Transferrin C subtypes and ethnic heterogeneity in Sweden

Transferrin (TF) C subtypes were studied in Swedish Lapps (Saami) and in Swedes from northern, central and southern Sweden, and the allele frequencies were compared with those in other European populations. The Swedish Lapps were found to have the lowest frequency of the TF*C3 allele (1-2%) so far observed in Europe. Most European populations have TF*C3 allele frequencies between 5 and 7%. Finns differ by having high TF*C3 frequencies (13-14%). The relatively high TF*C3 frequencies found in northeastern Sweden (13%) and in central Sweden (9%) are most likely due to eastern influence. Unlike other genetic markers of eastern influence (e.g. TF*DCHI), which are of Asiatic Mongoloid origin, TF*C3 appears to originate from Finno-Ugric populations.     

Population studies in northern Sweden. XVII. Estimates of Finnish and Saamish influence

The North-Swedish population is a mixture of Finnish, Saamish and Central-Swedish ethnic groups. We have studied the Finnish and Saamish admixture by means of genetic markers in 23 North-Swedish subpopulations. The Finnish influence was estimated using the transferrin genes B0-1, DCHI and C3 and the enzyme gene SOD1*2, and markers for Saamish influence were the blood group gene ABO*A2, the serum group gene GC*1F and the enzyme gene 6PGD*C. In the subpopulations the Finnish influence (admixture) varied between 0 and 84% and the Saamish influence between 0 and 34%. The Saamish influence was strongest in the western and northern parts of the area. In the northern part of the area, between 1/4 and 1/3 of the gene pool of the present-day population may be Saamish in origin. The Finnish influence was strongest in the northern and northeastern parts of the area. In the subpopulations along the Finnish border, between 60 and 80% of the gene pool may be Finnish in origin. Significant correlations were found between the Saamish marker genes and between the Finnish marker genes. Due to geographical overlapping of Finnish and Saamish influence, significant correlations were also found between Finnish and Saamish marker genes. The geographical pictures of Saamish and Finnish influence in northern Sweden showed a fair agreement with the expectations derived from historical knowledge. Although a substantial part of the genetic heterogeneity of the North-Swedish population is ethnic in origin, it is obvious that founder effect and genetic drift also have played an important role.     

Subtypes of transferrin C.

Subtypes of transferrin C were studied by means of isoelectric focusing after complete desialylation of transferrin. Family data were consistent with an autosomal co-dominant mode of inheritance. Studies of serum samples from 75 individuals heterozygous for C and another (B or D) variant showed that the genes (C1 and C2) controlling the C subtypes are allelic to the B and D genes. The C2 gene frequency in Swedes and Swedish Lapps was similar to that found previously in Danes and Germans.     

Studies of Transferrin Polymorphism in Swedish Cattle Using Agarose Gel Electrophoresis

The polymorphic transferrin picture in the sera from 894 Swedish cattle was investigated with an agarose gel electrophoresis technique. The serum transferrin bands in the electrophoresis pattern were first identified by labelling with 59Fe. Six existing phenotypes based on the alleles TfA, TfD and TfE could be detected. The frequencies of transferrin types and transferrin alleles are presented, and it is concluded that there are great differences in the frequencies between the Swedish Red and White and the Swedish Friesian.     

Distribution of transferrin subtypes in Tarragona (east Spain).

The distribution of transferrin (TF) subtypes was determined by isoelectric focusing of sera from 284 unrelated individuals from Tarragona (south of Catalonia). The allele frequencies observed, TF*C1 = 0.805, TF*C2 = 0.162, TF*C3 = 0.026 and TF*B = 0.007 were similar to those reported for other Spanish populations.     

Structure of allozyme variation in Nordic Silene nutans (Caryophyllaceae): population size, geographical position and immigration history

We investigated allozyme variation in 34 populations of the perennial herb Silene nutans from Sweden and northern Finland, areas that were ice-covered during the last (Weichselian) glaciation. The present geographical structure of genetic variation in S. nutans in Sweden and northern Finland appears to have been mainly shaped by ancient historical processes. Patterns of variation in allele frequencies suggest two major postglacial immigration routes into Sweden, with populations entering the area from both the south and the east and forming a contact zone with admixed populations in central Sweden. While estimates of within-population genetic diversity and allelic richness are significantly correlated with present population size and geographical position (latitude), population size is not correlated with latitude. Low genetic diversity in the northern populations is more likely to have resulted from ancient stochastic events during the process of immigration than from recent population fragmentation. F _IS values are high and increase with latitude. Evidence of recent bottlenecks was detected in several southern Swedish populations: these can be interpreted in terms of population fragmentation as a result of anthropogenic disturbance. Soil pH is uncorrelated with population size and position.  © 2004 The Linnean Society of London, Biological Journal of the Linnean Society, 2004, 81 , 357–371.     

Geographic structure of genetic variation in the widespread woodland grass Milium effusum L. A comparison between two regions with contrasting history and geomorphology.

Allozyme variation in the forest grass Milium effusum L. was studied in 21-23 populations within each of two equally sized densely sampled areas in northern and southern Sweden. In addition, 25 populations from other parts of Eurasia were studied for comparison. The structure of variation was analysed with both diversity statistics and measures based on allelic richness at a standardised sample size. The species was found to be highly variable, but no clear geographic patterns in the distribution of alleles or in overall genetic differentiation were found, either within the two regions or within the whole sample. Thus, no inferences about the direction of postglacial migration could be made. Obviously, migration and gene flow must have taken place in a manner capable of randomising the distribution of alleles. However, there were clear differences in levels and structuring of the variation between the two regions. Levels of variation, both in terms of genetic diversity and allelic richness, were lower in northern Sweden as compared with southern Sweden. In contrast, different measures of geographic structure all showed higher levels of population differentiation in the northern region. This is interpreted as due to different geomorphological conditions in the two regions, creating a relatively continuous habitat and gene flow in the southern region as compared with the northern region where the species, although common, is confined to narrow and mutually isolated corridors in the landscape.     

Modelling soil C sequestration in spruce forest ecosystems along a Swedish transect based on current conditions

The change of current pools of soil C in Norway spruce ecosystems in Sweden were studied using a process-based model (CoupModel). Simulations were conducted for four sites representing different regions covering most of the forested area in Sweden and representing annual mean temperatures from 0.7°C to 7.1°C. The development of both tree layer and field layer (understory) was simulated during a 100-year period using data on standing stock volumes from the Swedish Forest Inventory to calibrate tree growth using different assumptions regarding N supply to the plants. The model successfully described the general patterns of forest stand dynamics along the Swedish climatic transect, with decreasing tree growth rates and increasing field layer biomass from south to north. However, the current tree growth pattern for the northern parts of Sweden could not be explained without organic N uptake and/or enhanced mineralisation rates compared to the southern parts. Depending on the assumption made regarding N supply to the tree, different soil C sequestration rates were obtained. The approach to supply trees with both mineralised N and organic N, keeping the soil C:N ratio constant during the simulation period was found to be the most realistic alternative. With this approach the soils in the northern region of Sweden lost 5 g C m⁻² year⁻¹, the soils in the central region lost 2 g C m⁻² year⁻¹, and the soils in the two southern regions sequestered 9 and 23 g C m⁻² year⁻¹, respectively. In addition to climatic effects, the feedback between C and N turnover plays an important role that needs to be more clearly understood to improve estimates of C sequestration in boreal forest ecosystems.     

Gc subtypes in Finns, Swedes and Swedish Lapps

The group-specific component (Gc) subtypes were determined by isoelectric focusing and immunoblotting. The gene frequencies in the Swedish Lapps were Gc1F = 0.412, Gc1S = 0.367 and Gc2 = 0.221, which was significantly different from the frequencies found in Finns and in the populations of northern and central Sweden (p less than 0.001). The gene frequencies in the Swedish Lapps, although similar to those in Asiatic populations, are probably not reflecting an Asiatic influence, since the accumulated genetic information on the Swedish Lapps suggests that founder effect and genetic drift are to a large extent responsible for the peculiar gene pool of the original Lapp population.     

Serum protein polymorphisms in a Liberian population

Serum protein variations were studied in a Liberian population living in Buchanan town. Of the alpha 1-antitrypsin genes only M1 and M3 were polymorphic. The frequencies of the haptoglobin and Gc genes were in accordance with earlier known estimates in African populations. There was, however, a relatively low frequency of Hp 0 which may be related to the low malarial parasite prevalence in this group. The transferrin C2 gene was found in a significantly lower frequency among Liberians compared to European and Asiatic populations. A new transferrin variant was observed by isoelectric focusing. This variant could not be identified with conventional starch or polyacrylamide electrophoresis.     

Human cholinesterase genes localized by hybridization to chromosomes 3 and 16

Summary A cloned human cDNA for cholinesterase (ChE) was used as a probe for in situ hybridization to spread lymphocyte chromosomes to map the structural human CHE genes to distinct chromosomal regions. The recent genetic linkage assignment of the CHE1 locus of the CHE gene to chromosome 3q was confirmed and further refined to 3q21-q26, close to the genes coding for transferrin (TF) and transferrin receptor (TFRC). The CHE1 allele localizes to a 3q region that is commonly mutated and then associated with abnormal megakaryocyte proliferation in acute myelodysplastic anomalies. In view of earlier findings that ChE inhibitors induce megakaryocytopoiesis in culture, this localization may indicate that ChEs are involved in regulating the differentiation of megakaryocytes. A second site for ChEcDNA hybridization was found on chromosome 16q11-q23, demonstrating that the CHE2 locus of the cholinesterase gene, which directs the production of the common C5 variant of serum ChE, also codes for a structural subunit of the enzyme and is localized on the same chromosome with the haptoglobin (HP) gene, both genes being found on the long arm of chromosome 16. The finding of two sites for ChEcDNA hybridization suggests that the two loci coding for human ChEs may include nonidentical sequences responsible for the biochemical differences between ChE variants.     

Decrease of transferrin C2 frequency with age

In previous studies, transferrin C2 has been found to be associated with spontaneous abortion, prematurity, phototoxic eczema and rheumatoid arthritis. We have suggested that the mechanism behind these negative effects may be that transferrin C2 increases the risk for damage through hydroxyl radicals. This hypothesis predicts that the C2 frequency should decrease with age. Such an effect is demonstrated in this report. In a population from northern Sweden the C2 gene frequency was found to decrease from 0.173 in newborns to 0.099 in 70-year-old healthy individuals.     

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.     

QUASI analysis of the HIV-1 envelope sequences in the Los Alamos National Laboratory HIV sequence database: pattern and distribution of positive selection sites and their frequencies over years.

The envelope (env) protein of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in virus entry and is a central target for HIV vaccine design. Using the QUASI program, we analyzed the conserved regions of all currently available env sequences in the Los Alamos National Laboratory HIV Sequence Database and identified positive selection (PS) sites that are likely to be restricted by host immune responses. We found that PS sites are dispersed across conserved regions of env sequence, and that the C3, C4, and C5 regions were the most targeted. Several regions were identified as being PS free and were mainly distributed in the C1 and C2 regions. When comparing individual QUASI PS site frequencies across clades and geographical regions with the overall frequency of the entire env database, the env sequences from North America showed significantly lower PS site frequency, while those from Asia were significantly higher using Student's t test. The QUASI PS site frequency of env proteins from viruses isolated from different years showed that the PS site frequencies of the env population increased over time. Our study provides an overview of PS sites across the conserved regions of HIV-1 env sequences.     

Genetic transferrin types and iron-binding: a comparative study of a European and an African population sample

Summary Two population samples, one from Europe and one from Africa, were analyzed for the distribution of genetic transferrin (TF) types, serum concentrations of TF, serum iron concentrations and free iron-binding capacities. In Europeans the distribution of the TF alleles was C1=0.816, C2=0.143, C3=0.037 and B₂=0.004. In black Africans the allele frequencies were: C1, 0.823; C2, 0.104; and D₁=0.073; TF^*C3 was absent. The mean serum concentrations were 362±88 mg/dl in Europeans and 528±176 mg/dl in Africans; this difference was statistically significant. The concentration of serum imunoglobulins was also elevated in black Africans although their health was reported to be normal. The serum iron concentrations in Africans were decreased; the free ironbinding capacity of TF was, thus, increased; the free ironbinding capacity of TF was, thus, increased. In both population samples there was a tendency for slightly higher TF concentrations in the TF C1 subtype than the TF C2 subtype. This correlation was not statistically significant. Analysis of a larger sample is required to establish this relationship.     

Mapping of aminoacylase-1 and beta-galactosidase-A to homologous regions of human chromosome 3 and mouse chromosome 9 suggests location of additional genes.

Conserved linkage groups have been found on the X and autosomal chromosomes in several mammalian species. The identification of conserved chromosomal regions has potential for predicting gene location in mammals, particularly in humans. The genes for human aminoacylase-1 (ACY1, N-acylamino acid aminohydrolase, E.C.3.5.1.14), an enzyme in amino acid metabolism, and beta-galactosidase-A (GLB1, E.C.3.2.1.23), deficient in GM1-gangliosidosis, have been assigned to human chromosome 3. Using human-mouse somatic cell hybrids segregating translocations of human chromosome 3, expression of both ACY1 and GLB1 correlated with the presence of the p21 leads to q21 region of chromosome 3. In a previous study, assignment of these genes to mouse chromosome 9 used mouse-Chinese hamster somatic cell hybrids, eliminating mouse chromosomes. To approximate the size of the conserved region in the mouse, experiments were performed with recombinant inbred mouse strains. An electrophoretic variant of ACY-1 in mouse strains was used to map the Acy-1 gene 10.7 map U from the beta-galactosidase locus. These data suggest that there is a region of homology within the p21 leads to q21 region of human chromosome 3 and a segment of mouse chromosome 9. Since the mouse transferrin gene (Trf) is closely linked to the aminoacylase and beta-galactosidase loci, we predict that the human transferrin (TF) gene is on chromosome 3.     

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.     

Genetic serum protein markers (HP,TF, GC and PI) in eight Slovakian population samples

1194 individuals from eight different regions of Slovakia have been typed for haptoglobin (HP) types and for transferrin (TF), group specific component (GC) and alpha-1-antitrypsin (PI) subtypes. Whereas the HP allele frequencies do not show a remarkable regional variability within Slovakia, this could be demonstrated concerning the TF, GC and PI allele frequencies. The reason for these distribution heterogeneities seems to be due to the incomplete panmixia of the Slovakian population by which local variations in the distribution of genetic markers could be maintained.