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Distribution of HLA antigens in Polish and German populations in Milwaukee Wisconsin.

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Distribution of HLA Antigens in Polish and German
Populations in M i lwaukee, Wisconsin
JOAN c. STEVENSON AND RENE J. DUQUESNOY I
Department of Anthropology, University of Wisconsin-Milwaukee and The Milwuukee
Blood Center, Ine., Milwaukee, Wisconsin 53201
K E Y WORDS Poles Germans . HLA . Haplotype
association . Slavonic
a
-
Gametic
ABSTRACT
Gene and haplotype frequencies for HLA-A and HLA-B antigens were determined in Milwaukee blood donors of German and Polish descent. Gene frequencies for A25 and B18 were significantly higher in Poles than
in Germans. Significant gametic associations were noted for Al-B8, A29-Bl2
and AW30-B13 in both populations. Gametic association for A3-B7 was only
found in Germans, while the A25-Bl8 haplotype frequency was significantly increased in Poles. Since the latter haplotype has also been found in Yugoslavs,
Ukrainians and Czechs, it is possible that A25-Bl8 represents a Slavonic
marker.
Histocompatibility testing or HLA typing
has been shown to be a powerful tool for anthropological analysis of human populations
(Dausset and Colombani, '72). The multiallelic HLA system is the most polymorphic
genetic system presently known. Most extensively described have been the products of
HLA-A and HLA-B genes; more than 20 antigens controlled by each of these genes have
been recognized (Kissmeyer-Nielsen,'75).
Although HLA information has been reported on some Central European groups (Albert
et al., '72; Bertrams et al., '71; Gleichman, '74;
Kastelan e t al., '74; Menzel and Richter, '72;
Lenhart et al., '77; Singal and Bhargava, '75)
no articles have been published on Poles, and
available data on Germans do not include
some of the more recently discovered HLA antigens. This paper presents results of an analysis of HLA-A and HLA-B antigens in blood
donors in Milwaukee, Wisconsin, who were of
Polish or German descent.
The majority of Poles in Milwaukee arrived
between 1880 and 1900 from what was then
Austrian and Russian territory, (Milwaukee
Writer's Project, '47). The periods of greatest
German emigration to Wisconsin were between 1846 and 1854 and from 1881 to 1884
(Faust, '27). Most Milwaukee Germans came
AM. J . PHYS. ANTHROP. (1979)50: 19-22.
from Rhenish Prussia, Bavaria, Luxenburg,
Baden and Saxony, (Gregory, '31).
METHODS
Serum samples of Milwaukee Poles and Germans were collected a t the Milwaukee Blood
Center from unrelated donors of mixed ages
and both sexes who indicated on questionnaires that all four grandparents were of direct Polish or German descent.
The standard NIH microlymphocytotoxicity
test (Terasaki's technique modified) was used
to determine the HLA type of the blood donors
in this study (Ray et al., '76). The following
HLA specificities were identified: Al, A2, A3,
A9, A10, A l l , AW23, AW24, A25, A26, A28,
A29, AW30, AW31, AW32 and AW33 a t the A
locus, and, B5, B7, B8, B12, B13, B14, B15,
BW16, B17, B18, BW21, BW22, B27, BW35,
B37 and B40 a t the B locus.
Gene frequencies were calculated by the
formula g = 1 where g is the gene
frequency and p the phenotype frequency obtained by direct counting. Statistical significance of gametic association (linkage disequilibrium) between A and B locus antigens were
' Reprint requests t o : Rene J. Duquesnoy, Ph.D.,Director, Research and Development, Milwaukee Blood Center, Inc., 1701 West
Wisconsin Avenue, P.O. Box lO-G, Milwaukee, Wisconsin 53201.
19
20
JOAN C. STEVENSON AND RENE J. DUQUESNOY
TABLE 1
Gene frequencies of HLA antigens in Milwaukee blood
donors of Polish and German descent
Milwaukee
Poles
n = 175
HLA antigens
Milwaukee
Germwns
n = 190
analyzed from 2 x 2 comparisons with the Chi
Square test using Yate's correction (CavalliSforza and Bodmer, '71).
Coefficients of association between A and B
locus antigens were calculated by the formula
r
HLA-A locus
A1
A2
A3
A9
A10
All
Awl9
AW23
AW24
A25
A26
A28
A29
AW30
AW31
AW32
AW33
Blank A
0.1514
0.2788
0.1184
0.1324
0.1088*
0.0558
0.1073
0.0172
0.1152
0.0544**
0.0544
0.0348
0.0289
0.0468
0.0086
0.0202
0.0028
0.0123
HLA-B locus
B5
B7
B8
B12 (BW44)
B13
B14
B15
BW16
B17
B18
BW21
BW22
B27
BW35
B37
B40
BW45
Blank B
0.0588
0.0992
0.0928
0.0992
0.0649
0.0202
0.0558
0.0438
0.0528
0.0583***
0.0269
0.0260
0.0680
0.1087
0.0028
0.0586
0.0000
0.0632
=
x L is the Chi Square value
&whereby
and the N is the total number of samples
tested. (Cavalli-Sforza and Bodmer, '71).
Delta values of gametic association were calculated as
0.1324
0.3233
0.1602
0.1092
0.0614*
0.0402
0.0951
0.0212
A = - d- - - b + d c + d
n
n
n
where a, b, c, d are the respective frequencies
ofthe + f , + -, - + and - - phenotypes and
b
c
d (Ceppellini, '67).
n =a
Haplotype frequencies were calculated as
the sum of the A values of gametic association
and the product of the relevant gene frequencies (Mattiuz, et al., '70).
0.0880
+ + +
0.0239**
0.0375
0.0293
0.0234
0.0320
0.0105
0.0293
0.0000
0.0488
RESULTS
Gene frequencies for HLA-A and B antigens
in Milwaukee blood donors of German and
Polish descent are shown in table 1. Blank A
and B frequencies indicate total gene frequencies of serologically undetectable products of
HLA-A and HLA-B loci, respectively. The distribution of gene frequencies for HLA antigens was similar in both population groups except for A10, A25 and B18, which were significantly higher in Poles than in Germans. The
gene frequencies for A l l , A26, AW30, B13,
BW16, BW21 and B27 were somewhat higher
and those of A3, B7, B8 and B12 were lower in
Poles than in Germans, but the differences
were not statistically significant.
In these two population groups, five gametic
associations were found in statistically significant (p < 0.01) linkage disequilibrium (table
0.0681
0.1204
0.1114
0.1477
0.0375
0.0159
0.0737
0.0320
0.0485
0.0185***
0.0185
0.0132
0.0485
0.1055
0.0028
0.0794
0.0026
0.0058
* p < 0.05.
** p < 0.01.
*** p < 0.001
TABLE 2
Haplotype frequencies (HFI with significant delta ualues (d
! and association coefficients (rl
Milwaukee Poles and Germans
Poles
Haplotype
HF
Al-B8
A3-B7
A25-Bl8
A29-Bl2
AW30-Bl3
0.166
0.074
0.046
0.046
0.034
Germans
_-__
A
0.116***
ns
0.034***
0.035"'
0.023'
LR
r
HF
0.66
ns
0.32
0.36
0.21
0.137
0.121
0.011
0.037
0.021
Significant levels of gametic associations are indicated with aaterisks
* p < 0.01.
** p < 0.001.
*** p < 0.0001.
ns, not significant.
A
0.085**'
0.054**
na
0.025*
0.016*
r
0.47
0.27
ns
0.22
0.22
21
HLA ANTIGENS IN POLES AND GERMANS
2). The association between A1 and B8 was
most extreme in both Poles and Germans as
evidenced by high A values (0.116 and 0.085)
and association coefficients (r = 0.66 and r =
0.47). Haplotypes A 2 9 - B l 2 and AW30-Bl3
were also found in significant linkage disequilibrium in both populations. In contrast, the
haplotype A25-Bl8 had signficant h and r
values in Poles (P < 0.0001) but not in Ger-
mans. The reverse situation was observed for
A3-B7 which showed significant linkage disequilibrium only in Germans (p < 0.001).
DlSCUSSION
The results of this study show similar but
not identical distributions of HLA antigens in
Milwaukee Poles and Germans. They are comparable to data obtained with other major Eu-
TABLE 3
Gene frequencies o f HLA antigens in Central and Eastern European populations
Slavs
Germans
HLA antigens
HLA-A locus
A1
A2
A3
A9
A10
All
Awl9
AW23
AW24
A25
A26
A28
A29
AW30
AW31
AW32
AW33
Blank A
HLA-B locus
B5
B7
B8
B12
B13
B14
B15
BW16
B17
B18
BW21
BW22
B27
BW35
B37
B40
BW41
BW45
BW53
Blank B
Berlin
n = 600
Essen '
n = 255
Munich
D = 442
Hannover
n = 386
0.1585
0.2933
0.1417
0.0982
0.0844
0.0478
0.1905
0.3283
0.1495
0.1406
0.0496
0.0562
0.144
0.260
0.156
0.091
0.059
0.063
0.084
0.1408
0.3021
0.1377
0.1287
0.0518
0.0573
0.1088
-
-
-
0.039
0.033
0.0249
0.0699
-
-
0.0435
0.0258
-
-
-
Czechs
n = 267
Yugublavs
n - 178
0.1291
0.2656
0.1454
0.1131
0.1036
0.0608
0.0351
0.051
0.0389
0.1531
0.2765
0.1274
0.1306
0.0752
0.0562
0.0764
0.0214
0.1092
0.0174
0.0578
0.0436
0.0243
0.0139
0.0139
0.0243
-
-
-
-
-
-
-
-
0.0519
0.0283
-
0.0068
-
0.1326
0.0596
0.083
0.1015
0.0611
0.0350
0.0709
0.1150
0.1084
0.1169
0.0305
0.0248
0.0549
0.0569
0.1668
0.1376
0.1345
0.0508
0.0448
0.0376
0.0782
0.1483
0.0924
0.1392
0.0303
0.0369
0.0924
0.0619
0.0435
0.0135
0.0455
0.0735
0.0217
0.0297
0.0566
0.068
0.152
0.100
0.122
0.040
0.017
0.063
0.017
0.039
0.042
0.025
0.016
0.037
0.080
0.0519
0.1005
0.0789
0.0912
0.0284
0.0198
0.0548
0.0256
0.0342
0.0881
0.0430
0.0441
0.0608
0.1553
0.071
0.0768
0.0805
0.1178
0.0955
0.0985
0.0521
0.0169
0.0564
0.0347
0.0424
0.0462
0.0191
0.0323
0.0822
0.1052
0.0019
0.0626
0.0095
-
-
-
0.2133
' M e n d and Richter, '72.
' Bertram8 et al., '71.
Albert et al., '72.
' Gleichman, '74.
' lenhart et al., '77.
Kastelan et al.. '74.
-
+
' Singal and Bhargava. '75.
-
-
-
-
-
-
0.0463
0.111
-
0.0289
0.0026
0.0259
0.0065
0.0410
0.0782
-
-
0.1353
-
0.0462
Canadian
Ukrainians
n - 93
0.18
0.33
0.06
0.13
0.11
0.06
0.08
0.01
0.11
0.06
0.04
0.04
0.01
0.02
0.02
0.02
0.01
0.01
0.14
0.10
0.06
0.12
0.07
0.02
0.02
0.06
0.03
0.08
0.02
0.02
0.05
0.0460
0.08
0.03
0.03
-
0.01
-
0.1066
-
0.05
.
22
JOAN C. STEVENSON AND RENk J. DUQUESNOY
ropean populations (Bodmer et al., '711. Gene
frequencies for nearby Eastern and Central
European populations are presented in table 3.
Data is lacking for certain alleles for several
of these populations because many reagents
were unavailable a t the time of study. Our
findings of gametic association between A1
and B8 and between A29 and B12 were not
surprising since linkage disequilibrium for
these antigens have been reported for most
European Caucasoid populations (Bodmer et
al., '72; Degos and Dausset, '74). In both Poles
and Germans we found gametic association
between AW30 and B13. This association has
not been extensively reported for Europeans
(Bodmer, et al., '72) though i t is believed that
the AW30-Bl3 haplotype is common to middle
Eastern populations (Degos and Dausset, '74).
The gametic association A3-B7, which is common to northern European populations (Degos
and Dausset, '741, was also observed in Milwaukee Germans but not in Poles. Strong
linkage disequilibrium between A3 and B7
has previously been reported in Germans in
Berlin (Menzel and Richter, '721, Munich (Albert et al., '721, Essen (Bertrams et al., '711, in
Hannover (Gleichmann, '74).
Milwaukee Poles showed significant gametic association between A25 and BIB. High A
values for the A25-Bl8 haplotype have also
been reported for population groups of
Slavonic origin such as Ukrainians (Singal
and Bhargava, '751, Yugoslavs (Kastelan e t
al., '74) and Czechs (Lenhart et al., '77). In
contrast, a significantly increased frequency
of the A25-Bl8 haplotype was not found in
Milwaukee Germans, nor has it been reported
in Germans living in Berlin, Essen and Hannover. Significant gametic association between A10 and B18 has been reported for Germans in Munich (Albert et al., '721, but it is
not known whether the association with B18
was for A25 or A26.
The high frequencies of the A25-BI8 haplotype in Poles, Ukrainians, Yugoslavs and
Czechs suggest that the spread of Slavonic
culture included population movements and
that the haplotype A25-Bl8 may be a slavonic
marker,
ACKNOWLEDGMENTS
Supported by Contract HL-73-2956 and
Grant AI-12507 from the National Institutes
of Health. We thank the students of Pulaski
High School, Milwaukee and, the Polish
Women's Culture Club.
LITERATURE CITED
Albert, E. D., S. Schols, I. Rosenthal, €I. Baltin and J. Bertram's 1972 Study of t h e HL-A system in the Turkish
and German populations. In: Histocompatibility Testing
1972. J. Dausset and J. Colombani, eds. Munksgaard,
Copenhagen, pp. 147-152.
Bertrams, J., I. Kuwert and U. h h m e 1971 H L A phenotype and gene frequencies in the German Ruhr area populations. European J. of Immunol., 1: 306-309.
Bodmer, J. R., P. Rocques, W. F. Bodmer, J. Colombani,
L. Degos, J. Dausset and A. Piazza 1972 Joint Report of
t h e First Histocompatibility Workshop I Population
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Cavalli-Sforza, L. L., and W. F. Bodmer 1971 The Genetics
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195-210.
Faust, A. B. 1927 The German Element in the I J S . The
Steuben Society of America, New York.
Gleichman, H. 1974 IIL-A phenotype and haplotype frequencies in a German population. Tissue Antigens, 4:
157.165.
Gregory, J. G . 1931 History of Milwaukee, Wisconsin, S. J.
Clarke Pub. Co., Chicago.
Kastelan, A., V. Kerhin-Brkljaac, J. Hors, L. Brkljaac and
P. Macasovic 1974 The distribution of HIJ-A antigens
and genes in t h e Yugoslav population. Tissue Antigens, 4:
69-75.
Kissmeyer-Nielsen, F. 1975 Histocompatibility Testing
1975 Munksgaard, Copenhagen.
Lenhart, K., A. Bartova and E. Lenhartova 1977 HLA genetic structure of population in the district of Olomouc
(Czechoslovakia). Tissue Antigens, 9: 220-222.
Mattiuz, P. I., 0. Ihde, A. Piazza, R. Ceppellini and W. F.
Bodmer 1970 New approaches to t h e population genetic and segregation. Histocompatibility Testing 1970,
pp. 193-205.
Menzel, G. R., K. V. Richter 1972 The distribution of t h e
HL-A antigens and genes in a German population. Tissue
Antigens, 2: 287-292.
Milwaukee Writers Project 1947 History of Milwaukee
County. Milwaukee Public Library, Milwaukee.
Ray, J. G., D. B. Hase, P. D. Pedersen and E. E. Kayhoe, eds.
1976 Manual of Tissue Typing Techniques. DHEW Puhlication No. (NIH) 75-545, Bethesda, Maryland.
Schrieber, H. 1965 Teuton and Slav, the Struggle for Central Europe. Constable and Co., Ltd., London, England.
Singal, D. P., and A. Bhargava 1975 The distribution of
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Munksgaard, Copenhagen, pp. 188-192.
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