The genetic position of the autochthonous subpopulation of Northern Navarre (Spain) in relation to other basque subpopulations. A study based on GM and KM immunoglobulin allotypes

GM and KM immunoglobulin (Ig) allotypes were tested in 118 autochthonous Basques from northern Navarre. The results are compared to those obtained for the same genetic markers in 6 other Basque subpopulations, 3 from Spain (Guipúzcoa, Vizcaya, and Alava) and 3 from France: Macaye, Saint-Jean Pied de Port, and Mauleon. The northern Navarrese appear genetically closer to the Alava and Saint-Jean Pied de Port subpopulations. The Basques present 3 GM haplotypes that are uncommon in Caucasian populations, suggesting that they have not been completely isolated either from Asian or African populations. The GM*1,17 23' 10,11,13,15,16 north Asian haplotype was probably the first to be introduced into the Basque area. The GM*1,17 23' 5* haplotype, considered an African genetic marker although also detected in Central Asia, would have reached the Iberian Peninsula through consecutive historic migrations from North Africa. The rare haplotype GM*1,17 23 21,28 results probably from a genetic recombination or crossing-over between the 2 common haplotypes GM*1, 17 23' 21,28 and GM*3 23 5*. It is also found with a low frequency in other neighboring regions and countries; but the possibility of its having been introduced through the main passage connecting western France and Spain during the Roman Empire and Middle Ages cannot be ruled out.     

The maternal legacy of Basques in northern navarre: New insights into the mitochondrial DNA diversity of the Franco-Cantabrian area

Autochthonous Basques are thought to be a trace from the human population contraction that occurred during the Last Glacial Maximum, based mainly on the salient frequencies and coalescence ages registered for haplogroups V, H1, and H3 of mitochondrial DNA in current Basque populations. However, variability of the maternal lineages still remains relatively unexplored in an important fraction of the Iberian Basque community. In this study, mitochondrial DNA diversity in Navarre (North Spain) was addressed for the first time. To that end, HVS-I and HVS-II sequences from 110 individuals were examined to identify the most relevant lineages, including analysis of coding region SNPs for the refinement of haplogroup assignment. We found a prominent frequency of subhaplogroup J1c (11.8%) in Navarre, coinciding with previous studies on Basques. Subhaplogroup H2a5, a putative autochthonous Basque lineage, was also observed in Navarre, pointing to a common origin of current Basque geographical groups. In contrast to other Basque subpopulations, comparative analyses at Iberian and European scales revealed a relevant frequency of subhaplogroup H3 (10.9%) and a frequency peak for U5b (15.5%) in Navarre. Furthermore, we observed low frequencies for maternal lineages HV0 and H1 in Navarre relative to other northern Iberian populations. All these findings might be indicative of intense genetic drift episodes generated by population fragmentation in the area of the Franco-Cantabrian refuge until recent times, which could have promoted genetic microdifferentiation between the different Basque subpopulations.     

Structuring the genetic heterogeneity of the Basque population: a view from classical polymorphisms

In this study we analyze 18 classical polymorphisms (ABO, Rh, MNSs, Lewis, P, Duffy, Kell, ADA, ESD, PGM1, PGD, AK1, ACP1, GLO1, HP, GC, TF, and PI) in over 2000 autochthonous individuals from 14 natural districts in three provinces of the Basque Country (Alava, Guipuzcoa, and Biscay). Heterogeneity analysis via the chi2 test and a calculation of F(ST) indicate that there is significant genetic heterogeneity between the Basque districts. The R matrix informs us that this heterogeneity is not significantly concentrated in a single district or in the districts of a single province, but is rather distributed among several districts belonging to the three provinces analyzed. We undertake to assess the influence of various historical, geographical, and cultural factors on the genetic structure of the Basque population. Analysis suggests that allele distribution is geographically patterned in the Basque Country. The gradient distributions observed in the case of some alleles (ABO*O, RH*cDE, RH*cde, MNS*MS, and ACP1*C) on the basis of Moran's autocorrelation coefficient I, along with the influence of the two main travel routes through the Basque Country (western route through Bilbao and eastern route through Vitoria), suggest that the gene flow tends toward the coast. As regards other factors considered (administrative division, repopulation processes, linguistic heterogeneity, and north vs. south cultural heterogeneity), we detected only a certain influence exerted by an old tribal differentiation (2000 B.P.), which would diminish with the passage of time.     

Study of red blood cell and serum enzymes in five Pyrenean communities and in a Basque population sample

Until recently, no data on genetic polymorphisms in the populations living on the northern side of the Pyrenees have been available, except for the Basques. Several investigations were done lately on rural communities in various geographic zones in the Pyrenees from the eastern to the western part. In this paper, the results for the following enzyme polymorphisms are reported: acid phosphatases, AK, ADA, PGM1 and PGM2, 6PGD, NADH diaphorase, SOD, MDH, TGP, G6PD, C5 esterase (E2 locus), serum cholinesterase (E1 locus). Significant variation in gene frequencies was observed over the distinct geographic zones for the main polymorphic system. Furthermore, some rare alleles were found: a new G6PD variant (Luz-Saint-Sauveur), the presence of ADA3 and ADA5 alleles in two groups of the Central Pyrenees, a Dia2 gene among Basques and in the Pays de Sault, a high rate of Ea1 allele in the Basque group. The values obtained for the degree of heterozygosity are in agreement with the relative isolation of the different groups studied and confirm the importance of sociocultural factors in the evolution of the genetic background of rural communities in Europe.     

Allele variation of DYS19 and Y-Alu insertion (YAP) polymorphisms in Basques: an insight into the peopling of Europe and the Mediterranean region

Two Y-chromosome DNA polymorphisms, the DYS19 microsatellite and the YAP (at locus DYS287), were tested in males from two autochthonous Basque populations from France and northern Navarre (Spain). The results are compared to those obtained for the same genetic markers in 32 populations from Europe, northern Africa, and western Asia. The high predominance of the DYS19*11 (190-base-pair) allele in Basques indicates that their genetic diversity for microsatellite DYS19 is around half that observed in Europeans, North Africans, and western Asians. The Y-Alu insertion (YAP+) was not detected in the Basque samples. This study attempts to throw some light on the importance of historically recent migratory movements, the main corridors of gene flow, and demographic sizes and their variations in shaping gene frequency patterns in contemporary human populations, particularly in the Mediterranean region. Historical processes may have had more significant effects on the genetic make-up of current human populations than those of prehistoric times.     

Genetic structure of a Sakha population from Siberia and ethnic affinities

The red cell enzymes ACP1, ESD, GLO1, PGM1 and RDS and the serum proteins GC, HP, PI, and TF were determined for samples of 150 and 144 Sakha, respectively. The Sakha, a Turkic-speaking population, inhabit the Sakha-Yakutia Republic in northeastern Siberia. High gene frequencies were found for ACP1*A, GLO1*1 and GC*1F, whereas no P1*S or P1*Z alleles were found. In addition, 1 heterozygous phenotype with ACP1*C and 2 heterozygous phenotypes with ESD*7 were found. The genetic distance measures show close affinities of the Sakha population to Buryats (especially Western Buryats), Mongols, and Evenks, whereas the genetic distance to Turkic-speaking Altay and Tuvan populations is great.     

Genetic predisposition to development of toxic liver cirrhosis caused by alcohol]

Comprehensive analysis of the contribution of genetic factors into predisposition to alcoholic toxic cirrhosis (TC) was performed. The ABO, RH, HP, TF, GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compared in 34- to 59-year-old male TC patients and control donors of the same sex and age. The phenotypic frequencies in the TC group deviated from the theoretically expected values; the main difference was the excess of rare homozygotes for the loci GC, ACP1, ESD, and GLO1. In the TC patients, the observed heterozygosity (Ho) was considerably lower than the theoretically expected value (H(e)). Wright's fixation index (F) in the TC patients was 30 times higher than in the control group (0.0888 and 0.0027, respectively). The frequencies of PI*Z and PI*S, the PI alleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group. The TC patients exhibited a significantly higher frequency of the liver glutathione-S-transferase GST1*0 allele, whereas the GST1*2 frequency was two times higher in the control subjects than in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of the following alleles of six independent loci: ABO*0, TF*C1, TF*C2, PI*M1, PI*Z, ACP1*C, PGM1*1+, PGM1*1-, PGM1*2-, GST1*0, and GST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastically lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotypes. The total and direct reacting bilirubin concentrations depended on the erythrocytic-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control groups.     

The Russian gene pool. Genogeography of erythrocyte genetic markers (ACP1, PGM1, ESD, GLO1, 6-PGD)

The study continues the series of works on the Russian gene pool. Gene geographic analysis of five erythrocytic gene markers best studied in the Russian population (ACP1, PGM1, ESD, GLO1, and 6-PGD) has been performed. Gene-geographic electronic maps have been constructed for 13 alleles of these loci and their correlations with geographic latitude and longitude. For all maps, statistical characteristics are presented, including the variation range and mean gene frequencies, partial and multiple correlations with latitude and longitude, and parameters of heterozygosity and interpopulation diversity. The maps of eight alleles (ACP1*A, ACP1*C, PGM1*2+, PGM1*2-, PGM1*1-, ESD*1, GLO1*1, and PGD*C) are shown and analyzed in detail. The genetic relief and structural elements of the maps are compared with the ecumenical trends, main variation patterns of these genes in northern Eurasia, and genetic characteristics of the indigenous populations of the Urals and Europe.     

HUMF13A01 in autochthonous Basques and in genetically related populations

A population gentics study was carried out on 678 Basque individuals using the short tandem repeat HUMF13A01. Thirteen different alleles were detected. This population is in Hardy-Weinberg equilibrium. The singularity of the Basque population’s HUMF13A01 allele frequencies is displayed in the European context, through some genetic similarities are shown, especially with some neighbouring and culturally related populations, and with other populations with which Basques may have shared ancient common roots, such as the Sardinians.     

Paternal genetic history of the Basque population of Spain

This study examines the genetic variation in Basque Y chromosome lineages using data on 12 Y-short tandem repeat (STR) loci in a sample of 158 males from four Basque provinces of Spain (Alava, Vizcaya, Guipuzcoa, and Navarre). As reported in previous studies, the Basques are characterized by high frequencies of haplogroup R1b (83%). AMOVA analysis demonstrates genetic homogeneity, with a small but significant amount of genetic structure between provinces (Y-short tandem repeat loci STRs: 1.71%, p = 0.0369). Gene and haplotype diversity levels in the Basque population are on the low end of the European distribution (gene diversity: 0.4268; haplotype diversity: 0.9421). Post-Neolithic contribution to the paternal Basque gene pool was estimated by measuring the proportion of those haplogroups with a Time to Most Recent Common Ancestor (TMRCA) previously dated either prior (R1b, I2a2) or subsequent to (E1b1b, G2a, J2a) the Neolithic. Based on these estimates, the Basque provinces show varying degrees of post-Neolithic contribution in the paternal lineages (10.9% in the combined sample).     

Red cell enzyme polymorphisms in Friuli Venezia Giulia (northeast Italy)

Seven erythrocyte enzyme polymorphisms (ACP1, ADA, ESD, GLO1, PGD, PGM1 and PGM2) were investigated in a sample of 673 unrelated adult individuals from Friuli Venezia Giulia (or Friuli) and Istria. The gene frequencies found in the four provincial samples of Friuli and Istria fall within the range previously reported for Italy, showing a genetic homogeneity among the considered samples. However, comparisons with data from ex-Yugoslavian samples--using the chi 2 test--showed rather marked differences, probably due to a real different genetic structure of the compared samples. A significant association was found assuming a linear relation between the ADA*2 allele frequencies and longitude (r = +0.5503) and between the PGD*C frequencies and latitude (r = -0.6483), suggesting the existence of a clinal trend for these allele frequencies in Italy. These results seem to disagree with foregoing conclusions stated by other authors, probably because these studies were carried out in an area either rather narrow from the geographical point of view or affected by small size migration movements.     

DNA polymorphisms detect ancient barriers to gene flow in Basques

This work features the first district-by-district analysis of all provinces in the Iberian Peninsula with an autochthonous Basque population, and indicates the existence of genetic heterogeneity. The populations cluster in three groups arising from processes of genetic drift which probably occurred in pre-Mesolithic times, and were probably those which repopulated the southern areas of the Basque Country after the Last Glacial Maximum. It seems that from that period onwards, the population settled in three major groups (West Basques, Central Basques, and East Basques), along geographical axes which appear substantial in the maintaining of each population unit. This genetic structure is probably reflected in other aspects such as the existence of ancient tribes and the dialects of the Basque language, the boundaries of which may be related at origin and which are quite similar to those detected in this work. Our results indicate that the populations of the Basque Country are genetically close to other neighboring populations, such as that of Aragon, which may indicate an outgoing gene flow from the Basque area down the River Ebro towards the Mediterranean seaboard. While our short tandem repeat data suggest that population structure within the Basques dates back to the Mesolithic, our findings are also consistent with the hypothesis that patterns of modern European genetic diversity have been shaped mainly during the Neolithic.     

To the research of the gene pool of the Gagauz population of Moldavia

Population genetic data on Gagauzes from Moldavia are reported here for the first time. AB0 and Rhesus blood groups, serum protein group (HP, TF, GC) and the red cell enzyme polymorphism PGM1 were determined in 190 Gagauzes. In addition to this the ability to taste PTC was tested. The following allele frequencies were found: AB0*0 = 0.5241, AB0*A = 0.3279, AB0*B = 0.1480; RH*D = 0.6083, RH*d = 0.3917; HP*1 = 0.3544, HP*2 = 0.6456; TF*C1 = 0.7472, TF*C2 = 0.1770, TF*C3 = 0.0730, TF*B = 0.0028; GC*1F = 0.1025, GC*1S = 0.5932, GC*2 = 0.3043; PGM*1+ = 0.5932; PGM*1- = 0.1000, PGM*2+ = 0.2607, PGM*2- = 0.1107. The frequency of the PTC*T allele was found to be 0.5298. These frequencies and genetic distance analyses show that the gene pool of the Gagauzes is similar to that of neighbouring southeastern European populations.     

An ecogenetic approach to studying the adaptation and human health]

Genetic markers--blood groups ABO, RH, MN; serum proteins HP, PI, TF, C3; erythrocyte enzymes ACP1, ESD, AK1, PGM1, GLO1, PGD, PGP; and the other: PTC-tasting, ear wax types and color vision, were studied in two aboriginal Buryatian populations of Baikal Lake region: in Chitinskaya and Irkutskaya Provinces. Two samples were further divided into subgroups, according to their health status: "healthy", "indefinite" and "sick" by means of special regression procedure. The "healthy" subgroup of the Chitinskaya Province population is characterized by higher frequencies of PTC-tasters: 0.871 vs. 0.757 in the "sick" part (chi 2 = 5.36, p less than 0.05); higher frequency of the phenotype PI M1M1: 0.734 in "healthy" vs. 0.547 in "sick" (chi 2 = 8.89, p less than 0.01); also, lower frequency of the PI M1M2 phenotype: 0.148 and 0.299, respectively (chi 2 = 7.49, p less than 0.01); the frequencies of the phenotype TF C2C2 are: 0.015 and 0.076 (chi 2 = 5.48, p less than 0.05). In Irkutskaya Province population differences between "healthy" and "sick" subgroups were discovered for blood group AB: "healthy" 0.046 and "sick"--0.175 (chi 2 = 11.28, p less than 0.010); for GC (1F-2)--0.214 and 0.116 (chi 2 = 4.45, p less than 0.05). Some other differences between "healthy" and "sick" in both populations are not significant. Some trends concerning heterozygosity in loci--GC, PGM, TF were discovered. The results are considered from the viewpoint of higher fitness of some genetic traits in the populations studied.     

Characteristics of the gene pool of the Gagauz population of Moldova]

Population genetic data on Gagauzes from Moldova are reported for the first time. Blood groups AB0 and Rh and biochemical markers of genes HP, TF, GC, and PGM1 were determined in 190 Gagauzes. The following allelic frequencies were determined: AB0*0, 0.5241; AB0*A, 0.3279; RH*d, 0.4571; HP*1, 0.3544; TF*C1, 0.7472; TF*C2, 0.1770; TFC3, 0.0730; TF*B, 0.0028; GC*1F, 0.1025; GC*1S, 0.5932; GC*2, 0.3043; PGM1*1+, 0.5286; PGM*1-, 0.1000; PGM1*2+, 0.2607; and PGM1*2-, 0.1107. The data obtained indicate that the gene pool of Gagauzes is similar to those of neighboring southeastern European populations.     

Genetic polymorphism of the erythrocytic enzymes in the Buryat populations

Polymorphism of seven erythrocytic enzymes PGM1, ESD, CLO1, PGD and PGP were studied in five samples of Buryats. The main investment into differentiation between populations has been made by the following systems: CLO1, PGD and PGM1. Analysis of genetic distances between populations demonstrated that there was some parallelism among the genetic and anthropological differentiation in the Buryat populations. The groups of the Agingsky county (the area to the east from the Baikal Lake) have probably the largest proportion of the Caucasian genes as compared to other populations studied. One of the characteristics of the Buryats, especially for the population to the east from the Baikal Lake, is high frequency of the PGD allele. The rate of the genetic variability on the intra-population level is higher than the difference between populations. This means that the divergence between the Buryats populations is not very strong. Consideration of the genetic variability on the intra-population level seems to be more perspective for ecogenetic estimation of the adaptive genetic processes than analysis of the differences between populations studied.     

Acid phosphatase, adenosine deaminase and esterase D polymorphisms in the Spanish Basque population.

The 3 red-cell polymorphic systems acid phosphatase (ACP), adenosine deaminase (ADA) and esterase D (ESD) have been studied in a random sample of 1,112 individuals from the Basque country: The allelic frequencies obtained were ACP*A = 0.275, ACP*B = 0.718 and ACP*C = 0.007; ADA*2 = 0.021, and, ESD*2 = 0.066. The allelic frequencies have been compared with those of other Basque and other European populations. In comparison with Basques, significant differences were detected only for ACP, whereas as regards other Europeans significant differences were obtained with practically all the populations compared for the 3 genetic systems studied. The low values of the less frequent alleles, especially that for the ACP*C allele which is the lowest reported in Europe, are noteworthy.     

Are the Basques a single and a unique population?

Different analyses of genetic polymorphisms performed on the Basque population have suggested a possible heterogeneity of the Basques and a singularity of their genetic characteristics. In this paper, both aspects are analyzed by means of the genetic study of seven polymorphic systems--ACP, ADA, AK, ESD, PGD, GC, and HP--in 854 autochthonous individuals from the province of Vizcaya. The individuals were classified as being from the regions of Arratia, Guernica, Durango, Uribe, Marquina, Lea, and Bilbao, on the basis of the birthplaces of their four grandparents. Analyses for heterogeneity of the gene frequencies distribution suggest that there is a moderate genetic heterogeneity, probably produced by centuries of geographical and administrative isolation of these regions. The comparison with caucasoid populations, performed using the principal components analysis and Cavalli-Sforza and Edwards arc distance, indicates that the subpopulations of the province of Vizcaya have experienced little genetic exchange with other caucasoids and that the distribution of their genetic frequencies differentiates them from other populations.     

Serum protein polymorphisms in Arab Moslems and Druze of Israel: BF, F13B, AHSG, GC, PLG, PI, and TF.

We report results of typing two population samples, Israeli Arab Moslems and Arab Druze, for seven serum protein genetic variants. Data are presented in comparison with results for the same markers in a sample of Jordanian Arabs. In Israeli Moslems gene frequencies for BF (n = 169) were BF*S = 0.6361, BF*F = 0.3343, BF*S07 = 0.0296, and BF*1 = 0, and for TF (n = 90) the gene frequencies were: TF*C1 = 0.7167, TF*C2 = 0.2611, and TF*C3 = 0.0222. Allele frequencies for AHSG in Israeli Moslems (n = 155) and Druze (n = 192) were AHSG*1 = 0.9129 and 0.8750 and AHSG*2 = 0.0806 and 0.1250, respectively. Gene frequencies for PLG in Moslems (n = 149) and Druze (n = 190) were PLG*A = 0.4597 and 0.5288 and PLG*B = 0.5101 and 0.4188, respectively. The typing of Israeli Arab Druze (n = 194) for F13B resulted in F13B*1 = 0.8454, F13B*2 = 0.0387, F13B*3 = 0.0979, and F13B*4 = 0.0180. Results on the same population for PI (n = 192) were PI*M1 = 0.7839, PI*M2 = 0.1276, PI*M3 = 0.0781, PI*M4 = 0.0026, and PI*M5 = 0.0026. Observed rare alleles in various systems indicate gene flow from Europe, Africa, and Asia into the Middle East. The results on Arab populations were considered in relation to available population data in the three adjacent continents. The emerging gene frequency profile for Arabs seems to fit with the central geographic and climatic position of the Middle East.     

The Russian gene pool. Frequency of genetic markers

Frequency distribution of several genetic markers was studied in ethnic Russians from the Moscow, Bryansk, Ryazan', Kostroma, Novgorod, Arkhangel'sk, and Sverdlovsk oblasts and Udmurtiya. Systems AB0, RH, HP, TF, GC, PI, C'3, ACP1, PGM1, ESD, GLO1, 6PGD, and AK were analyzed in most samples. New data on informative polymorphic genetic loci showed that the Russian gene pool mostly displays Caucasoid features. In addition, Y-chromosomal short tandem repeats (STRs) DYS19, DYS390, and YCAII were analyzed in the Russian samples. STRs of the chromosome are particularly valuable for elucidating ethnogenetic processes in Eastern Europe. Frequency distributions of the Y-chromosomal markers in Russians were intermediate between those of West European populations and eastern Finno-Ugric ethnoses of the Volga region. A marked longitudinal gradient was revealed for frequencies of several molecular markers.