Human transferrin polymorphism

The application of isoelectric focussing (IEF) has revealed a large amount of heterogeneity in the human transferrin (TF) system and has enhanced its potential value in anthropological and genetic studies. The average heterozygosity has been elevated from 0.05, observed by conventional methods of electrophoresis, to 0.29 detected by IEF. So far approximately 30,000 individuals from 122 population groups have been analyzed for TF subtypes to evaluate the magnitude of genetic variation at the TF locus. Possible environmental and biological factors, which may be operating to maintain the TF polymorphism, are discussed.     

Transferrin variants in Japan and New Zealand. Report of an unusually sialyzed TF variant

The genetic polymorphism of transferrin (TF) was studied in 2,167 Japanese individuals and in 448 New Zealanders. The three TF C subtypes were identified, but TF C3 was absent from Japanese populations. In addition, three TF B and six TF D variants were observed, each of which occurred either in Japanese or in New Zealanders. Stepwise removal of N-acetyl-neuraminic acid (NANA) with neuraminidase revealed that the most cathodal variant TF DShinnanyo found in a Japanese family was characterized by having only two NANA residues.     

Study of transferrin (TF), group specific component (GC) and alpha-1-antitrypsin (PI) subtypes in the populations of Basque country (Spain)

Genetic polymorphisms of three serum proteins Transferrin (TF), Group Specific Component (GC), and Alpha-l-Antitrypsin were investigated by isoelectric focusing (IEF) in the Basque and non Basque populations from Vizcaya and Guipuzcoa, Spain. Two of the three genetic systems (TF and PI) showed conclusive genetic heterogeneity between the Basque populations of these two provinces. In addition to the past genetic drift, the present day genetic differentiation in the Basque country seems to be contributed by the unique structure of its populations.     

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.     

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.     

Genetic diversity of serum proteins in three subpopulations of the Maria Gond tribe of Madhya Pradesh, India

The phenotype and allele frequency distribution of group specific component (GC), transferrin (TF), alpha-1-antitrypsin (PI) and apolipoprotein E (APOE) was determined by isoelectric focusing of plasma samples from three subpopulations (Bison Horn Maria of the Kuakonda and Tokapal Block, and Abuj Maria of the Abujmar Hills of the Orchha block) of the Maria Gond tribe of Madhya Pradesh, India. A considerable level of allele frequency variation was observed in these subpopulations, which highlighted social and geographical isolation among them. The average heterozygosity for these IEF subtype systems was high (29-39%) and the gene diversity among these subpopulation groups was of low to moderate range (1.4%). The overall analysis showed that these polymorphisms are useful anthropological markers for micro-evolutionary and genetic structure studies.     

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.     

Population genetics of the vitamin D binding protein (GC) subtypes in the Asian-Pacific area: Description of new alleles at the GC locus

Isoelectric focussing (IEF) in thin layer polyacrylamide gels pH range 4-6.5 has been used to analyse the GC phenotypes of 4233 individuals from 28 different population groups in the Asian, Pacific, and Australian area. Because this technique reveals subtypes of the common GC*1 allele, there is almost a two-fold increase in the mean heterozygosity at the GC locus using IEF compared with conventional electrophoresis. The highest frequency (above 50%) of the GC*1S allele was encountered in Indian populations, reflecting genetic affinities with Europeans. By comparison, east and south east Asians are unique offing maximum values of the GC*1F allele (50%). With the exception of a few Pacific populations which show similar frequencies to east Asians, all other groups in the Pacific area, including Australia, have values of GC*1F similar to GC*1S ranging from 27% to 40%. The GC*2 frequency in most populations varies from 20% to 30%. However, some Polynesian groups have values up to 40% and Australian Aborigines less than 10%. Among other alleles, GC*1A1 is found to be widely distributed among Australian Aborigines and Melanesians and occurs sporadically in Polynesians, Micronesians, and in the Lesser Sunda Islands. Four new alleles, GC*1C24, GC*1C35 Aborigine, GC*1A21, and GC*1A22 are described. The gene frequency data at the GC locus has been used to calculate Nei genetic distances between the populations studied.     

Investigations on the variability of four genetic serum protein markers (HP; TF, GC and PI subtypes) in Italy.

14 population samples from various Italian regions with a total of 2.577 unrelated male and female individuals were typed for four polymorphic serum protein polymorphisms: HP, and TF, GC and PI subtypes. The regional distribution of the allele frequencies of these four polymorphisms shows a considerable heterogeneity, which is for the most part statistically significant, thus indicating an obvious genetic variability of the population of the Italian Peninsula.     

Material for Studying the Gene Pools of Russia and Neighboring Countries: The Russian Population of the Pskov Oblast

The distributions of the genes and haplotypes for blood groups AB0, MN, Rhesus, P1, Lewis, and Kell–Cellano and biochemical markers of the genes of loci HP, GC, C"3, TF, 6PGD, GLO1, ESD, ACP1, and PGM1(including subtypes) were studied in 116 Russian subjects born in the Pskov oblast. Differences of this group from other Russian populations with respect to genetic structure were found.     

Transferrin subtypes in 51 Danish patients with hereditary haemochromatosis and in 847 normal subjects

Summary Transferrin (TF) subtypes were determined by isoelectric focusing in 51 unrelated Danish patients with hereditary haemochromatosis (HH) and in 847 normal subjects. The following TF phenotype frequencies were observed in HH patients and controls, respectively: TF*C1, 70.6% vs. 58.8%; TF*C2, 5.9% vs. 2.4%; TF* C3, 0% vs. 0.4%; TF*C1–2, 11.8% vs. 24.7%; TF*C1–3, 5.9% vs. 9.7%; TF*C2–3, 3.9% vs. 2.2%; TF*B–C1, 2.0% vs. 1.5%; TF*B–C2, 0% vs. 0.4%. None of these differences were statistically significant. There was no relationship between the TF subtypes and the clinical or paraclinical expression of disease in HH patients.     

Red cell enzyme and serum protein polymorphisms in South Korea

Two population groups in South Korea, one from Kwangju and one from Kangreung, were studied in regard to the erythrocyte enzyme polymorphisms GPT, ACP, GLO, ESD, 6PGD, ADA, AK, PGP and subtypes of PGM1 as well as regarding the serum protein variants of C3, HP, BF, PLG, AMY and the subtypes of GC, TF and PI. The results were compared with data of the population groups from the area of Cheju Island, Taejon and Seoul. The Korean population showed a rather high degree of genetic homogeneity.     

Population genetic studies in three Chinese minorities

Three minority ethnic groups from China (Mongolians, Koreans, Zhuang) were examined with respect to the genetic markers GLO, GPT, ACP, ESD, 6-PGD, PGM₁ subtypes, C3, and TF. Significant variations were noted for the gene frequencies of GLO, GPT, ESD, sub PGM₁ between Zhuang and Mongolians; for GPT, ACP, ESD, sub PGM₁ between Zhuang and Koreans; and for GLO between Mongolians and Koreans.     

Phylogenetic Relationships Among JC Virus Strains in Japanese/Koreans and Native Americans Speaking Amerind or Na-Dene

Abstract Many genetic studies using human mtDNA or the Y chromosome have been conducted to elucidate the relationships among the three Native American groups speaking Amerind, Na-Dene, and Eskimo-Aleut. Human polyomavirus JC (JCV) may also help to gain insights into this issue. JCV isolates are classified into more than 10 geographically distinct genotypes (designated subtypes here), which were generated by splits in the three superclusters, Types A, B, and C. A particular subtype of JCV (named MY) belonging to Type B is spread in both Japanese/Koreans and Native Americans speaking Amerind or Na-Dene. In this study, we evaluated the phylogenetic relationships among MY isolates worldwide, using the whole-genome approach, with which a highly reliable phylogeny of JCV isolates can be reconstructed. Thirty-six complete sequences belonging to MY (10 from Japanese/Koreans, 24 from Native Americans, and 2 from others), together with 54 belonging to other subtypes around the world, were aligned and subjected to phylogenetic analysis using the neighbor-joining and maximum-likelihood methods. In the resultant phylogenetic trees, the MY sequences diverged into two Japanese/Korean and five Native American clades with high bootstrap probabilities. Two of the Native American clades contained isolates mainly from Na-Denes and the others contained isolates mainly from Amerinds. The Na-Dene clades were not clustered together, nor were the Amerind clades. In contrast, the two Japanese/Korean clades were clustered at a high bootstrap probability. We concluded that there is no distinction between Amerinds and Na-Denes in terms of indigenous JCVs, although they are linguistically distinguished from each other.     

Two distinct genetic loci regulating class II gene expression are defective in human mutant and patient cell lines

Heterokaryons were prepared and analyzed shortly after cell fusion using two mutant class-II-negative human B cell lines (RJ 2.2.5 and 6.1.6) and a cell line (TF) from a patient with a class-II-negative Bare Lymphocyte Syndrome. The resulting transient heterokaryons were analyzed by using an anti-HLA-DR monoclonal antibody to assess the cell surface expression of HLA-DR (the major subtype of class II antigens) by immunofluorescence microscopy and by using uniformly 32P-labeled SP6 RNA probes in Northern blots and RNase protection assays to assess mRNA synthesis. We find that class II gene expression in a B cell line from a Bare Lymphocyte Syndrome patient (TF) is rescued by a B cell line which expresses class II antigens indicating that this disease, at least in part, is caused by a defect(s) in a genetic locus encoding a factor(s) necessary for class II gene expression. Secondly, reciprocal genetic complementation was demonstrated in the heterokaryons 6.1.6 x RJ 2.2.5 and TF x RJ 2.2.5 (but not in TF x 6.1.6) by detection of cell surface DR by immunofluorescence microscopy and by a novel class II mRNA typing technique which allows characterization of distinct class II alleles. Thus, the two mutants generated in vitro have defects at two different genetic loci encoding specific regulatory factors necessary for human class II gene expression. One of these mutant cell lines, but not the other, complements the defect in the patient cell line, TF.     

Phylogenetic relationships among JC virus strains in Japanese/Koreans and Native Americans speaking Amerind or Na-Dene

Many genetic studies using human mtDNA or the Y chromosome have been conducted to elucidate the relationships among the three Native American groups speaking Amerind, Na-Dene, and Eskimo-Aleut. Human polyomavirus JC (JCV) may also help to gain insights into this issue. JCV isolates are classified into more than 10 geographically distinct genotypes (designated subtypes here), which were generated by splits in the three superclusters, Types A, B, and C. A particular subtype of JCV (named MY) belonging to Type B is spread in both Japanese/Koreans and Native Americans speaking Amerind or Na-Dene. In this study, we evaluated the phylogenetic relationships among MY isolates worldwide, using the whole-genome approach, with which a highly reliable phylogeny of JCV isolates can be reconstructed. Thirty-six complete sequences belonging to MY (10 from Japanese/Koreans, 24 from Native Americans, and 2 from others), together with 54 belonging to other subtypes around the world, were aligned and subjected to phylogenetic analysis using the neighbor-joining and maximum-likelihood methods. In the resultant phylogenetic trees, the MY sequences diverged into two Japanese/Korean and five Native American clades with high bootstrap probabilities. Two of the Native American clades contained isolates mainly from Na-Denes and the others contained isolates mainly from Amerinds. The Na-Dene clades were not clustered together, nor were the Amerind clades. In contrast, the two Japanese/Korean clades were clustered at a high bootstrap probability. We concluded that there is no distinction between Amerinds and Na-Denes in terms of indigenous JCVs, although they are linguistically distinguished from each other.     

PI and TF subtypes in Chuetas (Majorcan Jews).

PI and TF subtypes were studied in a sample of 137 individuals of the Chueta population. In addition to the PI*M alleles, PI*S, PI*Z, and PI*F were observed in the PI system. In the TF system no TF*B or TF*D alleles were found. PI results were compared with those of some Jewish and non-Jewish populations. The relatively high frequency of PI*S is indicative of a substantial Spanish influence. There are no previous data available on TF*C subtypes in Jews. The very low TF*C3 frequency in Chuetas (lower than in Spain) indicates that this allele may be extremely rare or absent in other Jewish populations.     

Transferrin subtypes and variants in Germany; Further evidence for a Tf null allele

Summary Isoelectric focusing (IEF) with carrier ampholytes was used for the determination of transferrin C subtypes and transferrin B and D variants in a sample of 1125 unrelated individuals from Southern Germany. The observed TfC allele frequencies were Tf*C1=0.7872, Tf*C2=0.1365, and Tf*C3=0.0675. The rare C subtype C6 was observed twice. A new C subtype, called C10, was observed and identified by IEF with immobilized pH gradients. The rare C subtypes C4 and C8 were also studied by this method. TfB and TfD variants were found with a heterozygous frequency of 1.53%. One new TfD was found which is located between D1 and D2 and therefore named D1-2. Evidence for a Tf null allele was obtained in a child and the putative father; they were considered to be heterozygous for an allele Tf0. The theoretical exclusion rate for paternity examinations was calculated for the Tf system and found to be 17.95%.