Analysis of the Allele Polymorphism of (CTG)nand (CAG)n Triplet Repeats in Loci DM, DRPLA, and SCA1 in Several Populations of Russia

Polymorphism of highly polymorphic triplet repeats CTG of the 3"-untranslated region of the myotonin protein kinase gene and CAG of the genes associated with dentatorubral-pallidoluysian atrophy (DRPLA, or Hew River syndrome) and spinocerebellar ataxia type 1 (SCA1) was analyzed in several ethnic populations of Russia. A difference in allele spectra of the three genes was demonstrated for populations differing in ethnic origin.     

The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe

The STR (AAAAT)n within intron 1 of the TP53 locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans, and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126/7 (bp/copies of the repeat), 131/8 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R(ST)) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within Europeans.     

Polymorphism of glutathione S-transferases M1 and T1 in several populations of Russia

Frequencies of the wild-type and null genotypes of the GSTM1 and GSTT1 genes were established in healthy donors from several Russian populations (ethnic Russians from the towns of Oshevensk and Kholmogory, Arkhangel'sk oblast; ethnic Khants; ethnic Kalmyks; and ethnic Buryats) in order to identify the ethnic group with the maximal frequency of the null genotype. The highest frequency of individuals with the null genotype of both genes was observed in the Kalmyk and Buryat populations. The results may be used to study the effect of climatic and ecological conditions on multifactorial disease incidence in populations.     

Polymorphism of Glutathione S-Transferases M1 and T1 in Several Populations of Russia

Frequencies of the wild-type and null genotypes of the GSTM1 and GSTT1 genes were established in healthy donors from several Russian populations (ethnic Russians from the towns of Oshevensk and Kholmogory, Arkhangel'sk oblast; ethnic Khants; ethnic Kalmyks; and ethnic Buryats) in order to identify the ethnic group with the maximal frequency of the null genotype. The highest frequency of individuals with the null genotype of both genes was observed in the Kalmyk and Buryat populations. The results may be used to study the effect of climatic and ecological conditions on multifactorial disease incidence in populations.     

Polymorphism of the (CTG)n Repeat of the Myotonin Protein Kinase Gene in Populations of the Sakha Republic (Yakutia) and Central Asia

The allele frequency distribution of the (CTG)_n repeat located in the 3′-terminal region of the myotonin protein kinase gene (DMPK) was compared for populations of Yakutia (three ethnogeographic groups of Yakuts, Evenks, Evens, Yukaghirs, and Dolgans) and Central Asia (Kazakhs, Uzbeks, and Uighurs) and other ethnic groups. The populations of the two regions proved to considerably differ from each other: features characteristic of Asian Mongoloids were more distinct in the populations of Yakutia, while the Central Asian populations were closer to European populations. The (CTG)_n allele spectrum of Yakuts was considered in connection with the high incidence of myotonic dystrophy in Yakutia. The results support the hypothesis of the founder effect for the spread of myotonic dystrophy in Yakuts. Data on the (CTG)_n polymorphism were used to estimate the phylogenetic relationships of the populations under study.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 3, 2005, pp. 385–393.Original Russian Text Copyright © 2005 by Fedorova, Khusainova, Kutuev, Sukhomyasova, Nikolaeva, Kulichkin, Akhmetova, Salimova, Svyatova, Berezina, Platonov, Khusnutdinova.     

(AC)n dinucleotide repeat polymorphism in 5' beta-globin gene in native and Mestizo Mexican populations.

Repeated sequences are dispersed along the human genome. These sequences are useful as markers in diagnosis of inherited diseases, in forensic medicine, and in tracking the origin and evolution of human populations. The (AC)n repeated element is the most frequent in the human genome. In this paper, the (AC)n repeated element located in the 5' flanking region of the beta-globin gene was studied by single-strand conformation polymorphism (SSCP). Four ethnic Mexican groups (Mixteca, Nahua, Otomí, Purépecha) and a Mestizo population were analyzed. We observed three alleles, A [(AC)16, B [(AC)14], and C [(AC)18], with a frequency of between 68.2% and 86.9%, 13.1% and 18.2%, and 6.7% and 13.7%, respectively. Allele C was present only in Purépecha and Mestizo groups. The absence of this allele in the other ethnic groups studied suggests that there is low genetic admixture of Purépecha and that this is a relatively isolated population. However, it could be that the C allele occurs in low frequencies in the other groups as a result of small sample sizes. The (AC)n repeat polymorphism in the beta-globin gene has not been previously studied in Amerindian populations.     

Frequencies of promoter pentanucleotide (TTTTA)n of CYP11A gene in European and North African populations

The present work attempts to determine the distribution of CYP11A (TTTTA)n genotype and allele frequencies in 10 European and North African populations. This polymorphism has been associated with hyperandrogenism by several association studies. To our knowledge, this is the first study investigating the ethnic variation of this polymorphism. DNA was extracted from 868 whole-blood samples with the standard phenol-chloroform technique, and PCR reactions were carried out using fluorescent primers as described previously. PCR products were analyzed by an ABI 3,730 DNA Analyzer. A total of six alleles were identified, ranging from 220 bp (4 repeats [4R]) to 250 bp (10R). The most frequent allelic fragment size in all populations was 4R, with frequencies ranging from 47.9% (Sicily) to 62.8% (Tuscany and Germany). Allelic frequencies showed high heterogeneity between analyzed populations. We detected a significant gradient for alleles 4R and 8R. In this study, we report the allele frequency distribution of CYP11A (TTTTA)n showing a north-south geographic gradient. This result could be useful for epidemiological studies about hyperandrogenism.     

Diversity of killer cell immunoglobulin-like receptor genes in four ethnic groups in China

Killer cell immunoglobulin-like receptors (KIRs) show extensive variation in terms of gene content and allelic polymorphisms among different populations. The aim of this study was to analyze the distribution of KIR genes in the Bulang, Nu, Yugu, and Zhuang ethnic groups, which belong to four different language families in China, and thus to provide basic KIR gene and genotype data for these Chinese ethnic groups. Genotyping of 16 KIR genes was performed in 425 unrelated individuals using the polymerase chain reaction-sequence-specific oligonucleotide probe method with the Luminex MultiAnalyte Profiling System. The four framework KIR genes were detected in all four ethnic groups. The activating KIR genes as well as the inhibitory KIR genes showed extreme diversity among these four populations. A total of 35 distinct KIR genotypes were identified, one of which was previously unknown. The four most common genotypes were identified in all four populations and comprised 66.1~91.1% of all the genotypes. The group A haplotype occurred more frequently than the group B haplotype in the Nu, Yugu, and Zhuang populations, as in other East Asian populations. In contrast, the group A and group B haplotypes occurred equally in the Bulang population. The results of the present study suggested that the KIR genes and genotypes are diverse in these four ethnic groups, and each ethnic group has its own characteristic KIR distribution. The findings with respect to KIR gene diversity in these four populations should provide relevant genomic diversity data for the future study of viral infections, autoimmune diseases, and reproductive fitness.     

Ethnic variations of a retinoblastoma susceptibility gene (RB1) polymorphism in eight Asian populations

An A → G single nucleotide polymorphism (SNP) at nucleotide 153,104 in the retinoblastoma susceptibility locus (RB1) at 13q14 was previously reported to be present only in Asians. In this study, we determined the distribution of this SNP in normal Southeast Asian populations (Chinese, Malay, Javanese, Thai, Filipino), in South Asian populations (Bangladeshi, Pakistani Pushtun and Indian) and in Chinese retinoblastoma cases and control subjects. TheRB1 SNP was present in all populations at an overall frequency of ≤0.18. Heterozygosity was higher in the Southeast Asian groups (0.14–0.34) than in the South Asian groups (Bangladeshi and Indian) (0.04–0.06). Significant differences in allele frequencies were found between the two population groups. Interestingly, our Pakistani population comprised of ethnic Pushtuns from northwest Pakistan was significantly different from the neighbouring Bangladeshi and Indian populations. No significant difference was found between Chinese case patients and control subjects. ThisRB1 SNP appears to be an ethnic variant prevalent in Southeast Asian populations and may be useful for studyingRB1 inheritance by pedigree analysis.     

Study of five haemogenetic markers (Gc, C3, Bf, Ag, and GALT) in six Indonesian populations and in 12 subgroups of Balinese

In various ethnic groups of the Indonesian archipelago and of Bali, the polymorphisms of the serum proteins Gc globulin (vitamin D-binding protein), C3 (complement component 3), Bf (complement factor B), Ag x,y (lipoprotein allotypes), and of the red cell enzyme system GALT (galactose-1P-uridyltransferase) were analysed. Among the studied proteins, the Gc system was the most informative one for the anthropologist. Besides considerable differences of frequencies of the common alleles Gc*1F, Gc*1S and Gc*2, a number of rare alleles (1A1, 1A3, 1A8, 1A9, 1A12, 1C2, 1C21, 1C24, and 2C8) and some new ones (1C28, 1C29, 1C30, 2C9) were observed. The presence of Gc*1A1 demonstrates the relationship to the Australo-Melanesian populations, but Mongolian variants (1A3, 1A8, 1A9, 1C2) were also encountered. Within the C3 system a very high frequency of the C3*S allele was observed in all populations. The rare alleles C3*F0.55, C3S1, and C3*S0.5 were observed in some groups. A new allele (C3*F0.35) was detected in a Chinese individual and in a nobleman from Bali. The frequency of the Bf*F allele was rather low in general, and the Bf*S0.7 allele was found in three Indonesian individuals only. The Ag*(x) frequencies were rather high, as it is known for Asiatic populations. Variability among subgroups was not very pronounced. The GALT*2 allele (Duarte variant of the enzyme) was observed very rarely; however, it was present in several populations. Enzyme activities could not be determined, and therefore we cannot tell whether the galactosaemia gene (GALT*0) was present or not.     

Low variability of the POLG (CAG)n repeat in north Eurasian populations

We investigated the frequency of different repeat-length alleles of the trinucleotide CAG microsatellite repeat in the coding sequence of the nuclear gene for the catalytic subunit of mitochondrial DNA polymerase gamma (POLG) in 12 ethnic groups from northern Eurasia. The population sample consisted of 1,330 individuals from 3 large geographic areas: Europe, Southwest Asia, and Siberia/East Asia. We found that the 10-repeat allele of the POLG gene is the most frequent in all analyzed populations, with a frequency of 88-96%. The heterozygosity level ranges from 22% in Europe to 13.6% in Southwest Asia with the lowest value of 7.4% in Siberia/East Asia. The present study provides evidence of clinal distribution of POLG gene heterozygosity in North Eurasian populations. In general, we found an extremely low variability of the trinucleotide CAG microsatellite repeat, suggesting that purifying selection acts against deleterious alleles, although low mutability of the repeated region cannot be ruled out.     

Genetic variation among four Mexican populations (Huichol, Purepecha, Tarahumara, and Mestizo) revealed by two VNTRs and four STRs

Allele distributions of two polymorphisms with variable number of tandem repeats (VNTR), D1S80 and APOB, and four polymorphisms with short tandem repeats (STR), VWA, TH01, CSF1PO, and HPRTB, were analyzed in three Mexican ethnic groups: Huichol, Purepecha, and Tarahumara. Genotype distribution was in agreement with Hardy-Weinberg expectations for each locus and ethnic group. Heterozygosity (H), power of discrimination, and probability of exclusion were estimated. The three groups presented some distinctive genetic features: (1) a diminished genetic diversity (H = 66.8% to 73.4%) and mean number of alleles by locus (5.8 to 6.3) in comparison with Mexican mestizos (H = 78.3%, 10.5 alleles/locus), and (2) uneven allele distributions as evidenced by "distinctive alleles" with high frequencies, especially in the Tarahumara and the Huichol. Genetic relatedness analysis included data from a previously typed mestizo population, the largest and most widely distributed population in Mexico. Allele distribution differentiation was observed among all four groups, except between mestizo and Purepecha (p > 0.05), which was interpreted as indicating a larger Spanish component in the Purepecha as a result of gene flow effects. Although intrapopulation inbreeding (FIS) was not significant, heterozygote deficiency in the total population (FIT) and divergence among populations (FST) were significant (p < 0.05). Genetic distances displayed a closer relationship among mestizos, Purepechas, and Huichols in relation to Tarahumaras. Correlation between the observed genetic features and the geographic isolation level points to genetic drift as the main cause of differentiation among these Mexican populations.     

Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in Inhabitants of Astana,the Capital City of Kazakhstan

Background

Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations.

Methodology/Principal Findings

A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians.

Conclusions/Significance

The HLA-DRB1, -DQA1and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations.     

Alleles and haplotypes of tumor necrosis factor (TNF) alpha and beta genes in three ethnic populations of Sulawesi Indonesia

Polymorphic variation in two cytokine genes, tumor necrosis factor (TNF) -alpha and -beta, was examined in three ethnic groups, the Bugis, the Makassans, and the Torajans, who inhabit Sulawesi, a large island in the Indonesian archipelago, and formerly a Dutch colony. TNF-alpha and -beta are key molecules in immune responses to infection, and both have been implicated in the pathogenesis and clinical manifestations of parasitic diseases. Several polymorphic variants with the potential to affect cytokine levels in autoimmune diseases and parasitic and bacterial infection have been reported. Two loci in the promoter region of TNF-alpha and two sites in the first intron of TNF-beta were scored in a maximum of 150 Bugis, 168 Makassans, and 58 Torajans. Genotypes at the two TNF-alpha loci are not in Hardy-Weinberg equilibrium because of a deficit of heterozygotes (p < 0.05). However, genotypes at the TNF-beta loci exhibit Hardy-Weinberg equilibrium. A comparison of allelic and genotypic frequencies at all TNF loci across the ethnic groups reveals that the differences are significant for TNFalpha(308) (p < 0.01) and for TNFbeta(NcoI) (p < 0.05). Overall, the distribution of the alleles differs from that seen in the few Asian populations for which data are available (p < 0.05). Construction of 4-locus haplotypes showed that, in addition to the five previously reported, four novel haplotypes were present in Sulawesi. These novel haplotypes were in low frequency, and two were seen only in Bugis (haplotypes F and J) and one (haplotype K) only in Makassans. The other, haplotype D, was present in Makassans and Torajans. Preliminary sampling of other ethnic groups suggests that three of these haplotypes (D, F, and J) may be restricted to Asian or Asian-derived populations. The frequency of the common TNF haplotypes differed between Dutch and Sulawesi populations, and these data also indicated that haplotype E, which has a relatively high frequency in the Dutch (25%), may be a useful marker of Dutch/European admixture in Indonesian populations, in which it is either rare (1%) or absent. The results suggest that unique allelic combinations with potential to influence cytokine secretion are present in Sulawesi, possibly as a consequence of parasite-driven selection, and argue for more extensive investigation of haplotype distribution in parasite-endemic areas.     

Population genetics of the group specific component (Gc) and phosphoglucomutase (PGM1) studied by isoelectric focusing

For the determination of the group-specific component (Gc) and phosphoglucomutase (PGM1) phenotypes, isoelectric focusing was performed on two samples, one of Jat Sikh of northwest India, the other of northeast English. The subtype frequencies of these two systems do not differentiate the two populations sampled. Synthesis of the existing data shows distinct PGM1 and Gc subtype frequencies in various ethnic and racial groups. The anthropological implication of these subtype frequencies is discussed.     

Analysis of 5382insC (BRCA1) and 6174delT (BRCA2) mutations in 382 healthy Chilean women with a family history of breast cancer

Breast cancer is the most common malignancy among women. Chilean studies reveal that this cancer presents the third highest mortality rate. A family history of breast cancer is one of the major risk factors for the development of this disease. BRCA1 and BRCA2 are the two main hereditary breast cancer susceptibility genes, and mutations in these genes are related to inherited breast cancer. In specific populations only some mutations have been found to be associated with susceptibility. The purpose of this study was to establish the frequency of 5382insC (BRCA1) and 6174delT (BRCA2) germline mutations in 382 healthy Chilean women with at least two relatives affected with breast cancer and in probands and their relatives from 8 high risk families for breast cancer, using mismatch PCR assay. The results obtained showed that 5382insC and 6174delT mutations were not found in either of the groups studied. The ethnic origin of the contemporary Chilean population and the data reported in the literature suggest that these mutations may be absent or have a very low frequency in this population.. This genetic study is part of a breast cancer screening program that also includes annual mammography and clinical breast examination over a five-year period. Strategies to reduce morbidity and mortality associated with breast cancer lie in early detection in women with genetic risk.     

Molecular cloning of cone opsin genes and their expression in the retina of a smelt, Ayu (Plecoglossus altivelis, Teleostei)

Five cone opsin genes of landlocked ayu fish (Plecoglossus altivelis) were cloned, and the expression patterns of these genes were investigated. AYU-LWS, -RH2-1, -RH2-2, -SWS1-1, and -SWS1-2 were isolated and had high (more than 75%) identity with red, green, green, UV, and UV-sensitive opsin, respectively, genes of other fish reported previously. The results of Southern blotting experiments showed that each gene is present as a single copy. Gene expression was measured by RT-PCR using four populations collected from rivers and a lake in spring and summer. The results of the RT-PCR experiment showed that AYU-SWS1-2 was highly expressed, whereas AYU-SWS1-1 was scarce. Two RH2 opsins were expressed simultaneously in the same individual, and the expression ratio between these opsins changed among populations. In situ hybridization revealed that AYU-LWS and -RH2-1 were expressed in the double cones and that AYU-RH2-2 and -SWS1-2 were expressed in the long and short single cones (LSC and SSC), respectively. It was shown that an individual ayu expresses two RH2 opsins simultaneously in different types of cone cells.     

Length variations in the COII-tRNA(Lys) intergenic region of mitochondrial DNA in Indonesian populations.

The prevalence of a 9-base-pair (bp) deletion between the mitochondrial cytochrome oxidase II (MTCOX*2) and lysine tRNA (MTTK) genes (region V) has been used to estimate the genetic relationships among Asian and Pacific populations. Many East Asian and Pacific Island populations have been examined previously, but the mitochondrial DNA (mtDNA) diversity of the intervening Indonesian archipelago has not previously been systematically examined. The 17,500 islands of Indonesia currently contain nearly 213 million people and extensive cultural, linguistic, and, presumably, genetic diversity. This study of 1091 individuals representing 15 ethnic groups is the most extensive mtDNA survey to date of the Indonesian archipelago. Six distinct length polymorphisms in region V were observed within these 15 populations. The 9-bp deletion was found in every population examined at frequencies comparable to those of previously examined East Asian populations and substantially lower than those in most Pacific Island populations. Despite the inclusion of Austronesian-speaking populations and a Papuan-speaking population, there was no statistically significant heterogeneity in the frequency of the 9-bp deletion among the 15 populations (p = 0.09). These data indicate that substantial gene flow occurred among the populations at some time in the past. Our observations of no significant correlations between genetic and geographic distances (r = -0.04, p = 0.53) coupled with the extensive cultural and linguistic differences currently within the archipelago suggest that little gene flow among neighboring populations has occurred recently.     

Prevalences of hereditary diseases in various populations in Russia

The geographic distribution of hereditary diseases (HDs) in different populations and ethnic groups of Russia has been studied. The main patterns of the formation of the prevalence and spectrum of HDs in five ethnic groups (Russians from six regions, Mari, Chuvashes, Udmurts, and Adygeans) from a total of ten regions of Russia have been analyzed. Analysis of correlations suggests that genetic drift is the main factor of the genetic differentiation of populations with respect to the prevalence of HDs. Accumulation of HDs in individual populations and ethnic groups has been analyzed. Hereditary diseases characterized by locally high prevalence rates in individual populations or ethnic groups have been detected. The main patterns of the accumulation of individual diseases and differences between populations and ethnic groups in this respect have been studied with the use of principal component analysis, which describes these patterns more graphically. It has been demonstrated that the genes of HDs are a promising tool for characterizing ethnogenetic processes in populations.     

Single-nucleotide polymorphisms and haplotype analysis in beta-defensin genes in different ethnic populations

Beta-defensins are cationic antimicrobial peptides expressed by epithelial cells and exhibit antibacterial, antifungal, and antiviral properties. The defensins are part of the innate host defense network and may have a significant protective role in the oral cavity and other mucosa. Defects or alteration in expression of the beta-defensins may be associated with susceptibility to infection and mucosal disorders. We examined the occurrence of single-nucleotide polymorphisms (SNPs) in the human beta-defensin genes DEFB1 and DEFB2 encoding human beta-defensin-1 and -2 (hBD-1, hBD-2), respectively, in five ethnic populations and defined haplotypes in these populations. Fifteen SNPs were identified in both DEFB1 and DEFB2. Coding region SNPs were found in very low frequency in both genes. One nonsynonymous DEFB1 SNP, G1654A (Val --> Ile), and one nonsynonymous DEFB2 SNP, T2312A (Leu --> His), were identified. Seven sites in each gene exhibited statistically significant differences in frequency between ethnic groups, with the greatest variation in the promoter and in the 5'-untranslated region of DEFB1. DEFB1 displayed 10 common haplotypes, including one cosmopolitan haplotype. Eight common haplotypes were found in DEFB2, including one cosmopolitan haplotype shared among all five ethnic groups. Our results show that genotypic variability among ethnic groups will need to be addressed when performing associative genetic studies of innate defense mechanisms and susceptibility to disease.