Brief communication: immunoglobulin (Gm and Km) allotypes in two populations of Catalonia (Spain)

Serum samples from two populations of Catalonia, Spain, 208 from Olot (Gerona) and 209 from Tortosa (Tarragona), were typed for G1m (1, 2, 3, 17), G3m (5, 10, 11, 13, 14, 15, 16, 26), and Km (1). The Gm patterns of the Catalonian populations are characterized by the presence of four haplotypes, Gm 1,17;21,26 Gm 1,2,17;21,26 Gm 1,3;5,10,11,13,14,26 and Gm 3;5,10,11,13,14,26. The homogeneity for haplotype Gm 1,17;21,26 among our data and other European populations suggests the existence of an isofrequency line which starts from the Mediterranean zone of Iberian Peninsula and continues through the northwestern part of Europe. From this line a decreasing cline towards the south can be observed. For the haplotype Gm 1,2;17,21,26, affinities are observed between Catalonian populations and other populations from central Europe. This confirms the existence of a gradient towards low values from NW to SE. The presence of the typical Mongoloid haplotype Gm 1,3;5,10,11,13,14,26 is discussed in this paper. No significant differences in the frequencies of the Km1 allele were observed among the European populations.     

The frequencies of Gm(1), Gm(2), Gm(4), Gm(12), and Inv(1) in Hessen (Germany)

Summary The serum groups Gm(1) [Gm(a)], Gm(2) [Gm(x)], Gm(4) [Gm(f)]. Gm(12) [Gm(b)] and Inv(1) [Inv(1)] of 2000 sera of healthy blood donors from the land Hesse were examined. The results obtained were compared with those known until now. Three persons, not related to each other, possessed the extremely rare phenotype Gm(-1, 2, 4, 12) [Gm (a-x+b+f+)]. In 0.75% of the cases we found a discordant behaviour of the factors Gm(4) and Gm(12) [Gm(f) and Gm(b)].

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Zusammenfassung 2000 Seren von gesunden Blutspendern aus Hessen wurden bezüglich der Gamma-Globulin-Serumgruppen Gm(1) [Gm(a)], Gm(2) [Gm(x)], Gm(4) [Gm(f)]. Gm(12) [Gm(b)] und Inv(1) [Inv(1)] untersucht. Die gefundenen Resultate wurden mit den bisher bekannten verglichen. Drei miteinander nicht verwandte Personen wiesen den äußerst seltenen Phänotyp Gm(-1, 2, 4, 12) [Gm(a-x+b+f+)] auf. In 0.75% der Fälle fanden wir ein diskordantes Verhalten der Faktoren Gm(4) und Gm(12) [Gm(f) und Gm(b)].

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Director: Prof. Dr. W. Wachsmuth

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Director: Prof. Dr. W. Spielmann

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The nomenclature suggested by WHO at a round-table conference over genes, genotypes and allotypes of immunglobulins is used. The conference took place in Geneva on the 1965 31. 5. to the 5. 6. [5].

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With technical assistance of S. Mohs.     

Gm and Inv allotypes in a Gypsy sample.

Serum samples from 226 Gypsies were tested for Gm(1,2,4,5,8,10,11,14,17,21,23,25) and for Inv(1,2). The Gm phenotypes found are very numerous and the more frequent among this population are: Gm(4,5, 8,10,11,14,17,23,25) and Gm(1,2,4,5,8,10,11,14,17,21,23,25). All the phenotypes except three can be explained by nine haplotypes: Gm4,5,8,10,11,14,23,25, Gm1,4,5,8,10,11,14,23,25, Gm4,5,8,10,11,14,25, Gm1,17,21, Gm1,10,11,17,25, Gm1,2,17,21, Gm1,8,17,21, Gm1,8,17,21,23 and Gm1,5,10,11,14,17. The haplotypes Gm1,17,21, Gm1,2,17,21, Gm4,5,8,10,11,14,25 (with or without Gm[ 3]) are all three common among Caucasoids, Gm1,4,5,10,11,14,23,25 (common among Mongoloids) and Gm1,5,10,11,14,17 (common to Negroids). For the Inv system, this population possesses a very low frequency of Inv(1) and Inv(2).     

Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology

Biotransformation of the phytoestrogen [¹⁴C]genistein was investigated in male and female rats by application of narrow-bore radio-HPLC-MSⁿ (LCQ, Finnigan) to determine intermediates in metabolism. Urine contained five metabolites, Gm1–Gm5, 24 h after dosing by gavage with [¹⁴C]genistein (4 mg kg⁻¹). Structural analysis following ESI revealed molecular ions [M+H]⁺ of m/z 447, 449, 273, and 271 for metabolites Gm2, Gm3, Gm5 and genistein, respectively and an [M–H]⁻ of m/z 349 for Gm4. Metabolite structure was deduced by evaluation of product ion spectra derived from unlabelled and [¹⁴C]-labelled ions and sensitivity to treatment with β-glucuronidase. These studies indicated identity of metabolites with genistein glucuronide (Gm2), dihydrogenistein glucuronide (Gm3), genistein sulphate (Gm4) and dihydrogenistein (Gm5). Detection of the β-glucuronidase resistant major metabolite Gm1 by ESI was poor and so was analysed by negative ion APCI; this revealed a deprotonated molecular ion of m/z 165 which had chromatographic and mass spectral properties consistent with authentic 4-hydroxyphenyl-2-propionic acid, a novel metabolite of genistein. In vitro metabolism studies with anaerobic caecal cultures derived from male and female rats revealed metabolism of genistein to Gm1 via Gm5 and an additional metabolite (Gm6) which was identified from product ion spectra as 6′-hydroxy-O-desmethylangolensin. Biotransformation of genistein by both isolated hepatocytes and precision-cut liver slices was limited to glucuronidation of parent compound. Commonality of genistein metabolites found in rats with those reported in man suggest similar pathways of biotransformation, primarily involving gut micro-flora.     

Purification and characterization of eight peptides from Galleria mellonella immune hemolymph

Defense peptides play a crucial role in insect innate immunity against invading pathogens. From the hemolymph of immune-challenged greater wax moth, Galleria mellonella (Gm) larvae, eight peptides were isolated and characterized. Purified Gm peptides differ considerably in amino acid sequences, isoelectric point values and antimicrobial activity spectrum. Five of them, Gm proline-rich peptide 2, Gm defensin-like peptide, Gm anionic peptides 1 and 2 and Gm apolipophoricin, were not described earlier in G. mellonella. Three others, Gm proline-rich peptide 1, Gm cecropin D-like peptide and Galleria defensin, were identical with known G. mellonella peptides. Gm proline-rich peptides 1 and 2 and Gm anionic peptide 2, had unique amino acid sequences and no homologs have been found for these peptides. Antimicrobial activity of purified peptides was tested against gram-negative and gram-positive bacteria, yeast and filamentous fungi. The most effective was Gm defensin-like peptide which inhibited fungal and sensitive bacteria growth in a concentration of 2.9 and 1.9 microM, respectively. This is the first report describing at least a part of defense peptide repertoire of G. mellonella immune hemolymph.     

The effect of the interaction of heavy and light chains of IgG on the Gm and Inv antigens

Studies of isolated polypeptide chains, of reconstituted, and of intact IgG show that the antigens present on the Fab fragment, Gm (3), Gm (4), and Inv (1), depend upon the interaction of heavy and light chains for their full antigenic expression, while the antigens of the Fc portion of the heavy chain, Gm (1), Gm (5), Gm (13), and Gm (14), have the same antigenicity in intact IgG, in isolated heavy chains, and in reconstituted IgG. Hybridization experiments using Bence-Jones protein light chains indicate that different homogeneous populations of light chains differ in their ability to restore Gm (3) and Gm (4) antigenicity and that this ability is independent of light-chain antigenic type.The investigations reported in this paper were supported in part by National Institutes of Health Grant GM 07214.Recipient of support from National Institutes of Health Training Grant 2T1 GM 226.     

Identification and mapping of an AFLP marker linked to Gm7, a gall midge resistance gene and its conversion to a SCAR marker for its utility in marker aided selection in rice

We have identified an AFLP marker SA598 that is linked to Gm7, a gene conferring resistance to biotypes 1, 2 and 4 of the gall midge ( Orseolia oryzae), a major dipteran pest of rice. A set of PCR primers specific to an RFLP marker, previously identified to be linked to another gall midge resistance gene Gm2, also amplified a 1.5-kb (F8LB) fragment that is linked to Gm7. Gm7 is a dominant gene and non-allelic to Gm2. Hybridization experiments with clones from a YAC library of Nipponbare, a japonica variety, a BAC library of IR-BB21, an indica variety, and cosmid clones encompassing Gm2 from Phalguna, an indica variety, with F8LB and SA598 as probes, revealed that Gm7 is tightly linked to Gm2 and is located on chromosome 4 of rice. SA598 was sequenced and the sequence information was used to design sequence-characterized amplified region (SCAR) primers. The potential use of these SCAR primers in marker-aided selection of Gm7 in a rice breeding program has been demonstrated.     

Gm and Km(Inv) frequencies in two Roumanian populations

Summary Serum samples from 170 unrelated individuals from the Suceava District of Roumania and from 199 unrelated individuals from Bucharest, Roumania were tested for Gm(1, 2, 3, 5, 6, 13, 14, 17, 21) and Km(1)[Inv(1)]. Selected samples were also tested for Gm(15) and Gm(16).The frequencies of the three common Caucasoid haplotypes, Gm ^{3, 5, 13, 14}, Gm ^{1, 17, 21}, and Gm ^{1, 2, 17, 21} in these two populations were found to be similar to those in neighboring Slavic states and Hungary. Racial admixture was evidenced by the presence of the Gm ^{1, 13, 15, 16, 17} and Gm ^{1, 3, 5, 13, 14} haplotypes, which are primarily Mongoloid, and the Gm ^{1, 5, 13, 14, 17} haplotype which is primarily Negroid.Comparisons of these data with those from earlier studies of populations from Central Europe indicate that the frequency of the Gm ^{3, 5, 13, 14} haplotype within this region is high and essentially uniform. Published data for several blood group systems also indicate essentially uniform distributions of frequencies in this region. It is suggested that this region may be the center of a clin that radiates from it.Post-Doctoral Fellow supported by NIH Training Grant Gm07004.     

Association between immunoglobulin allotypes and pulmonary tuberculosis

In a sample of n = 133 non-related patients suffering from pulmonary tuberculosis, Gm and Km typings have been carried out and compared with healthy controls from the same geographical area. All the Gm allotypes tested were found to be more preponderant in the patients than in the healthy controls and these differences were found to be statistically significant for Gm (1) and Gm (5) only and not for the other immunoglobulin allotypes e.g. Gm (2). The frequency of Km (1) was lower and that of Km (3) was higher in the patients than in the controls. These differences were, however, statistically not significant.     

Imbalance in recruitment of IgG (Gm) allotype-producing B-cell subsets from blood to brain in multiple sclerosis

In Gm3/Gm3 homozygous multiple sclerosis (MS) patients, in vitro production of the G1m(3) allotype of IgG1 induced by the T-independent polyclonal B-cell activator Salmonella paratyphi B (SPB) was lower than that of normal individuals of the same Gm phenotype. In contrast, lymphocytes from Gm1/Gm3 heterozygous MS patients responded to the same stimulus with a significantly increased G1m(3) allotype synthesis not observed in normal individuals of the same phenotype. The high level of intrathecal IgG1 production observed in MS patients might be achieved by a selection at the blood-brain barrier of some peripheral T-independent B-cell clones which in Gm3/Gm3 homozygous would bear the G1m(3) allotype, hence a peripheral depletion of this subset, whereas in Gm1/Gm3 heterozygous a preferential admission of the G1m(1)-producing B-cells would lead to a preferential synthesis of this allotype in the central nervous system and to a relative increase of G1m(3) production by the remaining peripheral B cells.     

Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now possible to define common Gm haplotypes in Caucasians by RFLP analysis. This method provides a useful adjunct to serological allotyping and indeed has several important advantages over traditional serology: it allows confident Gm assignment and the definition of homozygous and heterozygous Gm arrangements, is highly reproducible, and is readily executed in any molecular genetic laboratory.     

Characteristics of Mongoloid populations based on the human immunoglobulin allotypes

Since the discovery of Gm ab3st haplotype which characterizes Mongoloid populations in 1966, the distribution of the genetic markers of immunoglobulins (Gm) among the Mongoloid populations scattered from Southeast Asia through East Asia to South America has been investigated and concluded as follows: 1) Mongoloid populations characterized by the four Gm haplotypes, ag, axg, ab3st and afb 1b3 are divided into two groups on the basis of analysis of genetic distances based on the Gm haplotype frequencies: one is a southern group characterized by a remarkably high frequency of Gm afb 1b3 and a low frequency of Gm ag and the other is a northern group characterized by a high frequency of Gm a and an extremely low frequency of Gm afb 1b3. 2) Populations in China, mainly Han including minority nationalities, show remarkable heterogeneities from north to south, in sharp contrast to Korean and Japanese populations showing homogeneities, respectively. The center of dispersion of the Gm afb 1b3 characterizing southern Mongoloids must exist in Guangxi and Yunnan area in the southwest China. 3) The Gm ab3st gene found in the highest incidence among the north Baikal Buriats flows in all directions. The gene, however, shows precipitous drop which occur from mainland China to Southeast Asia and from North to South-America, although the Gm ab3st gene is still found in high incidences among Eskimos, Yakuts, Tibetans, Olunchuns, Koreans, Japanese and Ainus. On the other hand, the gene is introduced into Huis, Uighurs, Indians, Iranians and far Hungarians.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glycosphingolipid levels in an unusual neurovisceral storage disease characterized by lactosylceramide galactosyl hydrolase deficiency: lactosylceramidosis

The glycosphingolipid composition of brain and visceral tissue from a patient with an unusual neurovisceral lipid storage disease, characterized by a lactosylceramide galactosyl hydrolase deficiency, was determined. Analyses of erythrocytes, plasma, bone marrow cells, urine sediment, and liver biopsy from the patient were compared with those of normal infantile controls. Abnormally high levels of lactosylceramide (GL-2a) were found in these samples. Subsequent studies on spleen, liver, kidney, lymph nodes, and adrenal gland confirmed this finding and clearly showed that the metabolism of hematoside (Gm3) and glucosylceramide (GL-1a) was also affected. The accumulation of GL-1a and Gm3 was most pronounced in spleen, but it was not of the order seen in the spleens of patients with Gaucher's disease that were studied for comparison. Since the disease was primarily neurological in nature, fresh-frozen brain was also studied. The level of GL-2a in gray matter was equal to that of galactosylceramide (GL-1b), and elevated amounts of GL-1a, asialo-Gm2, Gm2, and Gm3 were also found; the only major abnormality in white matter was the accumulation of GL-2a and lesser amounts of the gangliosides Gm3 and Gm2. Chemical and enzymic evidence suggests the use of the term "lactosylceramidosis" for this disease.     

Immunoglobulin (Gm) allotypes in a sample of Canadian Ashkenazic Jews

Gm typing on the serum specimens of 507 Ashkenazic Jews (pre-dominantly of Polish-Russian ancestry) from Toronto, Canada has established the presence of haplotypes Gm3;5, Gm1;21, Gm1,2;21, and Gm1,17;5, and the absence of haplotypes Gm1;13,15,16, Gm1;5,6, and Gm1;5,6,24 which have been found in other Jewish peoples. It is suggested that Ashkenazic populations have lower frequencies of haplotype Gm1,17;5 than non-European Jewish populations, and that some eastern European Jewish populations have acquired the Gm1;13,15,16 haplotype through gene flow from Central Asia. Thus Jewish populations show differences in the Gm system; many of the differences may be in the direction of similarities to neighbouring non-Jewish populations.     

Distribution of Gm and Km allotypes among ten populations of Assam, India

Serum samples from ten endogamous populations of Assam, India-Brahmins, Kalitas, Kaibartas, Muslims, Ahoms, Karbis, Kacharis, Sonowals, Chutiyas, and Rajbanshis-were typed for G1m (1, 2, 3, 17), G3m (5, 10, 11, 13, 14, 15, 16, 21, 26), and Km (1). Among Brahmins, Kalitas, Kaibartas, Muslims, Ahoms, Sonowals, Chutiyas, and Rajbanshis, five different Gm haplotypes were found: Gm1,17;21,26; Gm1,17;10,11,13,15,16; Gm1,2,17;21,26; Gm1,3;5,10,11,13,14,26; and Gm3;5,10,11,13,14,26. Kacharis and Karbis show only four of these haplotypes: Gm3;5,10,11,13,14,26 is absent among them. The intergroup variability in the distribution of these haplotypes is considerable, which can be explained by the ethnohistory of these populations. Genetic distance analysis, in which five Chinese population samples were included, revealed the existence of three main clusters: 1) North and Central Chinese; 2) Kalitas, Kaibartas, Chutiyas, Rajbanshis, Muslims, and Brahmins; and 3) Ahoms, Sonowals, Kacharis, South Chinese, and Karbis. The clusters suggest some genetic relation between these four Assamese populations and South Chinese, which is again understandable considering the ethnohistory of the populations of Northeast India. In the Km system, too, a remarkable variability is seen in distribution of phenotype and allele frequency.     

Distribution of Gm and Km allotypes among five populations in China

Serum samples from five populations in China [173 from Huhehote (Naimengu Zhizhiqu), 195 from the Beijing area, 131 from Hefei (Anhui Province), 155 from Hangzhou (Zhejiang Province), and 152 from Guangzhou (Guangdong Province)] were tested for G1m(1, 2, 3, and 17), G2m(23), G3m(5, 10, 11, 13, 14, 15, 16, 21, and 26), and Km(1). The Gm pattern of the Chinese populations are characterized by the presence of four haplotypes, Gm1, 17;..;21, 26, Gm1, 2, 17;..;21, 26, Gm1, 17;..;10, 11, 13, 15, 16, and Gm1, 3;23;5, 10, 11, 13, 14, 26, which are characteristic of Mongoloid populations. Agreement was obtained in all Chinese samples between the observed and expected frequencies on the basis of the Hardy-Weinberg equilibrium of phenotypes. Heterogeneity tests of the haplotypic distributions among the five populations showed no significant differences in the distributions of Gm phenotypes between Huhehote and Beijing nor between Hefei and Hangzhou, whereas highly significant differences were observed among the three districts: northern part (Huhehote and Beijing), central part (Hefei and Hangzhou), and southern part (Guangzhou). The data indicate a south to north genocline, ranging from Huhehote to Guangzhou in which Gm1, 17;..;21, 26 changes from 0.471 to 0.183, Gm1, 17;..;10, 11, 13, 15, 16 from 0.097 to 0.033, and Gm1, 3;23;5, 10, 11, 13, 14, 26 from 0.229 to 0.730. In contrast to the Gm system, no significant regional differences in the frequencies of the Km1 allele were observed among the five populations.     

Immunoglobulin allotypes in patients with nasopharyngeal carcinoma

Gm phenotypes and the Km(1) allotype were studied in Tunisian patients with nasopharyngeal carcinoma (NPC). A highly significant association was found between the Km(1) allotype and the NPC disease. Two rare Gm haplotypes, Gm(1, 17; 11, 15, 21) and Gm(1, 3, 5, 11), were found to be significantly increased among the NPC patients.     

Certain characteristics of isolation of human myelomic IgG of different subclasses and their distribution according to the allotypes, subclasses and types of light chain]

A combination of the methods of preparative electrophoresis in agar gel and of the ion-exchange chromatography on DE-32 cellulose permitted to obtain 32 immunochemically pure human myelomic IgG. The proteins of the first three subclasses were obtained by elution in the 0.01 phosphate buffer at pH 7.6. IgG4 was eluted with the increase of the gradient to 1 M NaCl in the phosphate buffer. Of the 32 human myelomic IgG 26 represented IgG1,4--IgG2, 1--IgG3, and 1--IgG4. Among the 26 IgG1 11 were of the Gm(a) allotype, and 15 proteins had the Gm(f) determinant; one IgG2 protein was Gm(n+) and 3--Gm(n-). One IgG3 protein was referred to the Gm(b) variant. The majority of the IgG proteins of the subclass I had chi-type of the L-chains, and the chi: lambda ratio constituted 2.71.     

Identification of germplasm with stacked QTL underlying seed traits in an inbred soybean population from cultivars Essex and Forrest

Soybean (Glycine max (L.) Merr.) seed provides valuable oil (~200 g/kg) and protein (~400 g/kg) co-products. Seed composition variations result from several quantitative trait loci (QTL) that act through development. The objectives here were to identify loci underlying seed traits in the Essex × Forrest (EF94)-derived recombinant inbred line (RIL) population which has low frequencies of marker polymorphisms. Seed weight, protein, and oil were measured over 3 years: 2001, 2003, and 2005. Essex’s seeds were larger (141 mg/seed), higher in protein (406 g/kg), and lower in oil (190 g/kg) than Forrest’s (115 mg/seed, 395 g protein/kg, and 203 g oil/kg). Marker analysis included 413 markers for trait associations used for ANOVA, interval mapping, and composite interval mapping. Eleven QTL in nine genomic regions were associated (LOD >2; P < 0.0077) with seed traits. Two QTL, for mean protein and seed size, were clustered on linkage group (LG) E (chromosome Gm16). QTL for protein content alone were found on LG C2 (Gm6), LG D1b (Gm2), LG H (Gm12), and LG I (Gm20). The alleles from Essex, the high-protein parent, underlay higher protein (4–10 g/kg) at four of five loci. A QTL for mean oil was found on LG A2 (Gm18) and on LG I (Gm 20). The alleles from Forrest underlay higher oil (3–4 g/kg). Five separate QTL for mean seed weight were found on LG A1 (Gm05), LG N (Gm15), two on LG B1 (Gm11) and one on LG N (Gm3). The alleles from Essex underlay greater seed weight (0.4–0.66 g/100 seeds). The QTL positions were consistent with reported loci. Germplasm that contained all five beneficial alleles at the QTL underlying protein was significantly higher in protein and yield than Essex (409.7–412.3 g/kg) and included RILs 49 and 62. The germplasm identified can be useful for further breeding of the many traits and QTL measured in each line.