Autosomal Codominant Alleles Research Articles

Orosomucoid (alpha-1 acid glycoprotein) phenotyping by use of immobilized pH gradients with 8 M urea and immunoblotting. A new variant encountered in a population study.

Orosomucoid (ORM) phenotyping has been performed on 329 unrelated Swiss subjects, using immobilized pH gradients with 8 M urea and 2% v/v 2-mercaptoethanol followed by immunoblotting. After desialylation the band patterns of ORM confirmed that the polymorphism of the structural locus ORM1 is controlled by three codominant autosomal alleles (ORM1*F1, ORM1*S and ORM1*F2). One rare and one new allele were detected. The rare variant, tentatively assigned to the second structural locus ORM2, is observed in a cathodal position and named ORM2 B1. The new variant, tentatively assigned to the first structural locus ORM1, is observed in a region located between ORM1 S and ORM1 F2, and named ORM1 F3. Moreover, the pI values of the ORM variants have been measured accurately with Immobiline Dry Plates (LKB): they were found to be within the pH range 4.93-5.14.

Natural history of alpha-1-protease inhibitor deficiency

Alpha-1-protease inhibitor (A1PI) exists in over 30 biochemical variants (the P₁ system), inherited as autosomal codominant alleles. Homozygotes of P₁ type Z have only 10 to 20 percent of the normal serum A1PI concentration and have a high risk of developing pulmonary emphysema. A1PI is an inactivator of polymorph lysosomal elastase, the unopposed action of which may damage the lung. Cigarette smoking is an important additional risk factor. Neonatal hepatitis occurs in 10 to 20 percent of P₁, type Z persons, and cirrhosis develops in a number of them in later childhood or in adult life. In heterozygotes of P₁ type MZ, pulmonary or hepatic disease may also develop, though they are at lesser risk than type Z homozygotes. Specific A1PI replacement therapy derived from human plasma is now available and has been administered to P₁ type Z patients by weekly intravenous infusion without adverse effects. A controlled clinical trial would be desirable, though this would be attended by organizational and economic problems.

Natural history of alpha-1-protease inhibitor deficiency

Alpha-1-protease inhibitor (A1PI) exists in over 30 biochemical variants (the P i system), inherited as autosomal codominant alleles. Homozygotes of P i type Z have only 10 to 20 percent of the normal serum A1PI concentration and have a high risk of developing pulmonary emphysema. A1PI is an inactivator of polymorph lysosomal elastase, the unopposed action of which may damage the lung. Cigarette smoking is an important additional risk factor. Neonatal hepatitis occurs in 10 to 20 percent of P i type Z persons, and cirrhosis develops in a number of them in later childhood or in adult life. In heterozygotes of P i type MZ, pulmonary or hepatic disease may also develop, though they are at lesser risk than type Z homozygotes. Specific A1PI replacement therapy derived from human plasma is now available and has been administered to P i type Z patients by weekly intravenous infusion without adverse effects. A controlled clinical trial would be desirable, though this would be attended by organizational and economic problems.

Pattern of inheritance of a larval tubercle-colour polymorphism in Hyalophora Columbia of northwestern Ontario (Lepidoptera: Saturniidae)

A fifth instar larval colour polymorphism in H. Columbia from northwestern Ontario had been previously indicated indirectly from the progeny of interspecific matings. The polymorphism has been confirmed directly by a recent collection of larvae from the vicinity of Kenora, Ontario. Results from six different mating classes suggest that the dorsal thoracic tubercle colours are determined by a pair of codominant autosomal alleles such that TRTR produces a red colour, TRTy a reddish-orange colour, and TyTy a yellow colour. Epistatic interaction with abdominal tubercle determining factors is hypothesized to cause larvae with white instead of yellow abdominal tubercles to have dorsal thoracic tubercles that are pinkish red, pale pinkish red, and pale yellow.Key words: Hyalophora, tubercle colour, polymorphism.

Application of plasminogen polymorphism to forensic hemogenetics.

Plasminogen polymorphism (PLG) has attained considerable importance in forensic hemogenetics. PLG comprises two common, codominant autosomal alleles, PLG*A and PLG*B, more than 18 variants, and the silent allele PLG*Q0. Isoelectric focusing followed by functional or immunochemical detection seems to be the optimal method for the determination of phenotypes. PLG*A is the most common allele in all populations, having its highest frequency in Mongoloids, Amerindians and Eskimos, the lowest in Caucasoids. The functionally inactive plasminogen M5 so far has been seen exclusively in Japanese individuals. Silent PLG alleles were only observed in the heterozygous state. No clear differences in functional activity or plasma level could be ascertained for any of the other allotypes. PLG polymorphism is now widely used for many haemogenetic investigations. From the allele distribution in European Caucasoids a single exclusion chance of 17.2% for non-fathers in paternity testing may be calculated. The major prerequisites of a new genetic marker in the parentage expertise, established Mendelian inheritance, favorable distribution of common alleles, low frequency of silent alleles, and simple reproducible typing technology, are fulfilled.

The transferrins from Xenopus laevis, Xenopus borealis and their hybrids

1. 1. The transferrins of Xenopus laevis and Xenopus horealis are polymorphic. Electrophoresis can distinguish between the two Xenopus species. Differences in electrophoretic mobility are not explained by differences in sialic acid or iron content of the molecule; they are of genetic origin. 2. 2. X. laevis has two transferrins or one of these two. Breeding experiments between the two species support the argument that in X. laevis one locus with two autosomal codominant alleles is present. X. borealis displays two major transferrins: the two transferrins could be coded by one or two homozygous genes. 3. 3. The mol. wt of X. laevis transferrin is about 85,000.

Three new orosomucoid (ORM) variants revealed by isoelectric focusing and print immunofixation

Phenotypes of orosomucoid (ORM) in human sera have been analysed by isoelectric focusing and print immunofixation. After neuraminidase treatment the band patterns indicated that the polymorphism of the structural locus ORM1 is controlled by three autosomal codominant alleles. According to the previous nomenclature they were called ORM1F1, ORM1F2, and ORM1S. In a study of 272 unrelated individuals from southern Germany, five of the six expected common ORM1 subtypes were observed. Furthermore, we found three ORM variant phenotypes which have not been reported previously. These variants were characterized by additional bands in a cathodal position. One variant had additional double bands and presumably represents a rare ORM1 variant named ORM1S1. Two variants had additional single bands. They were assigned tentatively to the ORM2 gene locus. While the common gene product of ORM2 may be called ORM2A, the two variants are named ORM2B1 and ORM2B2, respectively. ORM2B1 has, thus far, been found only in a single individual; the variants ORM1S1 and ORM2B2 were found in a father-child pair and a mother-child pair, respectively. The frequency for variants tentatively assigned to the ORM2 locus is very low and was calculated to be 0.0037.

NADH diaphorase polymorphism in goat erythrocytes.

This paper describes for the first time polymorphism of the erythrocyte diaphorase in goats. Three diaphorase 1 phenotypes were observed in the red cells of goats. Breeding data indicated that polymorphism was controlled by two autosomal codominant alleles, DiaF and DiaS, the frequencies of which were determined in 14 different Spanish breeds of goat.

The inheritance mode of simian‐type E, F, and GH blood groups in cynomolgus monkeys

The mode of inheritance of four different red cell antigens (Ecy, Fcy, Gcy, and Hcy), detected by alloimmune reagents prepared by us for the cynomolgus monkey, was studied. The results of the segregation analysis suggest that each antigen is inherited in an autosomal dominant manner. Both the random sample analysis and family study revealed that two of these red cell antigens (Ecy and Fcy) probably represent the products of two independent genes while the expression of the other two antigens (Gcy and Hcy is governed by two autosomal codominant alleles. Thus, three simian-type blood group systems could be demonstrated by the four newly developed alloimmune reagents. We use the following nomenclature for these blood groups: the E and F blood groups, each with two phenotypes, antigen positive (E and F) and antigen negative (e and f), and the GH blood group having three phenotypes (G, H, and GH).

A new alpha 2HS-glycoprotein typing by isoelectric focusing.

Isoelectric focusing (pH 4.0-5.0) of serum alpha 2HS-glycoprotein on polyacrylamide gels has been found to be a useful tool in population genetics and forensic science. Using this method, we isolated three common types, alpha 2HS 1-1, alpha 2HS 2-1 and alpha 2HS 2-2, and showed that alpha 2HS types are determined by two autosomal codominant alleles, alpha 2HS1 and alpha 2HS2. The method is simple, fast and easy to perform. Results of typing for the two alleles, alpha 2HS1 and alpha 2HS2, are described for a Japanese population sample (n = 1003).

Genetic analysis of enzyme polymorphisms in herring (Clupea harengus L.).

Single pair matings were performed to confirm the genetic basis of electrophoretic variants of several enzyme systems in north-east Atlantic herring (Clupea harengus) collected in spawning condition from the North Irish Sea. Mendelian inheritance of codominant autosomal alleles was established for Aat-2, Idh-2, Ldh-2 and Pgi. Crosses among Fum-1, Idh-1 and Sod homozygotes produced only homozygous offspring. This study also permitted the investigation of linkage relationships between polymorphic loci. Linkage was not observed between any two loci in the 13 pairwise comparisons made. This analysis constituted the first investigation of linkage relationships in the species.

A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele Amphibian). I. Lactate dehydrogenase-B and glucose-6-phosphate dehydrogenase

On starch gel electrophoresis of erythrocyte hemolysates of Pleurodeles waltlii (Urodele Amphibian), both lactate dehydrogenase-B (LDH-B) and glucose-6-phosphate dehydrogenase (G6PDH) show polymorphism that depends on a pair of autosomal codominant alleles, confirmed by analysis of gynogenesis progeny. Diploid gynogenesis results from fusion of the female pronucleus with the second polar body. The heterozygous state of a female for a given character is maintained in certain progeny when crossing-over occurs between the locus in question and the centromere. So the high proportion of heterozygotes (45.7% for LDH-B and 76% for G6PDH) indicates the high frequency of crossing-over and hence the large distance between each of the loci and the centromere.

Biochemical genetics of macaques. III. Inheritance of carbonic anhydrase II polymorphism in rhesus monkeys.

The primary function of mammalian red-cell carbonic anhydrase (EC 4.2.1.1; carbonate dehydratase) is to catalyze the hydration of carbon dioxide released in body tissues and to catalyze the dehydration of bicarbonate ions in the lungs. Three isozymes designated CA I (or B), CA II (or C), and CA I I I are known in mammals , and each is coded by an independent gene locus (Koester et al., 1977; Holmes, 1977; Tashian et al., 1980a, b). The concentrations of the CA I and CA II isozymes are high in red blood cells (RBC) of most mammals; indeed, the concentration of carbonic anhydrase appears to be second only to that of hemoglobin in RBC (see Tashian and Carter, 1976). Polymorphism in carbonic anhydrase I I of rhesus monkeys ( M a c a c a m u l a t t a ) has been known for over a decade (Tashian, 1965; Tashian et al., 1968, 1971). The variation has been assumed to be controlled by autosomal codominant alleles. This assumption was based primarily on population data, but has been supported by limited data from pedigreed families (Tashian et al., 1971; Smith, 1980). Here we present extensive pedigree data which unequivocally demonstrate that the carbonic anhydrase I I phenotypes are

Genetic control of human apolipoprotein E polymorphism: Comparison of one-and two-dimensional techniques of isoprotein analysis

Genetic polymorphism of human apolipoprotein E (apo E) has previously been demonstrated by one-dimensional isoelectric focusing (Utermann et al. 1977b) and by two-dimensional electrophoresis of apolipoproteins (Zannis et al. 1981), but the relationship between the results obtained by these methods remained unclear. We therefore performed comparative phenotyping by one-dimensional and two-dimensional electrophoresis. Apoproteins from very low-density lipoproteins (apo VLDL) prepared by ultracentrifugation or from an apo Erich lipoprotein fraction prepared by heparin/Mg++ precipitation, were used as a source of apo E. Six common phenotypes designated apo E-4/4, apo E-N/N, apo E-D/D, apo E-4/N, apo E-4/D, and apo E-N/D were differentiated irrespective of the technique used or the source of apolipoproteins, but the two-dimensional electrophoresis of apo VLDL and apo VLDL which had been treated with neuraminidase was the key for the correct genetic interpretation of those phenotypes exhibiting the E4 isoform of the protein. Each phenotype is characterized by the presence of either one or two of three major isoforms E2, E3, and E4 and by the presence of several minor sialylated forms of these proteins (apo Es) that have higher apparent molecular weights. The unsialylated major isoform apo E2 does not only differ in charge but also has a higher apparent mol.wt. (about 34,500) than the major isoforms apo E3 and apo E4 (mol. wt. about 33,000). Family studies including 90 matings with a total of 203 offspring confirmed the genetic one locus model of Zannis et al. (1981). Apo E phenotypes are controlled by three autosomal codominant alleles apo Ed, apo En, and apo E4 that specify for the E2, E3, and E4 isoforms respectively. Phenotypes apo E-D/D,-N/N, and-4/4 represent homozygotes and phenotypes apo E-4/N,-4/D, and-N/D heterozygotes for these alleles.

Inheritance of allozymes in Atlantic herring (Clupea harengus harengus).

Progeny from single pair crosses of Atlantic herring were examined to determine the heritability of genetic variation at seven polymorphic allozyme loci. Mendelian inheritance of codominant autosomal alleles was established for IDH-2, LDH-1, LDH-2, ME-2, PGM-1, and PGI-2. This demonstration of Mendelian inheritance is essential for accurate interpretation of allozymic variation among natural populations of this pelagic species.

Genetic analysis of human salivary alpha-amylase isozymes by isoelectric focusing.

The isozymes of human salivary alpha-amylase have been separated by thin-layer gel isoelectric focusing in a pH 4-8 gradient followed by a starch-iodine zymogram procedure. The normal isozyme pattern (N) consisted of five major isozymes together with a number of minor ones. In addition, seven variant isozyme phenotypes were also observed, which had a combined frequency of 11.7% in a random population of 368 individuals. Analysis of familial data is indicative of the inheritance of autosomal codominant alleles.

Familial lecithin-cholesterol acyltransferase: identification of heterozygotes with half-normal enzyme activity and mass.

Lecithin-cholesterol acyltransferase (LCAT) mass and activity was measured in Canadian kindred of Italian and Swedish descent with familial LCAT deficiency. Four subjects had LCAT mass of 5.21 +/- 0.87 micrograms/ml (mean +/- SD) and LCAT activity of 98.8 +/- 12.0 nmol/h/ml, well within their respective normal ranges. Five family members, including the parents, the maternal grandmother, and two of four siblings of the LCAT deficient subjects, had enzyme mass (2.85 +/- 0.32 micrograms/ml) and activity (50.8 +/- 6.3 nmol/h/ml) approximately one-half that of normal levels. These presumed heterozygotes had normal levels of apolipoproteins A-I, A-II, B and D. The two subjects with LCAT deficiency had no detectable LCAT mass (below 0.1 microgram/ml) or LCAT activity (below 0.76 nmol/h/ml), apolipoprotein A-I and D levels approximately 50% of normal, and apolipoproteins B and A-II levels only 30-35% of normal. LCAT deficiency in this family is determined by an autosomal recessive mode. Furthermore, LCAT levels and activity are determined by two autosomal codominant alleles, LCATn, the normal LCAT gene, and LCATd, the LCAT deficiency gene.

Gamma-Glutamyl cyclotransferase: a new genetic polymorphism in the mouse (Mus musculus) linked to Lyt-2.

Electrophoretically variant forms of gamma-glutamyl cyclotransferase have been identified in red cells of inbred mouse strains. Each inbred strain exhibited a major band of activity and a minor band that migrated more anodally. The polymorphism affects the migration of both the major and minor bands in a similar way. F1 hybrids between strains with fast forms (A/J) and strains with the slow forms (C57BL/6J) exhibited a four-banded pattern consistent with co-dominant inheritance. The patterns observed in backcross and F2 mice were consistent with the segregation of a pair of autosomal co-dominant alleles. Recombinant inbred strains and a congenic strain were used to show that the locus controlling gamma-glutamyl cyclotransferase (Ggc) is linked to Lyt-2, a lymphocyte alloantigen locus on chromosome 6, with an estimated map distance of 5.0 +/- 2.5 centimorgans.

Phosphohexose isomerase polymorphism in the domestic cat.

Genetic variation of the enzyme phosphohexose isomerase (PHI) has been found in the erythrocytes of Australian domestic cats by horizontal starch gel electrophoresis at pH 8.2. Three complex patterns of isoenzymes, designated F, FS and S, were obtained migrating anodally. Limited family studies and the distribution of the three main phenotypes indicated that the polymorphism in controlled by two codominant autosomal alleles, PHIF and PHIS. Gene frequencies for PHIF and PHIS have been calculated as 0.036 and 0.964 respectively. Three additional variant forms have also been observed.

Studies on blood groups in the Japanese quail: the common antigens possessed by red blood cells and leukocytes, and their inheritance.

Two alloantigens, Ly1 and Ly2, were detected with alloantisera made by immunization with leukocytes. These antigens were present on red blood cells, peripheral leukocytes and spleen cells and found to be controlled by the autosomal codominant alleles. The phenotypic frequencies of Ly1 antigen in the three quail stocks, 1, 2, and 3, were 6.7, 0, and 100 percent, respectively, and those of Ly2 antigen were 0 percent in stocks 1 and 2, 7.1 percent in stock 3. It was suggested that Ly1 and Ly2 antigens might be associated with the system controlling A (QN1) antigen which was originally detected by the natural alloantibody. However, it remains to be investigated whether these antigens are associated with the major histocompatibility complex (MHC) of the Japanese quail.