Polymorphism C3435T of the MDR1 gene in Central Americans and Spaniards

The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.     

Genetic polymorphism and rare variants of alpha 1-antitrypsin in the population of Moscow. Research using isoelectric focusing on an ultrathin gel

The data are presented on distribution of subtypes and rare variants of Pi system for Moscow population. Serum samples were obtained from 210 families of healthy newborn (father-mother-newborn) from several Moscow maternity hospitals. Phenotypes of alpha 1-antitrypsin were detected by isoelectric focusing in ultrathin layer polyacrylamide gel with the range 3.5-6. In this study 5 common PiM subtypes (except M3M3) were found. The observed distribution of Pi subtypes shows a good agreement with the Hardi-Weinberg equation. The gene frequencies of the subtypes estimated for Moscow population were as follows: PiM1-0.7662, PiM2-0.1779, PiM3-0.0398. They did not show any difference from the corresponding frequencies in other European populations. In the course of our studies, some rare phenotypes, such as MS, MZ, FM and IM that were observed in most European populations, were detected. Furthermore, a very rare variant (MT) which had been only once revealed in European population, was found. The total gene frequency of all rare variants was 0.0162.     

Polymorphism of CTG-repeats in the DMPK gene in populations of Yakutia and central Asia

Allele frequency distribution of CTG-repeat in the 3'-flanking region of DMPK gene was analyzed in populations of Yakutia (three ethnogeographical groups of Yakuts, Evenks, Evens, Yukaghirs, Dolgans) and Central Asia (Kazakhs, Uzbeks, Uighurs). Frequencies of CTG alleles were found to be significantly different in two regions. Allele frequency distribution in populations of Yakutia was similar to Asian populations, whereas Central Asian populations showed similarity to European populations. The features of allele spectrum in Yakut populations were discussed in terms of high prevalence of myotonic dystrophy in Yakuts. Our result supports the hypothesis of founder effect in spread of myotonic dystrophy in Yakuts. The phylogenetic relationships between the investigated populations based on polymorphism of CTG-locus of the DMPK gene have been analyzed as well.     

Characteristics of the mitochondrial genome of russian germans]

Nucleotide sequences of the mitochondrial DNA (mtDNA) control region were studied in Germans living in the Altai, Russia. Although this ethnic group has been living in Russia for a long time, the obtained data indicate that its mitochondrial gene pool retains the main characteristics of the Western and Central European gene pools. Regarding the mitochondrial gene pool, Russian Germans were more similar to Germans living in Germany than to Russians with regard to the frequency of the Cambridge nucleotide sequence, frequencies and composition of five European haplotypic groups (classification of Richards et al.), and average intra- and interpopulation pairwise nucleotide differences. However, the mitochondrial gene pool of Altaian Germans also differed from that of Western European populations. The gene pool of Altaian Germans contained the ancestral variants of the main haplotypic groups. To date, these variants have not been found in modern Western and Central European populations, which is apparently due to their lower frequencies. In addition, some previously unknown mtDNA variants with specific nucleotide substitutions were found in Altaian Germans. The obtained results suggest that the modern mitochondrial gene pool of Europeans, including Germans from Germany, was largely affected by the demographic processes that occurred in the past two centuries. The Germans that lived in Russia were relatively isolated and, hence, retained more characteristics of the ancestral gene pool.     

Genetic variation of isolated and peripheral populations of Pinus sylvestris (L.) from glacial refugia

Analysis of variation at 10 polymorphic isoenzyme loci in 51 European populations of Pinus sylvestris both from its main continuous range and from isolated, marginal populations out of the continuous range, revealed differences in genetic structure. The highest genetic richness, measured as mean number of alleles per locus, was recorded for populations from the Iberian Peninsula, followed by those from Scotland and the Balkans. Marginal, isolated populations were characterized by much greater interpopulation variation than populations from the continuous range of the species. The highest mean observed heterozygosity was recorded for the Iberian populations. The highest gene flow was observed among populations in the continuous range of the species. The populations could be classified into five groups based on genetic similarities. Populations from the continuous range formed one group, those from Spain two groups, pines from Scotland one group and those from the Balkans one group. One population from Scotland was found to be most distinct from the other Scottish pines and was found to be grouped with the Balkan populations. The occurrence and frequencies of rare alleles in the populations showed a characteristic pattern, suggesting that populations from the Iberian Peninsula probably did not participate in the colonization of Europe by Pinus sylvestris after the last glaciation. In contrast, the migration of populations from the Balkan refugium into Central and Western Europe had a significant effect on the contemporary gene pools of populations of Pinus sylvestris in its continuous range.     

Genetic screening of the G2019S mutation of the LRRK2 gene in Southwest European, North African, and Sephardic Jewish subjects

The G2019S mutation in exon 41 of the leucine-rich repeat kinase 2 (LRRK2) gene accounts for 3-6% of familial dominant Parkinson's disease (PD) and for 1-2% of sporadic PD. It seems that there is a north-south gradient of G2019S frequency in Europe in PD patients, and the frequency of the mutation is up to 41% in North African cases. To obtain a precise estimate of G2019S frequency in populations with relatively elevated incidence of mutation carriers, we have tested for the presence of the G2019S in the south Mediterranean countries. Three thousand one hundred healthy European subjects were compared for the G2019S incidence with 597 healthy Arab subjects originating from five populations in North Africa and with 361 healthy Sephardi Jews from five other populations. The main incidence of G2019S carriers is 1/46 in our sample of North African Arabs, the most elevated carrier incidence (1/30) being found in Moroccan Berbers. An elevated incidence (1/72) is also found in our sample of Sephardi Jews. These results contrast with the ones we found (1/1550) in a sample of 3100 healthy subjects originating from 15 populations of southern Europe. Six microsatellite markers were used in the 20 G2019S carriers we found, to conduct a haplotype analysis. Our finding on the elevated incidence of the G2019S mutation in North African Arabs and in Sephardi Jews, Berbers being the people where the mutation probably originates from, has some important consequences for future genetic diagnosis and counseling for PD in these populations.     

A map of copy number variations in Chinese populations

It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ～35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%), which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a useful resource in further evolutionary and medical studies.     

High genetic similarity between Polish and North European Scots pine (Pinus sylvestris L.) populations at nuclear gene loci

Nucleotide polymorphisms in a set of 32 nuclear genes were studied in 19 mountain, peatbog and lowland populations of Scots pine representing known phenotypic races and populations of presumably relict character for the species in Poland. At 29 genes, the pattern of genetic variation was compared to 11 reference populations from Northern, Western and Southern Europe. Similar levels of nucleotide polymorphism and excess of low-frequency mutations were observed in Polish populations (π _tot?=?0.0055, D?=??0.308) and as compared to the reference samples (π _tot?=?0.0054, D?=??0.170). Bayesian assignment and conventional frequency-based statistics indicate that Polish populations share the same genetic background at the analysed nuclear gene markers. However, the populations showed a much closer genetic relationship with North European samples than other regional groups of populations. Across the very uniform genetic background of the populations, we identified several genes with outlier patterns of haplotype, polymorphism frequency variation and departures from compound neutrality tests. Our data indicate that the Central and North European parts of the Scots pine distribution seem particularly suitable for association genetic studies to link phenotypic and genetic variation at a large geographical scale.     

High frequency of CYP1A1*2C allele in Brazilian populations

The genetic variability of the CYP1A1 I462V polymorphism (CYP1A1*2C) was investigated in four Brazilian populations: three groups of African descent and one group of European descent. The CYP1A1 polymorphism was analyzed by two different procedures, first by the allele-specific polymerase chain reaction (PCR) method and then by the PCR-restricted fragment length polymorphism (PCR-RFLP) method before digestion with BsrDI. The frequency of CYP1A1 *2C was 11% in Brazilians of European descent, a frequency that is slightly higher but not statistically different from that observed in European populations. In Brazilians of African ancestry this value was very high (12% to 15%). This allele was not observed in the only two African populations investigated thus far. By themselves, the two factors of interethnic admixture (with populations of European descent and/or Amerindian populations) and genetic drift cannot explain the high values observed here. Our findings suggest that the CYP1A1 *2C allele may possibly be present in Africa, but restricted to some ethnic groups not yet investigated. Environmental factors in South America might also have acted as selective factors increasing the CYP1A1 *2C gene frequency. Our data also suggest that the CYP1A1 *2C allele might possibly have originated in Africa.     

Comparison between mitochondrial and chloroplast DNA variation in the native range of Silene vulgaris

A detailed survey of mitochondrial and chloroplast diversity in eight populations of Silene vulgaris from Central Europe was conducted for comparison with previously published data on diversity from S. vulgaris populations in the introduced range. Mitochondrial DNA (mtDNA) variation around the coxI gene was assessed with Southern blotting/restriction fragment length polymorphism methods. Chloroplast variation was assessed by sequencing the intergenic spacer separating the trnH and psbA genes. Thirty mtDNA haplotypes and 24 chloroplast DNA (cpDNA) haplotypes were found within 86 individuals. The overall genetic diversity h (0.941 for mitochondrial, and 0.893 for chloroplast markers) and within-population diversity were higher than reported in previous population studies of S. vulgaris in the USA and Europe. The frequency of private alleles was surprisingly high - more than 90% for both kinds of markers. Most of our populations were large and located in relatively undisturbed meadows, whereas surveys in Virginia consisted of smaller roadside populations. The slow rate of population turnover in European populations is discussed as a factor responsible for the relatively high diversity of S. vulgaris in undisturbed areas of its native range. Association between mtDNA and cpDNA haplotypes was also demonstrated. Finally, gender and mtDNA haplotype were associated in the Alps populations, where females were very rare.     

α1 (Pi) types and subtypes in the Tyrolean population

Since nine patients with infantile liver cirrhosis or hepatopathy associated with the Pi ZZ phenotype had been observed in recent years in the Children's Hospital of the University of Innsbruck, Tyrol, the distribution of the Pi types and the PiM subtypes was determined in the Tyrolean population. Apparently healthy blood donors (868) from different regions of Tyrol were examined. Isoelectricfocusing was used for classification of Pi types. The frequency of the allele PiZ was 0.0138, which corresponded to the range observed in other Middle European populations. The frequencies for the suballeles of PiM were PiM1 = 0.7062, PiM2 = 0.1480, and PiM3 = 0.1037. PiS had a frequency of 0.0225, the other rare alleles occurred with a combined frequency of 0.0058.     

宁夏回族红细胞血型的研究

调查了219名宁夏回族的 ABO、MNSs、Rhesus、P、Lewis、Duffr、Kidd Diego 、Kell、Lutheran和Xg等11种系统的红细胞血型。结果表明,宁夏回族有较高的q(0.2530)、Fy~a(0.9270)、CDe(0.6225) 和E(0.2660) 等基因或染色体频率;d(0.0557)、s(0.0594)、P_1(0.1316)和 Le~a(0.3882)等基因频率较低;而未发现K和Lu~a基因;Di~a的频率为0.0349,也处于低水平;Ns(0.4984)连锁率高于 Ms(0.4422);Xg~a基因频率为0.4432。11个系统的红细胞血型的分布和遗传距离分析均反映了宁夏回族的遗传组成具有我国北方民族的特征,尤其接近于北方汉族和蒙古族,与新疆维吾尔族则存在较大的差异。     

Evolutionary and biogeographical patterns within Iberian populations of the genus Squalius inferred from molecular data

Origins and biogeography of the chub, genus Squalius (formerly within the genus Leuciscus), in the Iberian Peninsula were inferred from comparison between patterns of geographic distribution and phylogenetic relationships among populations belonging to 14 European Squalius species. The phylogeny recovered was based on the complete sequence of the mitochondrial cytochrome b gene. Squalius species were grouped into three major clades. The basal clade included species distributed across the ancient Paratethys Sea. The second clade included species from Central and East Europe and the northern areas of the Mediterranean basin towards Minor Asia. The third clade included species from the Mediterranean Peninsulas (Iberian, Italy, and Balkans). The Iberian Squalius species do not constitutes a monophyletic group. Our data indicate that the Iberian Peninsula was colonized at least twice by two different monophyletic lineages, a meridional group and a Central Europe group. The amount of species diversity found in the Iberian Peninsula and the phylogenetic relationships among these species, together with their geographic distribution, suggest that the Central Europe lineage colonized the Iberian Peninsula at a latter time. Our data indicate that the northeastern Iberian lineage is phylogenetically close to Greek populations of Squalius cephalus, while the second lineage formed a monophyletic group including Squalius pyrenaicus, Squalius carolitertii, Squalius aradensis, and Squalius torgalensis. The speciation process that generated these species and the geographic structure of their populations, principally in S. pyrenaicus, can be attributed to paleogeographical events like the ancient endorrheism and the development of hydrographic basins.     

Analysis of four diverse population groups indicates that a subset of cystic fibrosis mutations occur in common among Caucasians.

To determine the nature and frequency of non-delta F508 cystic fibrosis (CF) mutations among diverse populations, we have sequenced exons 9-12 and 19-23 of the CF transmembrane conductance regulator (CFTR) gene from 128 CF chromosomes (39 U.S. Caucasian, 27 African-American, 42 Northern Irish, and 20 Israeli chromosomes). These regions were chosen because they encode the two putative ATP-binding folds of CFTR, domains which appear to have functional significance. In addition, CFTR exons 1 and 2 were analyzed in the American patients. Mutations were found on 49 of the 128 CF chromosomes. Nineteen different mutations were observed; six were novel, while the remaining 13 had been reported previously by our group or by other investigators. Six of nine different mutations found in African-American patients were unique to that population. However, the vast majority of the mutations found in U.S. Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians. A survey of mutation frequencies in other Caucasian groups confirmed this observation. Unfortunately, this subset accounts for less than half of non-delta F508 CF mutations in most groups. These data suggest that screening for delta F508 and this select group of mutations will efficiently and economically maximize the number of CF mutations identified in Caucasian groups. However, it will be difficult to detect more than 90% of mutant CFTR alleles except in ethnically and geographically discrete populations where CF is the result of founder effect.     

Genetic Diversity of Magnaporthe grisea in China as Revealed by DNA Fingerprint Haplotypes and Pathotypes

We determined DNA fingerprint haplotypes and pathotypes of the rice‐blast fungus Magnaporthe grisea collected from 13 areas in China. This DNA fingerprinting analysis, using rep‐PCR, of 381 haplotypes (482 isolates) from China indicated that the M. grisea populations cannot be delineated into region‐specific groups. Analyses of the number of alleles (na), Nei's gene diversity, unbiased genetic distance, and Shannon's Information index among 13 populations showed that clusters were not related to the geographic distance between populations with the exception of the Ningxia (NX) and Jilin (JL) cluster. Among northern populations, NX and JL were more similar to one another than to other populations. Pathogen populations consisting of 121 isolates from China were grouped into 53 pathotypes on the basis of disease reaction in differential rice lines. Isolates assayed for pathotypes were detected based on disease reactions. No correlation was observed between fingerprint groups and pathotypes of the pathogen. High frequency of virulence was found on the rice line Shin2 (Pi‐k^s and Pi‐sh) followed by PiNo.4 (Pi‐ta² and Pi‐sh) and K1 (Pi‐ta), while it was low on Kanto 51 (Pi‐k + ?), K3 (Pi‐k^h), and Fujisaka (Pi‐i and Pi‐sh). Virulence was rare on Toride 1 (Pi‐z^t and Pi‐sh). Tetep (Pi‐k^h + ?) was predicted to be a highly effective, as none of the isolates infected this line. These blast‐resistant rice lines can be used in resistance breeding for the effective management of rice blast in the respective regions of China.     

Lewis phenotypes and secretor character in the "Castilla la Nueva"-region (Spain). ABH and Lewis antigen levels in salivary secretion

In 1980 blood and saliva samples were taken from Spanish students of the University of Madrid. Red cells were analysed for A1B2BO and Lewis blood groups. Saliva samples were tested to detect the specific group substances ABH, Lea and Leb. A slightly higher frequency of the "le" gene (0.419) was found in our sample as compared to other Spanish samples. The phenotype frequencies of ABH secretors (77.2%) and non-secretors (22.8%) are in the range of other European populations. The levels of A and B antigens of individuals belonging to these blood groups were similar, whereas the average titration of the H substance showed the relation O greater than A2 greater than A1 greater than A1B greater than B. Analysis of variance proved this heterogeneity to be statistically significant. The amount of Lea substance in non-secretors was higher than in secretors. This shows again that the ABH secretor status has some influence on the quantity of this antigen. The average titration of the Leb substance in secretors was higher than that of Lea in individuals belonging to O, A and AB blood groups, but not in those with blood group B.     

Phenotype and gene distribution of alpha-1-antitrypsin in a North Italian population.

A group of 202 unrelated Italians were screened for alpha1-antitrypsin using agarose-acrylamide electrophoresis and isoelectric focusing. The S and F gene frequencies were comparable to those found among Greeks and North European populations but they differed considerably from the frequencies found among Spaniards and Portuguese. The other gene frequencies appeared to be comparable to other populations, studied.     

The development of the gene pool in the microevolution of <Emphasis Type="Italic">Sus scrofa</Emphasis> and the role of heterozygosity in the breed-forming process

The gene pool formation of the modern domestic breeds of pig Sus scrofa domestica and their genesis based on hybridization of wild ancestral forms of the European and Asian origin were studied using molecular immunogenetic methods. Males of the European and Central Asian S. scrofa subspecies (S. s. scrofa and S. s. nigripes were hybridized with domestic pigs of the Swedish Landrace and Vietnamese Black Masked breeds. In addition, we examined the genotypic structure of 65 wild, aboriginal, and local populations as well as cultured breeds, including the stock breeds with different levels of selection. Frequencies of alleles and suballelles of the chromosome 4 locus controlling antigens of the L blood group system were analyzed. The origin of marker suballeles of the European and Asian origin was estimated in the most widespread world pig breeds. Unexpectedly, a strikingly high frequency of the Asian elements was found in the most productive European and American breeds, as well as in the best breeds of Russia and other CIS countries. Only one form of heterozygosity (bcgi/bdfi) was found in a population of wild European ancestors, whereas domestic pig breeds displayed heterozygosity for far more numerous suballeles of the locus studied. Animals with heterozygosity for alleles of the European and Asian origin showed higher adaptivity and fertility.__________Translated from Genetika, Vol. 41, No. 4, 2005, pp. 566–576.Original Russian Text Copyright © 2005 by Tikhonov.     

Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study

A cross-sectional study on intestinal microbiota composition was performed on 230 healthy subjects at four European locations in France, Germany, Italy, and Sweden. The study participants were assigned to two age groups: 20 to 50 years (mean age, 35 years; n = 85) and >60 years (mean age, 75 years; n = 145). A set of 14 group- and species-specific 16S rRNA-targeted oligonucleotide probes was applied to the analysis of fecal samples by fluorescence in situ hybridization coupled with flow cytometry. Marked country-age interactions were observed for the German and Italian study groups. These interactions were inverse for the predominant bacterial groups Eubacterium rectale-Clostridium coccoides and Bacteroides-Prevotella. Differences between European populations were observed for the Bifidobacterium group only. Proportions of bifidobacteria were two- to threefold higher in the Italian study population than in any other study group, and this effect was independent of age. Higher proportions of enterobacteria were found in all elderly volunteers independent of the location. Gender effects were observed for the Bacteroides-Prevotella group, with higher levels in males than in females. In summary, age-related differences in the microbiota makeup were detected but differed between the study populations from the four countries, each showing a characteristic colonization pattern.     

Parental Analysis of Introgressive Hybridization between African and European Honeybees Using Nuclear DNA Rflps

African honeybees, introduced into Brazil 33 years ago, have spread through most of South and Central America and have largely replaced the extant European bees. Due to a paucity of genetic markers, genetic interactions between European and African bees are not well understood. Three restriction fragment length polymorphisms (RFLPs), detected with random, nuclear DNA probes, are described. The polymorphisms are specific to bees of European descent, possibly specific to certain European races. Each European marker was found present at a high frequency in U.S. colonies but absent in South African bees. Previous mitochondrial DNA studies of neotropical bees have revealed negligible maternal gene flow from managed European apiaries into feral African populations. The findings reported here with nuclear DNA show paternal gene flow between the two but suggest asymmetries in levels of introgressive hybridization. Managed colonies in southern Mexico, derived from European maternal lines, showed diminished levels of the European nuclear markers, reflecting significant hybridization with African drones. The European alleles were present only at low frequencies in feral swarms from the same area. The swarms were of African maternal descent. In Venezuelan colonies, also derived from African maternal lines, the European markers were almost totally absent. The results point to limited paternal introgression from European colonies into the African honeybee populations. These findings dispute other views regarding modes of Africanization.