close

Вход

Забыли?

вход по аккаунту

?

Gc (vitamin D binding protein) subtype polymorphism and variants distribution among Saharan Middle East and African populations.

код для вставкиСкачать
AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 52435-441 (1980'
Gc (Vitamin D Binding Protein) Subtype Polymorphism and
Variants Distribution Among Saharan, Middle East, and
Af r i can Popu I at io ns
J . CONSTANS, Ph. LEFEVRE-WITIER, P. RICHARD, A N D G. JAEGER
Centre dHemotypologie du C.N.R.S., CHU Purpan, 31052 TOULOUSE
CEDEX (J.C., Ph.L.-W., P . R . ) Centres Europeens Assoads de Biologie
Humaine, HGpttul Cochin, 75014 PARIS (G.J.)
KEY WORDS Gc, VDBP, Polymorphism,
Isoelectrofocusing, Sahara, Middle East, Africa
ABSTRACT
This article presents the results obtained by electrophoretic
analysis of the group specific component polymorphism in more than 1,250 serum
samples from populations living in the Sahara, the Middle East, and equatorial
Africa. In addition to the alleles GcIt and Gels, five variants, including one previously unknown, were found. The distribution of the alleles herein described permits speculation on exchanges and relations among the groups considered. The
lowest frequencies of the gene Gc' correspond to regions where sunlight is stronger.
There is also a north-south gradient in the Gclb gene frequency. This seems to
parallel the gradient seen in skin pigmentation.
The study of serum protein polymorphisms
by electrophoretic techniques has become a
valuable tool for the modern physical anthropologist. It contributes to the description of
genetic stocks, helps to trace migrations and
exchanges, and may confirm the genetic isolation of some groups. As more refined techniques
have developed, a large number of new alleles
have been demonstrated in many serum protein systems. This permits a more precise definition of a population's genetic composition.
When many populations have been studied,
maps can be drawn showing the distribution of
the various alleles. If these maps show that
clines of gene frequencies cross linguistic, cultural, and racial barriers but are correlated
with geographical factors, one can suppose an
environmental (selective) effect which may be
a s important as migration and genetic exchanges (Bodmer and Cavalli-Sforza, '76).
The determination of the polymorphism of
the serum group specific component is a good
example of such analysis. Recently, Daiger et
al. ('75; '77) showed that this protein is capable
of binding vitamin D, and many other experiments have confirmed this (Van Baelen et al.,
'78; Haddad and Walgate, '76). At the same
time, we have been able to discover the existence of the extensive polymorphism of this
protein by developing a sensitive technique of
0002-9483/80/5203-0435$01 70
11
1980 ALAN R. LISS, INC
isoelectrofocusing and immunofixation (Constans et al., '78a). Differences in the 25-OH
vitamin D:, affinity of the protein produced by
the GclF,GcIS,and Gc' alleles have been demonstrated by means of analytical isoelectrofocusing (Constans et al., '79b).
The metabolic role of the protein and its
polymorphism contribute to its importance in
clinical and biochemical research. In addition,
the fact that we observed different frequencies
of the Gc genes in European, African, and
South Amerindian groups (more than 3,000
samples studies in the laboratory) makes a
knowledge of the genetic composition of a population imperative in studies of many disease
states.
This paper presents original data obtained in
the study of the Gc polymorphism in Saharan,
Middle-East, and African populations.
MATERIAL AND METHODS
In Near and Middle East, we examined 58
sera from a group of Kurds living in Iraq and
135 sera from agricultural communities of
Bedouins who have settled in North Yemen. In
Sahara and Sahel, it is necessary to distinguish
three samples (Fig. 1):northern Algerian Sahara (Berber-speaking Harratines of the
Received May 10, 1979. accepted Septemher 18. 1979
435
436
J. CONSTANS, Ph. LEFEVRE-WITIER, P. RICHARD, AND G. JAEGER
Fig. 1. Location of the eight groups that a r e the subject of this work.
Saoura valley), central Algerian S a h a r a
(Twareg Isseqamarens of the Hoggar), and
southern Sahara (Twareg Kel Kummer of
Mali). In eastern Africa, we studied several
families from the Afar (95persons) and Issa (92
persons) ethnic groups. In equatorial Africa, we
examined samples from the Sara (291persons)
who are farmers living in a savannah region of
the Central African Empire.
Each serum was simultaneously studied by
two techniques according to the recommendations of the recent Gc workshop (Constans
and Cleve, '79a): isoelectrofocusing on polyacrylamide gel 1 mm thick prepared with an
Ampholine solution (LKB) a t pH 4.6 and electrophoresis on polyacrylamide gel. After electrophoresis, proteins a r e stained using a
coomassie blue solution. After IEF, an immunofixation on cellulose acetate is necessary.
The sera, conserved a t -2O"C, showed no bacterial degradation. All but one of the variants
found during this study have already been described (Constanset al., '78a, b). The transmission of the new variant was confirmed by family
studies.
The results of this research are expressed,
not according to the traditional nomenclature
based on the diallelism of Gcl and Gc', but ac-
cording to the recommendations of the International Workshop on Gc Protein. In Figure 2, we
show the variants known a t this time with the
correspondences between the old and the new
nomenclatures.
The genotype distributions were calculated
by t h e maximum likelihood programm
(Laudet, '68) according to codominant and autosomal transmission of the different alleles
considered. The x 2 values were obtained by
comparison between the numbers observed and
expected in each genotype class. The degree of
freedom for each sample was determined by
subtracting the number of genes in the population (variant excluded) from the number of
phenotypes expected, disregarding any phenotype classes with less t h a n five members
(Schwartz, '77).
RESULTS AND DISCUSSION
The distribution of the observed phenotypes
and of the genetic frequencies obtained are
presented in Tables 1 and 2. These data show
t h a t , based on the diallelism Gcl-GcY,the
genotypic and phenotypic frequencies of these
groups are similar to those given in the literature for the neighboring geographic zones
(Cleve, '73).
Gc SUBTYPES AND VARIANTS-SAHARA, MIDDLE EAST, AFRICA
A: 2-1F
1C
1V2
1F
1Ab
1s
B: 2-IF
1A6
1A5
IF
1Al
1s
1C3
2A5
2A3 2
Fig. 2. Isoelectrofocusing gel electrophoretic patterns of
Gc subtypes and variants. Lane A corresponds to the usual
denomination for Gc variants. Lane B corresponds to the new
nomenclature adopted after the recent Gc workshop ( 7 )
which makes reference to the anodal or cathodal mobilities of
the different bands. A set of two bands is a Gc' variant, while
a single band is a Gc' variant.
However, neither electrophoretic techniques
have shown that the diallelism system is incomplete. In fact, there are three principal alleles in the Gc protein: Gcl", Gc'?,and Gc2.The
electrophoretic mobilities of their protein
products were described earlier (Constans and
Cleve, '79a) and are compared to the variants
detected in this study (Fig. 2 ) . A total of twenty
nine variants are known to date. According to
the usual definition, a variant is a n allele present at less than 0.01 frequency in a population
(Neel, '78).
The deviation between the number of individuals observed and expected in each
phenotype (Table 2), assuming Hardy-Weinberg equilibrium, is small. Only the result obtained in the Afar and North Yemen groups
show elevated xs values corresponding to a difference between the observed and expected
heterozygotes Gc 2-1sand Gc-2-IF. The difference is a t the limit of significance (0.02 <p <
0.05). We have observed a similar distribution
of the Gc'" and Gc"' genes in the Peulh population of Senegal (Constans et al., '78b). Only
genetic studies done on families and on a larger
population sample will allow us to distinguish
between the effects of selection and chance. The
high value of the x' expresses an anomaly in the
population studied and cannot be explained by
inbreeding alone. The Kel Kummer Twareg
sample is an example of a population in which
we have obtained a low x' value showing a good
repartition, although this population is known
437
to be very inbred (Jacquard, '72; LefevreWitier, '74). In this group, descended from a
very small number of ancestors, we notice the
absence of the Gc' gene, which can be explained
by the founder effect or by genetic drift.
In other respects, the Kel Kummer can be
regarded as belonging to the same genetic stock
as the surrounding populations of the North
Sahara. Since we have described that Gcl is
actually made up of two alleles, we can see that
this group has maintained a Gc polymorphism.
Without modern electrophoretic techniques,
this would not have been evident (Constans et
al., '78a).
The Gc", G P , and Gc' gene frequencies in
the samples studied permit a division into three
groups: First, there is the group made up of the
populations of the northern Sahara, the Sahel,
and East Africa (Djibouti samples), where the
frequency of the gene Gc" is almost equal to
that of the gene Gc'"; Second is the Twareg Kel
Kummer genetic isolate, among whom the Gel"
gene frequency is the highest yet known, and
the Twareg Isseqamaren tribe whose Gcl" gene
frequency is also superior to that of Gclt; Third,
the Sara group (CAE) shows a Gc" gene frequency substantially higher than that of Gels.
We have also observed such values in the
Peulhs of Senegal (Constans et al., '78b) and
among the Bi-Aka Pygmies (Constans et al.,
'78a).
In the Gc system, European populations are
characterized by a Gc' gene frequency greater
than 0.25 and a frequency of Gc'" greater than
Gc" (Constans et al., '78c; Cleve et al., '78;
Kiihnl and Spielman, '78; Thymann and Henningsen, '78). The comparison between the European pattern and the data presented here
contrast (Fig. 3).The populations of Europe and
of black Africa represent the extremes on this
graph and between these two extremes, the position occupied by other samples is especially
interesting: The Afar and Issas groups are located not far from the populations of the Middle
East, with a frequency of the gene Gc' greater
than that of other African populations. However, the frequencies of their Gc'" and Gc'"
genes are closer to those of the Twareg and
Berber Arab groups of the Sahara. The Kurds
and the Bedouins of North Yemen have Gcl"
gene frequencies approaching those of European populations, while their Gc' gene frequencies distinguish them clearly from those
groups.
Clusters of populations can be seen in Figure
3. They correspond well to the geographical
clustering of the same populations within the
438
J. CONSTANS, Ph. LEFEVRE-WITIER, P. RICHARD, AND G. JAEGER
0.481
0.425
161
160
Harratins and
MRabtines (Saoura)
Tuareg Isseqamaren
(Hoggar)
260
357
291
751
Tuareg Kel Kummer
(Menaka)
Peuhls (Fula)
Sara
Pygmies Biaka
Mali
Senegal
Empire Of
Central
Africa
Algeria
0.619
0.835
0.182
0.091
0.115
0.780
0.039
0.005
0.027
-
0.074
-
-
0.053
0.069
2.89
4.81
0.082
0.010
0.015
0.058
0
-
-
0.008
-
0.677
2.52
0.015
2.55
2.87
7.24
2.74
7.17
XZ
0.003
0.054
0.125
0.179
0.172
0.137
Gc2
-
0.016
0.541
-
-
-
-
0.010
0.005
-
-
0.446
-
-
&‘A5
-
\I
0.008
0.004
&I
0.005
0.008
0.430
0.315
0.430
92
Issa
of
Djibouti
0.358
0.463
95
Afar
Republic
0.595
0.589
0.224
0.270
58
135
Kurds
Miscellaneous
Iraq
North Yemen
&”
&IF
N
Population
Country
Gc Gene Frequencies
TABLE 2. Frequency of Gc“, Gc”, GcZ, and Gc vanants in Middle East, S a h m n , and African groups
(0
w
b
P
“e
M
M
F
5U
7
i
-5
21
>
??
%U
4
k?
2
d
n
440
J. CONSTANS, Ph. LEFEVRE-WITIER, P. RICHARD, AND G. JAEGER
Gc Is gene
frequencies
t
'Itsa
'Afar
q21
Fig, 3. Distribution of the eight groups which are the subject of this work according to their Gc" and Gc'gene
frequencies and in comparison to other data puhltshed.
clusters, the groups of the Sahara differ more
by their Gc" gene frequencies, while in Europe
the groups differ more by their GcLgene frequencies. Based on the existence of the three
gene Gc", Gc" and Gc', it is interesting to
notice such variability in the manifestation of
the polymorphism.
These data reveal certain phenomena which
perhaps can be best explained by the action of
geographical factors in relation to the metabolic role of this protein in the organism (Daiger and
Cavalli-Sforza, '77; Constans et al., '79b). Kirk et
a l . ('63), Walter and Steegmuller ('691,
Mourant et al. ('76), and later Daiger ('79)have
demonstrated that the frequency of the gene
Gc2 follows a cline, diminishing a s the mean
intensity of solar radiation increases. Our results confirm this assumption. The data recovered in this investigation show the presence of a
gradient in the frequency of the gene Gel'
which increases from Europe t o equatorial Africa. This gradient may be superposed on that
of skin pigmentation (Loomis, '67) which has
always been considered to be linked to genetic
and adaptative conditions (Hiernaux, '77).
Distribution of vuriunts
The study of these samples has permitted us
to discover one new variant, Gc' \Ii, in the Issa
group. The other variants Gel.\' (Gc""), GclC':',
Gc2.':<,Gc''.'~have already been described (Constans and Cleve, '79a).
We observe that the variant Gc'." is present
in the Kurds of Iraq, the Yemenites, the Sara
samples, the Peulhs, and in the Harratins ofthe
Saoura. Earlier studies suggested that the
presence of the Gcl.'l variant was limited to the
populations of sub-Saharan Africa, especially
Bantus (Kitchin and Bearn, '66) or Pygmies
(Constans et al., '78a). Its presence a t a low
frequency among our different samples of
Kurds, Yemenites, Sara, Fulani, and Harratins
of the Saoura valley suggests a n introduction
through contacts or the slave trade. This could
also explain the presence of the negroid Gc"':' in
two Harratin individuals (Algerian Saoura).
Another variant, Gc"':', could be a good
marker for populations of the Sahara and the
Near East (Druzes studied by Cleve et al., '78).
We found it in two Twareg samples in the Issas
of Djibouti and the Fulani of Senegal (Constans
Gc SUBTYPES AND VARIANTS-SAHARA, MIDDLE EAST, AFRICA
et al., '78b). Up to this date, it has not been
found in European and sub-Saharan samples.
The G C " ~variant is also found in the Saharan
populations, but has only been found in the
small isolated tribe of Isseqamaren Twareg and
the Fulani of Senegal.
CONCLUSIONS
Group specific component polymorphism, as
studied by modern electrophoretic techniques,
represents an extremely instructive marker
system for anthropological research. The frequencies of the Gc alleles and their presence or
absence in the populations presented in this
paper help us t o evaluate the population dynamics of North Africa and the Arabian peninsula. Every human population studied to date
is polymorphic for the Gc protein. Even in the
Kel Kummer, who were completely lacking the
Gc' allele, a polymorphism is present, because
the Gc system is multiallelic. The distribution
of the Gc alleles seems to correlate with geographical clines, notably the incidence of solar
radiation, as might be expected for the protein
which transports vitamin D.
LITERATURE CITED
Bodmer, W.F., and L.L. Cavalli-Sforza, (1976) Genetics,
evolution, and man. W.H. Freeman, San Francisco, pp.
718-723.
Cleve, H. (1973) The variants of the group specific component. A review of their distribution in human populations.
Israel. J. Med. Sci., 9,1133-1146.
Cleve, H., W. Patutschnick, S. Novo, and G.C. Wendt (1978)
Genetic studies on the Gc subtypes. Hum. Genet. 44,117122.
Constans, J.,M. Viau, H. Cleve, G . Jaeger, J.C. Quilici, and
M.J. Palisson (1978a) Analysis of the Gc polymorphism in
human populations by isoelectrofocusing on polyacrylamidegels. Demonstration of subtypesofthe&' alleleand
of additional Gc variants. Hum. Genet., 41153-60.
Constans, J., M. Viau, G. Pison, and A. Langaney ( 1978bl Gc
subtypes demonstrated by isoelectric focusing: Further
data and description of new variants among an African
sample (Fula) from Senegal. Jap. J. Hum. Genet.,23: 111117.
Constans, J., M. Viau, and J. Ruffle ( 1 9 7 8 ~Etude
)
de la
proteine Gc dans quelques echantillons de populations en
France. Polymorphisme genetique par isoelectrofocalisation e t donnees quantitatives. C.R. Acad. Sci. (Paris),
287: 1003-1006.
Constans, J.,andH. Cleve (1979a)Group specificcomponent.
Report on the first international workshop. Hum. Genet.,
48:143-149.
Constans, J.,M. Viau, J.P. Moatti, and J.L. Clavere (1979b)
Serum vitamin D binding protein and Gc polymorphism.
In Normann, A.W., K. Schaefer, et al.: Vitamin D basic
research and its clinical application. Walter de Gruyter,
Berlin, pp. 153-156.
441
Daiger, S.P., M.S. Schanfield, and L.L. Cavalli-Sforza 11975)
Group specific component (Gc) proteins bind vitamin D
and 25 hydroxy vitamin D. Proc. Nat. Acad. Sci. (USA),
72: 2076- 2080.
Daiger, S.P., and L.L. Cavalli-Sforza (1977) Detection of
genetic variation with radioactive ligands. 11. Genetic variants of vitamin D. Labelled group specific component (Gc)
proteins. Am. J. Hum. Genet., 29:593-604.
Daiger, S.P. (1979)Biologic significance of genetic variation
in human group specific component (Gc). The plasma vitamin D binding protein. Abstracts. IVth Workshop on
Vitamin D, Berlin, February 18-22.
Haddad, J.G., and J. Walgate (1976) 25 hydroxyvitamin D
transport in human plasma. Isolation and partial characterization of calcifidiol binding protein. J. Bioch. Chem.,
252, (16):4803-4809.
Hiernaux, J . (1977) Long term biological effects of human
migration from the African savanna to the equatorial
forest: A case study of human adaptation to a hot and wet
climate. In: Population Structure and Human Variation.
G.A. Harrison, ed. Cambridge University Press, Cambridge, pp. 187-217.
Jacquard, A. 11972)Un isolat du Sud Sahara. Les Kel Kummer. 11. Evolution du patrimoine genetique des Kel Kummer. Population, 4-5,784-800.
Kirk, R.L., H. Cleve, and A.G. Bearn ( 1963)The distribution
of the group specific component (Gc) in selected populations in South and South East Asia and Oceania. Acta
Genet. (Basel)13:140-149.
Kitchin, F.D., and A.G. Bearn (1966) The electrophoretic
patterns of normal and variant phenotypes of the group
specific (Gc) components in human serum. Am. J. Hum.
Genet. 18,201-214.
Kiihnl, P., and W. Spielmann (1978)Gc subtypes in a german
population. First International Workshop on the Gc protein. XVIIth International Congress of Haematology,
Paris.
Laudet, M. (1968)Le systkme Gm en bio-anthropologie. Contribution a I'etude des methodes de calcul des frequences
geniques (These d e Doctorat, Faculte de Medecine,
Toulouse).
Lefevre-Witier, Ph. (19741Un isolat du sud Sahara: les Kel
Kummer. VI. Structure genetique des systkmes sanguins
erythrocytaires et seriques. Population, 3.518- 527.
Loomis, W.F. (1967) Skin-pigment regulation of vitamin D
biosynthesis in man. Science, 157:501- 506.
Mourant, A.E., D. Tills, and R. Domaniewska-Sobczak
(1976) Sunshine and the geographical distribution of the
alleles of t h e Gc system of plasma proteins. Hum. Genet.,
33:307-314.
Neel, J.V. (1978) Rare variants, private polymorphisms, and
locus heterozygosity in Amerindian populations. Am. J.
Hum. Genet., 30:465-490.
Scharwtz, D. (1977) Methodes statistiques a l'usage des
m d e c i n s e t des biologistes. Flammarion Medecine Sciences, Paris, pp. 93-96.
Thymann, M., and R. Henningsen (1978) Subtypes of Gc
(Group specific component) in Denmark determined by
isoelectrofocusing immunofixation and a description of
some Gc variants using this technique. First International
Workshop on the Gc Protein. XVIIth International Congress of Haematology, Paris.
Walter, H., and H. Steegmuller (1969) Studies on the geographical and racial distribution of the Hp and Gc
polymorphisms. Hum. Hered., 19:209-221.
Van Baelen, H., R. Bouillon, and P. de Moore (1978) The
heterogeneity of human Gc globulin J . Biol. Chem.,
253,6344- 6345.
Документ
Категория
Без категории
Просмотров
4
Размер файла
452 Кб
Теги
population, distributions, east, among, saharan, subtypes, vitamins, polymorphism, africa, protein, variant, binding, middle
1/--страниц
Пожаловаться на содержимое документа