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Immunoglobulin (Gm) allotypes in a sample of Canadian Ashkenazic jews.

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Immunoglobulin (Gm) Allotypes in a Sample of
Canadian Ashkenazic Jews
L. LEIGH FIELD,' J. ALEXANDER LOWDEN ' AND AJIT K. RAY
'
Department ofdnthropology, UriiLNersityof Toronto. Toronto, Ontario, Canada,
M5S 1AI and Research Institute, The Hospital f o r s i c k Children,
Toronto, Ontario, Canada, M5G 1x8
i
K EY WORDS Gm
variation
.
Haplotypes
a
Ashkenazi
Jews
-
Genetic
ABSTRACT
Gm typing on t h e serum specimens of 507 Ashkenazic Jews (predominantly of Polish-Russian ancestry! from Toronto, Canada has established
andGm 1,17;5, and the absence of
the presence of h a p l o t y p e ~ G m ~Gm
: ~ ,'z21, Gm
haplotypes Gm1:13J5.16,
and Gm1;5.6,24which have been found in other
Jewish peoples. It is suggested t h a t Ashkenazic populations have lower frequencies of haplotype Gm 1 ~ 1 7 : 5than non-European Jewish populations, and t h a t some
eastern European Jewish populations have acquired the Gm 1;13,15,16 h a PlotYPe
through gene flow from Central Asia. Thus Jewish populations show differences
in the Gm system; many of t h e differences may be in the direction of similarities
to neighbouring non-Jewish populations.
It would be interesting to know t h e degree
of genetic differentiation among modern Jewish populations, and t h e degree of similarity of
each population to local non-Jewish peoples
inhabiting t h e same geographic region. Such
information, accumulated for many genetic
markers, would provide the beginnings for a
study of drift, selection and gene flow within
and across a cultural boundary. The Gm genetic system is particularly appropriate for
describing interpopulational differences, since
the kind as well as the frequency of Gm haplotypes often varies from population to population (for review, see Johnson e t al., "77;
Schanfield and Fudenberg, '75). Table 1 presents the Gm haplotypes which commonly occur in populations relevant to this paper; i t
also gives the abbreviated haplotype notation
t h a t will be used throughout the paper. Steinberg ('73) reported t h e presence 0fGrn','~3~
and
Gm1,13J5J6 in a sample of American Ashkenazic Jews. I t was suggested t h a t these
haplotypes indicate admixture with Black
Africans and San (Bushmen), respectively.
The results of Gm typing in another sample of
Ashkenazic Jews a r e reported here, followed
by a discussion of how the data relates to the
more extensive problem mentioned above.
AM. J. PHYS. ANTHROP. (1978)48: 159-164.
MATERIALS AND METHODS
Over 6,000 serum specimens of self-identified Ashkenazic Jews were available from a
Tay-Sachs carrier screening programme conducted in Toronto, Canada by J. A. Lowden.
The 507 individuals randomly selected for Gm
testing were primarily of the same generation
and included only two pairs of known relatives. Table 2 shows the origins of the parents
of t h e test individuals. Eighty percent of the
parents originated from Poland and Russia,
and many of the remainder came from other
eastern European countries. About one-half
(263/497 = 53%)of the test individuals were
of homogeneous parentage - t h a t is, both
parents originated from the same country.
Eighty-seven percent (2291263) of these had
parents from Poland or Russia; only 341263
(13%)had parents from some other country.
Of the 234 individuals of heterogeneous parentage, 2171234 (93%)had one parent from
Poland and/or Russia, while 17/234 (7%)had
neither parent from Poland or Russia. Homogeneous parentage occurred in 64% of those
born before 1940, but in only 46%of those born
during or after 1940 (x' = 12.89, df = 1, P <
0.001).
159
160
L. LEIGH FIELD, J. ALEXANDER LOWDEN, AND AJIT K. RAY
TABLE 1
Gm haplotypes common in certain population groups
Gm haplotype
Extended notation
Abbreviated notation
Gm3,5.10,11,13,14,26,27
Gm 1,17.21.26,27
Gm 1,2.17;21,26.27
Gm 1,17,5,10,11,19,14,26,27
Gm 1,17,6,6,10.11,14.26.27
Gm 1,17.5.6.11,24,26
Gm1,17;10,11,13.15,16,27
~~1,3,5.10.11.13.14.26,27
TABLE 2
Country
of
origin
of
CoUntTv
No Darents
Poland
Russia '
Austria
Roumania
Hungary
Germany
Czechoslovakia
England
North Africa
Other Europe
442
355
45
43
35
20
15
13
10
16
994
parents
%,
of total
44.5
35.7
4.6
4.3
3.5
2.0
1.5
1.3
1.0
1.6
100.0
I The high percentage of Polish ancestors IS characteristic of the
Toronto Jewish population and 1s not seen in other Canadian cities,
where the percentage Poliah varies from 24-26 and the percentage
Russian varies from 40-57 (Lowden, '75).
The exact composition wa3: 312 "Russia," 2 "White Russia," 29
"Lithuania," 3 "Latvia," 9 "Ukraine."
497:507 responded to the question abuut origins.
TABLE 3
Reagents usrd for testing Grn and A m antigens
Antigen
Numeric Alphameric
Gl m
G3m
A2m
1
a
2
X
3
f
17
z
5
6
13
b'
14
15
16
21
b'
C 1
b3
S
t
g
1
1
2
2
Population p r o w
Caucasian
Caucasian, Oriental,
Bushmen
Caucasian, Oriental
Negro, Bushmen
Negro
Negro
Oriental, Bushmen
Oriental
Ayylutlnator
Mor
Mor
TY 1
How
Haw
R-15
Anti-D coat
Bra
Bar
Bar
Dul
Ell
Bar
Pay
Cur
Ing
Ska
Goe
Gai
Ros
Cli
Cam
Kre
Far
Tay
Her
For
Dur
Dur
Dur
Puh
Puh
Bar
L The nomenclature is based on recommendations of a W.H.O.
meeting held in J u l y 1974 (W.H.O. Committee on Human Immunoglobulin
Allotypes, '761.
The serum specimens were tested, using the
standard agglutination-inhibition technique
described by Steinberg ('621, for Glm(1,2,3)
and G3m(5,6,13,14,21), with the reagents
listed in table 3. Selected samples, indicated in table 4, were also tested for Glm(171,
G3m(15,16), and A2m(1,2) to search for certain rare haplotypes. Appropriate controls
were employed at all times. Twenty-five of the
unknown sera exhibited agglutinating activity; these were heat inactivated a t 63°C and
re-typed.
Haplotype frequencies were estimated by
the maximum likelihood programme MAXIM
(Kurczynski and Steinberg, '67).
RESULTS
The Gm phenotypes of the 507 individuals
are given in table 4. In the absence of family
data, decisions about the probable genotypes
of the observed phenotypes must be based on
knowledge of the commonly occurring haplotypes in relevant populations. The first five
phenotypes listed provide evidence for the
presence of the haplotypes Gm3i5,Gm
and
Gm1~2;21,
which are common in Europe. The
last two phenotypes, Gm(1;5,13,14,21) and
Gm(1,2;5,13,14,21), suggest the presence of
the haplotype Gm1.17i5,common in Africa but
rare in Europe. Phenotype Gm(1,3;5,13,14)
without further testing could be explained by
many genotypes, the most probable being heterozygous combination of Gm3i5with Gm l-17i5,
Gm1;13915316,or Gm1.3;5. The latter two haplotypes are common in Asia. Testing for
Glm(17) and G3m(15,16) helps to distinguish
between these possibilities, since genotype
Gm3.5/Gm1,'7;5would be (17, - 15, - 1 6 ) ,
Gm3;5/Gm1:13J5J6would be (17,15,16), and
Gm3;51Gm1~3;5
would be ( - 17,- 15,-16).
When the 12 samples with phenotype Gm
(1,3;5,13,14) were tested for Glm(17) and
161
GM ALLOTYPES IN CANADIAN ASHKENAZIC JEWS
TABLE 4
Gm phenotypes of the total sample and the subgroups
Phenotype
Total sample
'
3;5,13,14
1,3;5,13,14,21
1,2,3;5,13,14,21
1;21
1,2;21
1,3,17;5,13,14
1;5,13,14,21
1,2;5,13,14,21
No.
Y,
291
134
41
20
7
12
57.4
26.4
8.1
3.9
1.4
2.4
0.2
0.2
100.0
1
1
507
Polish subgroup
No.
79
33
11
5
%
2
59.4
24.8
8.3
3.8
1.5
3
0
0
133
2.2
0.0
0.0
100.0
Russian subgroup
xo.
52
29
8
3
1
2
0
1
96
54.2
30.2
8.3
3.1
1.0
2.1
0.0
1.0
100.0
' All samples were tested for Glm(1.2,31 and G3rni5,6,13,14,21i.
'These samples were also tested for Glm(17i and C3m(15,161. In addition, they were tested for A2m(1,2)
TABLE 5
Estimated haplotype frequenczes
of
Total sample
Haplotype
Gm3,5
Gm1:PI
Gm1.23
Gm1,17;5
the total sample and the subgroups
Polish subgroup
Russian subgroup
Frequency
* S.E.
Frequency
t S.E.
Fresuencv
0.758
0.179
0.049
0.014
0.013
0.012
0.007
0.004
0.771
0.168
0.050
0.011
0.026
0.023
0.013
0.006
0.745
0.187
0.053
0.015
1
S.E.
0.031
0.028
0.016
0.009
The fit to Hardy~Weinbergexpectations using these estmated frequencies is satlsfactorg for each of the three samplesTotal sample: x' = 2.91. df = 3. 0.5 > P > 0.3.
Polish subgroup: x1 = 0.58, df :1. 0.5 > P 1 0 3.
Russian subgroup: x' - 0.54, df = 1. 0 5 > P > 0.3.
G3m(15,16), they were all (17,-15, -161,
thus providing corroborative evidence for the
presence of Gm l.17i5. Finally, phenotypes
Gm (1,3;5,13,14,2 1) and Gm (1,2,3;5,13,14,21)
could possess t h e haplotype Gm1*3;5,
but in this
case no differentiating tests are available:
Glm(17) would always be positive in these
phenotypes because it is carried by the Gm';21
andGm',2;21haplotypes. Thus, in the 507 individuals tested, there was evidence only for
t h e haplotypes Gm33, Gm
Gm1,2;21,and
Gm'.'7;5. The estimated frequencies of these
haplotypes are presented in table 5.
The 12 individuals with t h e phenotype Gm
(1,3,17;5,13,14), probable genotype Gm 3:5/
Gmi.17;5,were also tested for A2m(1,2). The
A2m markers, only recently discovered, a r e
closely linked to Gm markers. A2m(2) is rare
in "European" haplotypes; in Africa, Gm
Am2 is much more common than Gm1J7;5Am1
(Schanfield and Fudenberg, '75). Only 2/12
(17%) of the individuals tested were A2m(2)
positive, indicating t h a t Gm 1~17;5 Am' predominates in our population.
DISCUSSION
In order to search for differences in Gm fre-
quencies between Jewish populations, two
large subgroups were isolated from the Toronto sample: (1) people with Polish ancestry
only (2) people with Russian ancestry only.
Table 4 shows t h e phenotype distributions of
these two groups, and table 5 gives the estimated haplotype frequencies. The difference
between the phenotype distributions is not
significant (xz = 0.87, df = 3, 0.9 > P > 0.8).
I t is not surprising t h a t Jewish people with
Polish origins and Russian origins have similar Gm frequencies: many of their ancestors
probably came from the region surrounding
what is now the Polish-Russian border, the
northern part of a n area called the Pale of Settlement in the Nineteenth Century when i t
was contained within the Russian Empire
(Fraikor, '77). In other words, these ancestors
came from a relatively restricted geographical
area, which is not reflected in t h e political
terms chosen by their descendents t o describe
ancestral origins.
The one other detailed study of Gm variation in Ashkenazic Jews is t h a t of Steinberg
('731, who typed 248 American Jews for the
same array of Gm factors tested in the present
analysis. The population was not identified as
162
L. LEIGH FIELD, J. ALEXANDER LOWDEN, A N D AJIT K. RAY
TABLE 6
Cumparison of the phenotype distributions of Polish Jewish and non-Jewish samples
Phenotype
1
IT
111
Polish Jewish
(this study)
Polish non-Jewish
(Podliachouk e t a1 , '63)
Polish non-Jewish
(Schlesinger e t al., ' i l l
No.
3;5
1.3;5
1,2,3;5
1
1.2
%>
79
36
I1
59.4
27.0
8.3
5
3.8
2
133
1.5
100.0
No.
%,
No.
x.
193
77
24
6
5
305
63.3
182
66
30
14
8
300
60.7
22.0
10.0
4.7
2.7
100.0
25.2
7.9
2.0
1.6
100.0
Tests of significance I YS. 11. ,y' = I 56, df = 4, 0.9 > P > 0.8.
I VB. 111: x' = 2.03. df - 4, 0.8 > I' > 0.7.
' Glm!3l or G3m161 or both were detected, depending on the reagents used in the study
to origin, but was (we may presume) predomi- population comparisons should be considered
nantly from eastern Europe. Chi-square test- tentative. However, several of the non-Euroing on the phenotype distributions showed no pean groups (e.g., populations No. 37 and No.
significant difference between the American 43 from Morocco and Iran in Ropartz e t al.,
and the Toronto samples (x' = 6.71, df = 5, '65; Kurdish Jews from northern Iraq in
0.3 > P > 0.2).3 It may be more appropriate to Steinberg et al., '70; Yemenite Jews and Kurperform a x 2 test using the estimated hap- dish Jews from Iran in Godber e t al., '73) aplotype frequencies (Elandt-Johnson, '71); this pear to possess higher frequencies of "Grn135"
is done by generating a set of expected pheno- haplotypes than Ashkenazic Jews. An exceptypic proportions from the pooled haplotype tion is the Karaite isolate from Iraq, which
frequencies, and then comparing observed dis- Goldschmidt et al. ('76) showed to have only
But evidence from blood
tributions to those predicted from the ex- Grn395 and Grn1%21.
pected proportions. Again, the x 2 results were group and isoenzyme systems suggests that
not significant ( x 2 = 7.66, df = 7, 0.5 > P > this community has experienced considerable
0.3). The only interesting difference between genetic drift due to small population size. Furthese two Ashkenazic populations was the ther studies are needed to determine the geopresence in the American group of the hap- graphic variation of Grn1.17.5frequency in nonlotype Grn';'33'5~16(carried by 1.6%of the peo- European and European Jews. In the present
ple tested; estimated frequency = 0.008) and study, the parental origins of the 14 individits absence in the Toronto group. The hap- uals carrying Grn 1 ~ 1 7 , 5were distributed in the
lotype seems to exist in the Polish-Jewish same manner as the origins of the entire
gene pool, since it has been recorded in a Toronto group.
Podliachouk and Eyquem ('63) tested 305
Polish Jewish family (mentioned in Steinberg
et al., '70). However, it may have a frequency Poles for Glm(1,2) and G3m(5); Schlesinger
lower than 0.008 in Poland and adjoining and Luczkiewicz-Mulczykowa ('71) tested 300
Russia, and a higher frequency in some area of Poles for G l m (1,2,3). Since it is unlikely that
eastern Europe t h a t is better represented in either sample contained significant numbers
the American sample. Amongst non-Jews in of Jews, they may be considered non-Jewish
eastern Europe, Czechoslovakians have a for purposes of comparison. It is not possible to
G m 1 ; 1 3 J 5 . 1 6 frequency of about 0.004 (Schandetermine the presence or absence of the
field e t al., '75b), while further south, Hun- Gm1J7;5haplotype from their testing, but in
garians have a frequency of about 0.014 terms of the phenotypes observed, there are no
(Schanfield et al., '75a). Two samples of significant differences between the Polish disRoumanians (quoted in Johnson et al., '77) tributions and the Toronto Polish-Jewish disshow frequencies of 0.003 (north Roumania)
The rare haplotypes Gm L17;5 and Gm 1;13,15,16were considered
and 0.013 (Bucharest).
as one for purposes of xi testing, sinceGm1;13,15.16 did not exist in
Although some Gm data has been published the Toronto sample.
"Gm1;5" may include Grn1;5,6 and Gm1;5,6,24 as well as
on non-European Jews, it is less extensive, in
All three haplotypes were detected by Steinberg et al. ('701
sample size or in number of factors tested, Gm1.17;5
in Iraqi Kurdish Jews, but the other studies of non-EuropeanJews did
than the Ashkenazic material and therefore not test for G3m (6,241, which would have permitted differentiation.
GM ALLOTYPES IN CANADIAN ASHKENAZIC JEWS
tribution (table 6 ) . More detailed studies of
Gm variation in Poland, and in Russia, have
not yet been conducted.
I t is suggested t h a t Gm differences exist between geographically separated Jewish populations and t h a t Jews may resemble their nonJewish neighbours. However, this does not
imply how the differences and similarities
have arisen. Admixture may be postulated,
but i t should be supported by the history
of population movements and contacts. For
example, we consider i t more probable t h a t
the haplotype Gm1:13.153detected by Steinberg ('73) in Ashkenazic Jews is the result of
gene flow from peoples of Central Asia who
invaded Europe around 500-1500 A.D., rather
t h a n gene flow from S a n (Bushmen) of southern Africa (in the past, people related to the
San inhabited eastern Africa). Evidence from
non-Jewish Hungarians (Schanfield e t al.,
'75a) suggests t h a t these westward moving
Asians had higher frequencies of Gm 1 ; 1 3 ~ 1 5 ~ 1 6
t h a n Gm1x3i5;this may explain the failure to
find the latter haplotype in Jewish populations t h a t possess t h e former.
The Gm 'J~;'
haplotype exists in non-polymorphic frequencies (-- 0.003) in several
western a n d e a s t e r n European countries
(Schanfield et al., '75b). Non-European Jewish
populations appear to have higher frequencies
- for example, 0.033 in Kurdish Jews from
northern Iraq (Steinberg e t al., '70). Middle
Easterners generally may have higher frequencies - for example, 0.037 in Lebanese
(Lefranc e t al., '76). Thus the frequencies observed in Ashkenazic Jews - 0.014 (this
study) and 0.010 (Steinberg, '73) - a r e intermediate. Again, i t is possible to postulate
admixture. The haplotype was first acquired
by J e w s through gene flow from Black
Africans, then during the Diaspora, i t was
reduced in frequency by cryptic gene flow
from Europeans. However, perhaps admixture
is being given too prominent a role in explaining differences and similarities in Gm
frequencies. The presence of Gm1J7,5in Jews
does not require a n African origin, since this
haplotype could arise through recombination
between Gm3;5and Gm1iZ1(Schanfield et al.,
'75a). The results of A2m typing in this study
may be interpreted as supporting a nonAfrican origin: t h e Gm1J7:5Am' haplotype
predominates in t h e Jewish sample whereas
Gm1J7;5Am2is the more common haplotype in
Africa. Furthermore, any decrease in t h e frequency of Gm1J7;5during t h e time Jews have
163
inhabited Europe could be the result of evolutionary convergence. The frequencies of genetic variants in the structure of immunoglobulin molecules may be strongly affected
by environmental factors, even if the operation of selection is not at present demonstrable.
ACKNOWLEDGMENTS
We would like to thank Doctor A. G. Steinberg for generously providing many of the
anti-sera used, training in Gm typing, and
access to the MAXIM programme. Thanks
also go to Doctor H. Gershowitz for donation of
anti-D for Glm(3) and to Doctor M. S. Schanfield for kindly typing G3m(15,16) and A2m
(1,2).We have benefited from the comments of
Doctors H. Gershowitz, T. E. Reed, M. S.
Schanfield, A. G. Steinberg, and E. J. E.
Szathmary. This research was supported in
part by a n Ontario Graduate Scholarship and
by Postgraduate Scholarship 1560 from the
National Research Council of Canada. The
Office of Research Administration, University of Toronto, also gave financial assistance.
LITERATURE CITED
Elandt-Johnson, R. 1971 Probability Models and Statistical Methods in Genetics. Wiley & Son, New York.
Fraikor, A. L. 1977 An anthropological analysis of TaySachs disease: genetic drift among the Ashkenazic Jews.
SOC.Biol., 24: 117.134.
Godber, M. J., A. C. Kopec, A. E. Mourant, D. Tills and E. E.
Lehmann 1973 The hereditary blood factors of the
Yemenite and Kurdish Jews. Phil. Trans. R. Soc. Lond. B,
266: 169-184.
Goldschmidt, E., K. Fried, A. G. Steinberg and T. Cohen
1976 The Karaite community of Iraq in Israel: a genetic
study. Am. J. Human Genet., 28: 243.252.
Johnson, W. E., P. H. Kohn and A. G. Steinberg 1977 Population genetics of the human allotypes Gm, Inv, and A2m,
a n analytical review. Clinical Immunol. and Immunopath., 7: 97-113.
Kurczynski, T. W., and A. G. Steinberg 1967 A general
program for maximum likelihood estimation of gene frequencies. Am. J. Human Genet., 19: 178-179.
Lefranc, G., L. Rivat, C. Rivat, J. Loiselet and C. Ropartz
1976 Evidence for "deleted' or "silent" gene homozygous
a t the locus coding for the constant regionof the y 3 chain.
Am. J. Human Genet., 28: 51-61.
Lowden, J. A. 1975 Tay-Sachs screening and prevention:
the Canadian experience. Paper presented a t the First Internat. Conf. on Tay-Sachs Disease, Palm Springs, California.
Podliachouk, L., and A. Eyquem 1963 Les facteurs seriques
Gm (a), Gm (b), Gm (XI, e t Gm-like dans la race blanche.
Comptes Rendus Societe de Biologie, 157: 732-736.
Ropartz, C., P:Y. Rousseau and L. Rivat 1965 Hypotheses
sur la genetique formelle du systeme Gm chez les Caucasiens. Humangenetik, 1: 483-496.
Schanfield, M. S., and H. H. Fudenberg 1975 The a n t h r o p logical usefulness of the IgA allotypic markers. In:
Biosocial Interrelationships in Population Adaptation.
Mouton, Amsterdam, pp. 105-114.
164
L. LEIGH FIELD, J. ALEXANDER LOWDEN, AND AJIT K. RAY
Schanfield, M. S., J. Gergely and H. H. Fudenberg 1975a
Immunoglobulin allotypes of European populations I. Gm
and Km (Inv) allotypic markers in Hungarians. Hum.
Hered., 25: 370-377.
Schanfield, M. S.. P. Herzog andH. H. Fudenberg 1975b Immunoglobulin allotypes of European populations 11. Gm,
Am, and Km (Inv)allotypic markers in Czechoslovakians.
Hum. Hered., 25: 382-392.
Schlesmger, D., and A. Luczkiewicz-Mulczykowa 1971 The
Gm (l),Gm (21, and Gm (4) factors in the Polish population. Archs. Immunol. Ther. Exp., 19; 703-708.
Steinberg, A. G. 1962 Progress in the study of genetically determined human gamma globulin types !the Gm and
Inv types). In: Progress in Medical Genetics. Vol. 11. A. G.
Steinberg and A. G. Bearn, eds. Grune and Stratton, New
York, pp. 1-33.
- 1973 The Gm and Inv allotypes of some Ashkenazic Jews living in northern U.S.A. Am. J. Phys.
Anthrop., 39: 409-412.
Steinberg, A. G., C. Levene, E. Goldschmidt and T. Cohen
1970 The Gm and Inv allotypes in kindreds of Kurdish
Jews. Am. J. Human Genet., 22: 652-661.
W.H.O. Committee on Human Immunoglobulin Allotypes
1976 Review of the notation for the allotypic and related
markers of human immunoglobulins. The J. Immunol.,
I 1 7: 1056-1058.
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