The release mechanism of platelet-activating factor during shear-stress induced platelet aggregation

Data on polymorphism of the control region of mitochondrial DNA (mtDNA) in Eastern Slavs were analyzed by the median network method. A bimodal distribution of pairwise nucleotide differences between types of the mtDNA control region was revealed; distribution was similar to that found in southern European populations. The nucleotide diversity of mtDNA types in Eastern Slavs corresponded to an evolutionary age of 10-40 thousand years. Characteristics of the mitochondrial portrait of Eastern Slavs are discussed in terms of formation of the European population in Neolith.     

Phylogeography of Bufo marinus from its natural and introduced ranges

The marine toad, Bufo marinus, has a broad natural distribution extending from the south-west of the USA to southern Peru and the central Amazon. It was introduced to several localities in the Caribbean and Pacific Oceans to control sugar cane pests. We sequenced 468 bp of mitochondrial DNA (mtDNA) containing the ND3 gene, and flanking tRNA genes from toads spanning the broad natural and introduced ranges. Consistent with the known history of introductions and expected effects of serial bottlenecks, mtDNA within introduced populations in Hawaii and Australia was uniform and most closely related to samples from eastern Venezuela and French Guiana. However, mtDNA nucleotide diversity in the geographic region spanning the source areas is also relative low (0.18-0.46%) and the absence of variation in the introduced populations precludes quantitative assessment of the reduction in genetic diversity. Unexpectedly, there was a large phylogeographic break (5.4% sequence divergence) within the natural range separating populations east and west of the Venezuelan Andes. We hypothesize that the two major lineages of B. marinus were isolated by the uplift of the eastern Andean cordillera which was completed approximately 2.7 Ma. Another species of the marinus group, B. paracnemis, had mtDNA paraphyletic, with marinus, being nested within the eastern lineage. Thus, at least one speciation event within the marinus group postdates the split within marinus. These findings suggest that the taxonomy of B. marinus should be re-evaluated and that the search for pathogens to control Australian populations should be conducted in populations from both lineages in the natural range.     

Mitochondrial DNA diversity in the Kuna Amerinds of Panamá

Mitochondrial DNA (mtDNA) haplotype diversity was determined for 63 Chibcha-speaking Kuna Amerinds sampled widely across their geographic range in eastern Panamá. The Kuna data were compared with mtDNA control region I sequences from two neighboring Chibchan groups, the Ng?bé and the Huetar; two Amerind groups located at the northern and southern extremes of Amerind distribution, the Nuu-Chah-Nulth of the Pacific Northwest and the Chilean Mapuche; and with a single Na-Dene group, the Haida of the Pacific Northwest. The Kuna exhibited low levels of mitochondrial diversity as had been reported for the other two Chibchan groups and, furthermore, carried only two of the four Amerind founding lineages first reported by Schurr and coworkers (Am. J. Hum. Genet. 1990; 46: 613-623). We posit that speakers of modern Chibchan languages (henceforth referred to as the Chibcha) passed through a population bottleneck caused either by ethnogenesis from a small founding population and/or subsequent European conquest and colonization. Using the approach of Harpending et al. (Curr. Anthropol. 1993; 34: 483-496), we estimated a Chibchan population bottleneck and subsequent expansion approximately 10,000 years before present, a date consistent with a bottleneck at the time of Chibchan ethnogenesis. The low mtDNA diversity of Kuna Amerinds, as opposed to the generally high levels of mtDNA variation detected in other Amerind groups, demonstrates the need for adequate sampling of cultural or racial groups when attempting to genetically characterize human populations.     

Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 750 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of the most common mutation (DF508) in Brazilian patients of European origin is 47%. To determine the frequency of 4 other common CF mutations (G542X, G551D, R553X, and N1303K) in Brazilian patients of European origin, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards. The DNA came from 247 non-DF508 chromosomes from 172 Brazilian CF patients ascertained from 5 different states of Brazil. The results show that the 4 mutations account for 17% of the non-DF508 alleles and only 9% of the total number of Brazilian CF alleles. Overall, the frequency of each mutation is different from northern European and North American populations but similar to southern European populations, mainly the Italian and Spanish populations. When Brazilian patients of European origin are grouped according to state of birth, the frequencies of the mutations are significantly different between southern and southeastern states of Brazil. Therefore there are serious implication for risk assessment of DNA-based tests in heterogeneous populations such as Brazilians. Further studies are needed to identify the remaining 44% of CF mutations for the different populations and regions of Brazil.     

Trading genes along the silk road: mtDNA sequences and the origin of central Asian populations

Central Asia is a vast region at the crossroads of different habitats, cultures, and trade routes. Little is known about the genetics and the history of the population of this region. We present the analysis of mtDNA control-region sequences in samples of the Kazakh, the Uighurs, the lowland Kirghiz, and the highland Kirghiz, which we have used to address both the population history of the region and the possible selective pressures that high altitude has on mtDNA genes. Central Asian mtDNA sequences present features intermediate between European and eastern Asian sequences, in several parameters-such as the frequencies of certain nucleotides, the levels of nucleotide diversity, mean pairwise differences, and genetic distances. Several hypotheses could explain the intermediate position of central Asia between Europe and eastern Asia, but the most plausible would involve extensive levels of admixture between Europeans and eastern Asians in central Asia, possibly enhanced during the Silk Road trade and clearly after the eastern and western Eurasian human groups had diverged. Lowland and highland Kirghiz mtDNA sequences are very similar, and the analysis of molecular variance has revealed that the fraction of mitochondrial genetic variance due to altitude is not significantly different from zero. Thus, it seems unlikely that altitude has exerted a major selective pressure on mitochondrial genes in central Asian populations.     

A study of menarcheal age in India

A study of menarcheal age was carried out in southern India. A logit method of analysis was applied to status quo data on 1267 Tamil and Telugu speaking girls aged 9 to 18 years in 3 schools catering for different socio-economic groups. There appears to be no relationship of menarcheal age with dietary pattern classified simply as vegetarian and non-vegetarian. Differences in median age at menarche between schools correspond well with the socio-economic differences between them. The median age in the most advantaged school (12-86 years) is comparable with that in recent studies in southern and eastern Europe, and may perhaps be in advance of some recent north-west European samples.     

Extent of heterogeneity in mitochondrial DNA of European populations

Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence-specific oligonucleotide (SSO) probes is described for 595 individuals from six European or European-derived populations. Estimates of diversity for mtDNA types exceed 0.91 in all populations, while 50% of the 158 types which were observed occur only once. Of 68 shared types, most occur rarely (< 3% of the total population); only one type occurs at a frequency greater than 10%, and it is present at comparable frequencies in all six populations (18-29%). An analysis of molecular variance (AMOVA) incorporating genetic distances between types shows that 100% of the variation present in the total sample is attributable to within-population diversity, while there are essentially no between-population differences. Another AMOVA was performed for the first hypervariable region SSO sites only, which included this sample plus an additional 537 SSO types from mine more European populations that were inferred from published mtDNA control region sequence data. Similar results were obtained, with over 99% of the variation overall attributable to within-population differences, and less than 1% of the variation attributable to between-population differences. The Saami were the most different from other populations, which had been observed in an earlier study of nucleotide sequence data. Overall, there is no statistically significant heterogeneity for European populations (p > 0.001), and these groups are virtually indistinguishable with respect to mtDNA SSO types. These results demonstrate the utility of mtDNA typing for forensic investigations.     

Genetic differentiation between parapatric 'nearshore' and 'offshore' populations of the bottlenose dolphin

The existence of nearshore and offshore populations of the bottlenose dolphin has been documented throughout its range. In several cases the two regional forms have been shown to be morphologically distinct, although there is considerable overlap for most characters. The populations off the eastern coast of North America have been the subject of a long-term programme of research on their distribution and movements. In this study, we compare mitochondrial and nuclear genetic markers between dolphins classified as either nearshore or offshore type. These putative populations were found to be distinct at both nuclear and mitochondrial genetic markers. Further, the level of variation among the nearshore dolphins was reduced compared with the offshore population. A broader geographical comparison suggests a shared lineage between offshore dolphins from the western North Atlantic and both offshore and nearshore dolphins from the eastern Atlantic. These results are consistent with local differentiation based on habitat or resource specialization in the western North Atlantic, and suggest differences in the character of the nearshore/offshore distinction in different parts of the world.     

Seventy-five nuclear DNA polymorphisms in an Italian sample: a comparative worldwide study

A well defined Italian sample from Trino Vercellese (Northern Italy) is analysed for 75 nuclear DNA RFLPs. It represents the only European sample [Matullo et al 1994] which is unmixed in a comparative study of eight populations from four continents [Bowcock et al 1991a; Lin et al 1994]. Genetic substructure of this sample has been investigated by allele sharing distances and no bias or higher homogeneity is shown. Genetic variability between populations was measured by the FST statistics (average FST was 0.138 +/- 0.086). Average heterozygosity for eight populations was 0.312 +/- 0.069. Genetic distances were evaluated between pairs of populations. Phylogenetic trees were reconstructed and principal component analysis performed. Particular attention has been given to the genetic relationship between our sample and the mixed-Caucasoid sample: 14 out of 75 markers show statistically significant frequency differences (P < 0.05), 5 of which are significant at a probability level < 1%: GH/Bg1II (Lower system), D7S1/HindIII, D17S71/MspI, EPB3/PstI, HLA-DQA. Hypotheses on admixed origin of Europeans has been discussed.     

The genetic relationship between the Finns and the Finnish Saami (Lapps): analysis of nuclear DNA and mtDNA

The genetic relationships between two Finno-Ugric-speaking populations, the Finns and the Finnish Saami (Lapps), were studied by using PCR for six nuclear-DNA marker loci, mitochondrial restriction-site polymorphism, and sequence variation of a 360-bp segment of the mitochondrial control region. The allele frequencies of each of the nuclear-DNA marker loci and the frequencies of mtDNA restriction haplotypes were significantly different between the populations. The Saami showed exceptionally low variation in their mtDNA restriction sites. The 9-bp deletion common in East Asian populations was not observed, nor did the haplotype data fit into the haplogroup categorization of Torroni et al. The average number of nucleotide substitutions from the mtDNA haplotype data indicated that the Finnish Saami may be closer to the Finns than to the other reference populations, whereas nuclear DNA suggested that the Finns are more closely related to the European reference populations than to the Finnish Saami. The similarity of the Finns to the other Europeans was even more pronounced according to the sequence data. We were unable to distinguish between the Finns and either the Swiss or Sardinian reference populations, whereas the Finnish Saami clearly stood apart. The Finnish Saami are distinct from other Circumarctic populations, although two of the lineages found among the Saami showed closer relationship to the Circumarctic than to the European lineages. The sequence data indicated an exceptionally high divergence for the Saami mtDNA control lineages. The distribution of the pairwise nucleotide differences in the Saami suggested that this population has not experienced an expansion similar to what was indicated for the Finns and the reference populations.     

Field trial to evaluate the immunogenicity of pseudorabies virus vaccines with deletions for glycoproteins G and E

This study is a geographically systematic genetic survey of the easternmost subspecies of chimpanzee, Pan troglodytes schweinfurthii. DNA was noninvasively collected in the form of shed hair from chimpanzees of known origin in Uganda, Rwanda, Tanzania, and Za?re. Two hundred sixty-two DNA sequences from hypervariable region 1 of which of the mitochondrial control region were generated. Eastern chimpanzees display levels of mitochondrial genetic variation which are low and which are similar to levels observed in humans (Homo sapiens). Also like humans, between 80% and 90% of the genetic variability within the eastern chimpanzees is apportioned within populations. Spatial autocorrelation analysis shows that genetic similarity between eastern chimpanzees decreases clinically with distance, in a pattern remarkably similar to one seen for humans separated by equivalent geographic distances. Eastern chimpanzee mismatch distributions (frequency distributions of pairwise genetic differences between individuals) are similar in shape to those for humans, implying similar population histories of recent demographic expansion. The overall pattern of genetic variability in eastern chimpanzees is consistent with the hypothesis that the subject has responded demographically to paleoclimatically driven changes in the distribution of eastern African forests during the recent Pleistocene.     

Mitochondrial DNA variation in Koryaks and Itel'men: population replacement in the Okhotsk Sea-Bering Sea region during the Neolithic

In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202 individuals representing one Itel'men and three Koryak populations from different parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution restriction (RFLP) analysis and control region (CR) sequencing, and the resulting data were combined with those available for other Siberian and east Asian populations and subjected to statistical and phylogenetic analysis. Together, the Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D) of the four major haplotype groups (haplogroups) observed in Siberian and Native American populations (A-D). In addition, they exhibited mtDNAs belonging to haplogroups G, Y, and Z, which were formerly called "Other" mtDNAs. While Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were widely distributed in eastern Siberian and adjacent east Asian populations, the distribution of haplogroup Y was restricted within a relatively small area and pointed to the lower Amur River-Sakhalin Island region as its place of origin. In contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs remained unclear. Furthermore, phylogenetic and statistical analyses showed that Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east Asian populations than to those of the north Pacific Rim. These results were consistent with colonization events associated with the relatively recent immigration to Kamchatka of new tribes from the Siberian mainland region, although remnants of ancient Beringian populations were still evident in the Koryak and Itel'men gene pools.     

Recombination in Tula hantavirus evolution: analysis of genetic lineages from Slovakia

To examine the evolution of Tula hantavirus (TUL), carried by the European common vole (Microtus arvalis and M. rossiaemeridionalis), we have analyzed genetic variants from Slovakia, the country where the virus is endemic. Phylogenetic analysis (PHYLIP) based on either partial (nucleotides [nt] 441 to 898) or complete N-protein-encoding sequences divided Slovakian TUL variants into two main lineages: (i) strains from eastern Slovakia, which clustered with Russian strains, and (ii) strains from western Slovakia situated closer to those from the Czech Republic. We found genetic diversity of 19% between the two groups and 4% within the western Slovakian TUL strains. Phylogenetic analysis of the 3' noncoding region (3'-NCR), however, placed the eastern Slovakian strains closer to those from western Slovakia and the Czech Republic, with a greater distance to the Russian strains, suggesting a recombinant nature of the S segment in the eastern Slovakian TUL lineage. A bootscan search of the S-segment sequences of TUL strains revealed at least two recombination points in the S sequences of eastern Slovakian TUL strains (nt 400 to 415 and around 1200) which agreed well with the pattern of amino acid substitutions in the N protein and deletions/insertions in the 3'-NCR of the S segment. These data suggest that homologous recombination events occurred in the evolution of hantaviruses.     

Molecular phylogeny of forest and field mice of the genus Apodemus (Muridae, Rodentia) based on the data on restriction analysis of total nuclear DNA

Based on restriction-fragment length polymorphism (RFLP) of total nuclear DNA (nDNA), analyses of phylogenetic relations and genetic similarity were performed in nine species of forest and field mice of the genus Apodemus. Genetic distances calculated for different species pairs ranged from 0.24 to 12.53%; i.e., the differences were 50-fold. The estimated evolutionary age of the genus Apodemus is approximately 12 million years. In general, the obtained data on genetic similarity and phylogenetic relationship allow us to differentiate at least three groups of species: (1) southern Paleoarctic (A. argenteus), (2) eastern (A. peninsulae, A. speciosus, and A. agrarius), and (3) western (A. sylvaticus, A. flavicollis, A. ponticus, A. uralensis, and A. fulvipectus) ones. The latter two groups are related to the northern Paleoarctic. Such a division into groups corresponds to characteristic features of karyotype organization and segmentation of satellite DNA (satDNA) of these species, as well as the nature of variation in isozymes and in a fragment of the enzyme-encoding sequence of cytochrome b gene isolated from the mitochondrial genome. Species groups (1) and (3) exhibited a high probability of a monophyletic origin (70 and 99%, respectively). Group (2) is unlikely to be monophyletic, and the genetic distances in it are significantly greater than those in group 3. A. argenteus is the most diverged, both phenogenetically and phylogenetically. The data are consistent with a new zoological classification, which assumes the division of the unified genus Apodemus into two taxa of generic rank and suggest that the southern Paleoarctic forest mouse should be regarded as a separate taxon of at least subgeneric rank.     

Mitochondrial DNA haplotype frequencies in natural and experimental populations of Drosophila subobscura

The evolution of Drosophila subobscura mitochondrial DNA has been studied in experimental populations, founded with flies from a natural population from Esporles (Majorca, Balearic Islands, Spain). This population, like other European ones, is characterized by the presence of two very common (>96%) mitochondrial haplotypes (called I and II) and rare and endemic haplotypes that appear at very low frequencies. There is no statistical evidence of positive Darwinian selection acting on the mitochondrial DNA variants according to Tajima's neutrality test. Two experimental populations, with one replicate each, were established with flies having a heterogeneous nuclear genetic background, which was representative of the composition of the natural population. Both populations were started with the two most frequent mitochondrial haplotypes, but at different initial frequencies. After 13 to 16 generations, haplotype II reached fixation in three cages and its frequency was 0.89 by generation 25 in the fourth cage. Random drift can be rejected as the force responsible for the observed changes in haplotype frequencies. There is not only statistical evidence of a linear trend favoring a mtDNA (haploid) fitness effect, but also of a significant nonlinear deviation that could be due to a nuclear component.     

Combination of irinotecan (CPT11) and 5-fluorouracil with an analysis of cellular determinants of drug activity

Historical population collapses caused by rinderpest epidemics are hypothesized to have resulted in notable genetic losses in populations of the African buffalo. Polymorphism in the major histocompatibity complex (MHC) DRB3 gene was probed by means of restriction analysis of the sequence encoding the peptide-binding region. Nucleotide substitution patterns agreed with a positive selection acting on this fitness-relevant locus. Buffalo populations from four National Parks, situated in eastern and southern Africa, each revealed a surprisingly high allelic diversity. Current high levels of heterozygosity may be reconciled with historical bottlenecks by assuming that local extinctions were followed by fast recolonization, in accordance with the high dispersive capabilities of buffalo. The specific amplification of DRB3 alleles also enabled the assignment of individual genotypes. For each population sample a deficiency in the expected number of heterozygous animals was found. As overdominant selection on the MHC is predicted to yield an excess of heterozygous individuals, this may not be a locus-specific effect. Several other explanations are discussed, of which increased homozygosity caused by nonrandom mating of buffalo in populations seems the most probable.     

Multiparasite communities in animals and humans: frequency, structure and pathogenic significance

A separate analysis of ulnar and radial finger ridge-counts, obtained from 115 Aymara Indians (55 males and 60 females) of northern Chile, was performed. From these variables, directional asymmetry, fluctuating asymmetry, indices of bilateral asymmetry (square root of A2), and intraindividual diversity (s/square root of 5) were calculated for each sex. The results show that most bimanual differences for the ridge-counts are not statistically significant in the Aymara, except for radial counts in female first and second fingers (right hand means are larger), while most ulnar-radial differences are highly significant in both sexes (radial values exceed ulnar ones). Most sex differences do not reach statistical significance, although males have more ridge-counts, lower directional asymmetry, somewhat lower fluctuating asymmetry, and lower indices of asymmetry and diversity than females. As fluctuating asymmetry is not larger in males, the dermatoglyphic findings do not indicate support for the hypothesis that males are less canalized than females. In accordance with the findings of other authors, interpopulation comparisons in the indices of asymmetry and diversity show ethnic differences. Both indices tend to be low in samples of African ancestry, high in samples of European origin, and intermediate in the Aymara, while Indian groups are characterized by high asymmetry and low diversity values. Moreover, the data reveal a geographical trend in that asymmetry and diversity values tend to decrease from the northern to the southern hemisphere in populations of Europe, the Middle East, and Africa, thus indicating greater ridge-count variability and heterogeneity among fingers in northern populations. It is assumed that this gradient primarily reflects different degrees of miscegenation and heterozygosity.     

Computer technology of genogeographic study of the gene pool. IV. Population in the space of principal components

On the basis of maps of principal components ("synthetic maps"), populations were arranged in the space of principal components. In terms of the applied model, nodes of a dense, uniform grid represented human populations. For each node, the frequency of a given gene was interpolated from these values for all original populations. Principal components were estimated and mapped on the basis of maps for all genes. Each population (grid node) was assigned a marker of an ethnic or some other group of populations and was positioned in the space of principal components according to the values from the original maps. The resultant "ethnic clouds" of populations and "ethnic centroids" of principal components provide some new possibilities for explaining the patterns of changes in gene pools. The maps of reliability of principal components allow the researcher to eliminate the information on populations which is unreliable and turn to the "reliable" space of principal components. The method was tested with the use of the maps of principal components for the gene pool of the East European population. Eastern Slavonic (Russians, Ukrainians, and Belarussians) and western and eastern Finno-Ugrian (Estonians and Mordovians, respectively) ethnic groups were mapped to the space of principal components. The relative positions of the populations of these ethnic groups was analyzed in the spaces of the first and the second, the first and the third, and the second and the third principal components of the East European gene pool.     

mtDNA haplotype analysis in Finnish families with leber hereditary optic neuroretinopathy

The mitochondrial DNA (mtDNA) sequence variation of 24 Finnish Leber hereditary optic neuroretinopathy (LHON) probands was characterized by sequencing and restriction endonuclease analyses. All LHON-associated substitutions and Caucasoid haplogroup-specific mutations were screened in the families. Analysis of the mtDNAs revealed that the Finnish LHON families have two unique features: an absence of the ND6/14484 mutation and a high number of families (10/24) without the primary mutations ND1/3460 and ND4/11778. Furthermore, the LHON families showed considerable mtDNA heterogeneity: among 24 families 22 haplotypes were detected. Overall, the haplogrouping of LHON families was similar to other European populations. However, the frequency of ND4/11778-positive families in haplogroup J was high, which may indicate that background mutations in this haplogroup together with the ND4/11778 primary mutation promote the penetrance of LHON.     

Estimating African American admixture proportions by use of population-specific alleles

We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.