis of a
selective advantage of heterozygotes base their arguments
mainly on the phenomenal prevalence of four rare lysosomal
disorders in Ashkenazi Jews and on the identification of multiple mutations causing them. However, in none of these disorders nor in patients with FXI deficiency of either type has an
advantage been shown. Protagonists of the founder effect and
drift hypothesis base their arguments on similar clustering of
genetic disorders in the Amish, Finns, and French-Canadians;
on the contractions and excessive expansions particularly of
Ashkenazi Jews from the year 1500 and onwards; and on the
absence of the specific mutations in populations that lived in
proximity with Ashkenazi Jews.22,23 Recently, by determining
the degree of linkage disequilibrium and the recombination
frequency between the locus of idiopathic torsion dystonia and
adjacent microsatellite markers, the time when the mutation
causing this disease in Ashkenazi Jews took place was estimated to be around the year 1650.23 Work on dating the origin
of other Ashkenazi Jewish disorders is in progress. At present
there are only few characterized polymorphisms neighboring
the FXI gene. When such markers become available it will
be possible to estimate more precisely the time when the type
II and type III mutations arose.
Fig 4. A simplified scheme showing the common
origin of the three major segments of contemporary
Jews and explaining the current distribution of the
type II and type III mutations. The predicted time
when type II and type III mutations occurred in the
FXI gene are indicated by horizontal arrows. We
speculate that gene flow has been responsible for
the transfer of type II mutation from Middle Eastern
Jews to Palestinian Arabs after the settlement of
Arabs in Israel in the Seventh century AD.
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FOUNDER EFFECTS FOR FACTOR XI MUTATIONS
2659
ACKNOWLEDGMENT
The authors are indebted to Professor Avinoam Adam of the TelAviv University for useful discussion, to Rusa Eichel, Ety Zwang,
and Rivki Yatuv for skillful technical assistance, and to Alice Nahum
and Ruth Apel for excellent secretarial work.
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blda
WBS: Blood
From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
1997 90: 2654-2659
The Two Common Mutations Causing Factor XI Deficiency in Jews Stem
From Distinct Founders: One of Ancient Middle Eastern Origin and Another
of More Recent European Origin
Hava Peretz, Avital Mulai, Sali Usher, Ariella Zivelin, Avihai Segal, Zahavi Weisman, Moshe Mittelman,
Hannah Lupo, Naomi Lanir, Benjamin Brenner, Ofer Shpilberg and Uri Seligsohn
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