Genetic polymorphism of human complement C4 and detection of heterozygotes.
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Lymphocyte surface antigens from spleen cells of several mouse strains were studied by cell surface radioiodination, extraction with detergent incubation with various antisera, and separation of complexes using protein A-containing staphylococci as a solid phase adsorbent. Complexes were then dissociated and analyzed by polyacrylamide gel electrophoresis in the presence of sodium diodecyl sulfate. Using this technique and an alloantiserum prepared in C57BL mice against CBA spleen cells, four distinct specific peaks of radioactivity were found with CBA spleen cells. These corresponded to H-2 and Ia antigens, immunoglobulin light chain, and a heavy chain previously proposed to be the murine homolog of the human delta chain. With the same serum, B10.BR spleen cells revealed only H-2 and Ia antigens, whereas C57BL.Ige (allotype congenic) spleen cells showed only the light chain and "delta" chain peaks. Depletion of immunoglobulin from the surface-iodinated preparations resulted in removal of the light chain and "delta" chain peaks. The tissue distribution and membrane expression of this "delta" chain antigen was then studied by indirect immunofluorescence with various C57BL derived alloantisera and lymphoid cells from C57.Ige allotype congenic mice. Significant numbers of positive cells were found in spleen, lymph nodes, and Peyer's patches, whereas few if any positive were found in bone marrow or thymus. No reaction was found between this molecule and alloantisera to any of the previously described immunoglobulin allotypes. It is proposed that these alloantisera to spleen cells recognise one allelic form of the murine "delta" chain coded for by a gene locus closely linked to the known structural genes for mouse immunoglobulin heavy chains. The designation Ig-5 is proposed for this new immunoglobulin heavy chain locus.
The gene frequencies in samples of two language groups from Afghanistan, comprising 104 Pushtu and 179 Dari subjects living in Kabul, have been examined for 24 loci. Some systems suggest greater affinity to the west (e.g. the MS gene combination, the esterase D2 allele), some to the east (e.g. the K blood group), while others are intermediate between those of India and the Orient on the one hand, and Europe and the West on the other. In general, the gene frequency levels are much as would be expected from the geographical position of the country. The two language samples are essentially similar in gene frequency, so any earlier gene frequency differences that may have existed between the language groups are no longer distinguishable. However, the amount of heterozygosity shows that the Kabul population is not yet homogeneous and that the two endogamous linguistic groups remain disparate to some extent.
In a sample of 150 Sukuma from north central Tanzania, immunoglobulin G, M, A, and E levels were studied in relation to the phenotypes in 22 polymorphic systems. No strong associations were detected, though there is a suggestion of an association between IgG and haptoglobin type, with elevation of mean levels in heterozygotes.
We studied the phosphoglucomutase phenotype in relation to fertility parameters in a consecutive series of 204 women who had delivered a normal live-born child in Rome. A highly significant association was found between age of the women and phosphoglucomutase phenotype, suggesting a reduced rate of reproduction among women of phosphoglucomutase Type 1. Previous spontaneous abortion appears related to both age and phosphoglucomutase enzymatic type. An increased incidence of abortion in women of older ages was observed only in phosphoglucomutase Type 1. Gestational duration and fetal intrauterine growth rate are also significantly associated with maternal phosphoglucomutase phenotype. The pattern is complex, but also in this instance the influence of maternal age was evident. Considered altogether, the data suggest that phosphoglucomutase may have an important role in zygote development and survival through the whole span of intrauterine life.
Amino acid sequence analysis of a b4 light chain from a rabbit homogeneous antistreptococcal antibody revealed the presence of two amino acid substitutions in the constant region not previously reported for these positions. These interchanges, consisting of serine for alanine at position 121 and leucine for glutamine at position 124, were also present in about 30% of the pooled b4 light chains isolated from pooled IgG from the rabbit (4539) that produced the homogeneous antibody. In addition, these interchanges (b4var) were found, always at the same levels, in varying percentages in nonimmune or early immune bleedings from related rabbits in this pedigreed family and could be traced for five generations. The inheritance pattern of b4var was consistent with autosomal codominant inheritance.
Light chains isolated from normal immunoglobulin of unimmunized mice were analyzed by gel isoelectric focusing. Examination of the focusing patterns of light chains from nine inbred mouse strains showed that six of the strains (SWR/J, C3H/HeJ, DBA/1J, A/J, CBA/J, and C57BL/6J) possessed a virtually identical spectrum of focusing bands, while the remaining three strains (RF/J, AKR/J, and C58/J) showed clear differences involving several bands. Analysis of the light chains of individual SWR/J, C58/J, and F1 hybrid mice indicated that the differences in focusing pattern were inherited in a simple codominant fashion. A new procedure was developed for the rapid analysis of light chains from small quantities of serum.
Genic polymorphism at sixteen enzyme loci of four different chromosomal races of Solenobia triquetrella (bisexual, two diploid parthenogenetic races and tetraploid parthenogentiic) has been studied by starch gel electrophoresis. Isolated small diploid bisexual populations have rather uniform allele frequencies at all loci which we have studied. Diploid and tetraploid parthenogenetic individuals of this species are in general as heterozygous as bisexual ones. All parthenogenetic local populations are different from each other in the Alps. These parthenogenetic genotypes cannot be derived from a common ancestor through single mutations but rather bear evidence for a polyphyletic origin of parthenogenesis in Solenobia triquetrella. In the marginal distribution areas of the species in northern Europe single genotypes are spread over far larger areas than in the mountain regions of central Europe. This may be due to the old origin of parthenogenesis and polyploidy in northern Europe. No new parthenogenetic and polyploid strains have lately arisen in the regions outside of the Alps.
The cytochromes P450 participate in the metabolic activation of precarcinogens. Recent results reveal that many P450 genes are polymorphically distributed. Different investigators have tried to link polymorphic variants of the CYP1A1, CYP2D6 and CYP2E1 genes to the incidence of cancer, particularly lung cancer, in Asian and Caucasian populations. In the current overview we briefly summarize this research. It appears that interesting functionally linked interindividual differences in the CYP1A1 gene have been found and could be of importance in understanding differences in susceptibility to lung cancer. On the other hand, the data presented regarding CYP2D6 and CYP2E1 are less promising. We also describe interethnic differences in the P450 gene structures as a major obstacle for extrapolation of results between different ethnic groups.
Six plasma eserine resistant esterase phenotypes were observed in a population of 1438 dogs consisting of 38 breeds. Analysis of parentage records of the dogs examined revealed that the phenotypic variation of eserine resistant esterases was controlled by 3 codominant alleles ESA, ESB and ESC at one autosomal locus. The gene frequency of ESB was high in most of the breeds examined. Allele ESC was only seen in 5 Japanese native breeds, Akita, Shikoku, Hokkaido, Shinshu-Shiba and Mino-Shiba, and in a Spitz dog. Allele ESA has a low frequency in Japanese breeds but a higher frequency in some of the European breeds tested.
A modified electrophoretic system for the determination of C4 polymorphism has been found with which the new allotype F1 could be detected. The system has been applied to the population distribution of C4 in 266 unrelated Germans, further to association and linkage studies. Gene frequency was 0.3985 for C4F, 0.5526 for C4S and 0.0489 for the rare C4 genes. In the population sample, significant association between Bf and C4 but no indication for close association between C4 and GLO I has been found. In the families HLA, Bf and C4 segregated together.
1. A method has been devised for the detection after starch-gel electrophoresis of phosphoglycolate phosphatase (PGP) isozymes. 2. PGP isozymes can be detected in all human tissues including red cells, lymphocytes and cultured fibroblasts. The highest activities occur in skeletal muscle and cardiac muscle. 3. PGP is a relatively specific phosphatase which shows enhanced activity in the presence of mercaptoethanol at a neutral pH.4. Six different commonly occurring electrophoretic types of PGP have been identified. Family studies indicate that they are determined by three alleles at an autosomal locus (PGP). 5. The gene frequencies of PGP1, PGP2 and PGP3 in a random sample of Europeans were 0.826, 0.129 and 0.045 respectively. 6. The three-banded isozyme patterns seen in heterozygotes suggest that PGP is a dimeric enzyme.
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PGM3 activity was investigated in 150 'Boerbok' goats and 132 Angora goats by means of horizontal starch gel electrophoresis. In 'Boerbok' goats no polymorphism was found. In Angora goats three different phenotypes have been recognized: F, S, and FS. The results suggest the occurrence of two common alleles: PGM3-F and PGM3-S at an autosomal locus with frequencies of 0.6176 and 0.3824, respectively.
PGM3 activity was investigated by means of horizontal starch gel electrophoresis. In the pig of the German Landrace three different phenotypes have been recognized: F, S and FS. Family studies suggest the occurrence of at least two alleles--PGM3F and the PGM3S at an autosomal locus.
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