Autosomal Codominant Alleles Research Articles

A new genetically determined plasma protein polymorphism in the laboratory rabbit.

Two-dimensional agarose (pH 5.4)-polyacrylamide (pH 9.0) gel electrophoretic analysis of rabbit plasma proteins, followed by protein staining with Coomassie Brilliant Blue G250, revealed genetic polymorphism of a new, unidentified protein in the post-albumin region. This protein was tentatively designated as post-albumin with locus symbol Pa. Family data supported the hypothesis that the three different Pa phenotypes observed were controlled by two codominant autosomal alleles at a single locus. Each of the Pa homozygous types showed one fraction while the Pa heterozygous type had a pair of fractions. The Pa protein did not show activity to be ceruloplasmin, esterase, hemopexin, haptoglobin or protease (trypsin and chymotrypsin) inhibitor and it was also not likely to be the vitamin D-binding globulin (Gc protein). Pa polymorphism was observed in both of the breeds (New Zealand White and White of Dendermonde) studied.

Genetic and structural polymorphism of complement receptor 1 in normal Indian subjects

The human complement receptor 1 (C3b/C4b receptor, CD35, CR1), a polymorphic membrane bound glycoprotein, is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have suggested the functional and physiological significance of the structural (CR1-A/190, CR1-B/220, CR1-C/160 and CR1-D/250 kDa) and genomic (HH, high erythrocyte CR1 expression, HL, intermediate and LL, low expression) polymorphisms in health and disease. However, simultaneous study on the structural and genomic polymorphism in the same group of study subjects is lacking. This is the first study on both quantitative and structural polymorphism in 101 healthy volunteers from different parts of India by random sampling. In our study, AA phenotype was found to be expressed in 84.2% of individuals and 14.8% carried AB phenotype. One individual (0.9%) was found to possess BB phenotype. Homozygous BB pattern was identified for the first time in Indian subjects. The relative gene frequencies for A and B allele were found to be 0.916 and 0.084, respectively. Pertaining to quantitative polymorphism, percentage distribution for HH, HL and LL phenotypes was found to be 23.7, 54.45 and 21.79%, respectively and the gene frequencies were 0.51 and 0.49 for H and L allele, respectively. The observations for quantitative as well as structural polymorphism showed a good probability of fitness with Hardy–Weinberg equilibrium, thus proving that both the types of CR1 polymorphic forms are encoded by autosomal co-dominant alleles. We found a higher frequency of HL and AA phenotypes in the study subjects. Our findings are unique as we found that gene frequencies for structural and quantitative polymorphism in our study subjects were a combination of those found in Caucasian and Oriental populations.

Genetic polymorphisms of orosomucoid on the Han population in Nanjing of China

Human orosomucoid (ORM) is a major binding protein for various basic drugs. The genetic polymorphisms of ORM could be responsible for interindividual variation in the plasma binding of basic drugs, which might influence their effects or toxicities. The genetic polymorphisms of ORM on the Han population in Nanjing of China were analyzed by isoelectric focusing (IEF) on polyacrylamide gels following by immunoblotting. After desialylation of sera from 220 unrelated Chinese subjects, the band patterns of ORM showed that the polymorphism of the structural locus ORM1 is controlled by three codominant autosomal alleles, ORM1*F1, ORM1*F2 and ORM1*S, which presented five phenotypes, ORM1 F1, ORM1 S, ORM1 F1F2, ORM1 F1S, and ORM1 F2S. The allele frequencies were: ORM1*F1=0.7068, ORM1*F2=0.0182, ORM1*S=0.2750. The results presented in this paper indicate the ORM1 locus is polymorphic and the ORM2 locus is monomorphic in sera from the Han population in Nanjing of China.

Inheritance of 12 microsatellite loci in Oncorhynchus mykiss

Four full-sib families of Oncorhynchus mykiss were used to study the inheritance of allelic variation at 12 microsatellite loci. The loci examined were previously characterized in six different species from the family Salmonidae. Of the 48 genotypic ratios observed (12 loci x 4 crosses), disomic segregation of codominant autosomal alleles were established in 24 of 31 informative tests. The seven tests that did not conform to Mendelian ratios can be explained by the presence of null alleles (Oneμ14 and Omy77) and a locus (Oneμ1) that may be tandemly duplicated. Three significant pairwise linkage associations were observed between Oneμ1 and Omy207, Ssa85 and Oneμ11, and the two loci amplified by Oneμ1 primers, indicating these loci are not assorting independently. The presence of unexpected heteroduplex structures in Oneμ11 electropherograms in one cross prompted the sequencing of similar microsatellite electromorphs. Sequence differences revealed size homoplasy, that is, the electromorphs were identical in state but they were not identical by descent. These results demonstrate the need to conduct comprehensive species-specific inheritance studies for microsatellite loci used in population genetic or kinship analyses. Discovery of these four attributes by examining a small number of loci in four families suggests that they are common across microsatellite loci overall.

Phenotype 2 of deoxyribonuclease I may be used as a risk factor for gastric carcinoma.

Human deoxyribonuclease I (DNase I) (EC3.1.21.1) is one of the candidate nucleases that acts in mammalian cells during apoptosis. Genetic polymorphism of DNase I has been classified into 15 phenotypes controlled by 5 autosomal codominant alleles. The purpose of this study was to determine whether DNase I polymorphism is closely related to the incidence of gastric carcinoma. The phenotype distribution was examined using urine samples obtained from unrelated Japanese patients with gastric carcinoma (n = 97) and benign gastric diseases (n = 76). Phenotyping was performed using isoelectric focusing electrophoresis in thin polyacrylamide gel and immunoblotting with an antihuman DNase I antibody. A close statistical association was found between patients with gastric carcinoma and a high frequency of DNase I phenotype 2. However, there was no significant difference in the phenotype distribution between the group of patients with benign gastric diseases and the controls. The findings of the current study suggest that DNase I phenotype 2 may be a marker for gastric carcinoma. Therefore, compared with other phenotypes, DNase I phenotype 2 may have potential for identifying patients who are at risk of harboring or developing gastric carcinoma.

Plasma protease inhibitor (PI) system in the laboratory opossum, Monodelphis domestica.

Protease inhibitor (PI) polymorphism was observed in the laboratory opossum, Monodelphis domestica, by either one-dimensional acid polyacrylamide gel electrophoresis (PAGE; pH 4.6) or isoelectric focusing (pH 3.5-5.0) followed by immunoblotting with rabbit antiserum to human alpha 1-antitrypsin; but acid PAGE produced superior resolution of the PI proteins. Family studies demonstrated an inheritance of nine codominant autosomal alleles, PID, PIE, PIF, PIG, PIH, PII, PIJ, PIK, and PIM, and a population study revealed frequencies of 0.411, 0.010, 0.341, 0.034, 0.023, 0.071, 0.035, 0.020, and 0.055, respectively.

Linkage between the loci for serum albumin and vitamin D binding protein (GC) in the Japanese quail

SummaryVitamin D binding protein (GC) and serum protease inhibitor (PI) have been added to genetic markers in the Japanese quail. Both loci were controlled by autosomal codominant alleles named GCA, GCB and PIA, PIB, PIC, respectively. Close linkage between the loci for serum albumin (ALB) and GC protein is reported. Two recombinants were observed in 145 informative offspring of 14 families. The recombination frequency between the loci was estimated as 0.014±0.006. Thus, GC was assigned to linkage group II in the Japanese quail. No signs of linkage were observed among the loci for the ALB‐GC complex, PI. serum prealbumin 2 (PA2), phosphoglucose isomerase (PG1), 6‐phosphogluconate dehydrogenase (PGD) and esterase‐D (ESD).

Ethanol tolerance and variation at the alcohol dehydrogenase (Adh) locus of Drosophila mauritiana.

Drosophila mauritiana larvae are tolerant to ethanol as a supplementary nutritional resource at low concentrations. Higher levels of ethanol (5 per cent) in the food adversely affect larval behaviour causing reduced rates of locomotion and feeding which are associated with low larva-to-adult survival. Two codominant autosomal alleles AdhS and AdhF controlling variant electromorphs of alcohol dehydrogenase are indistinguishable in their effects on ethanol tolerance in this species. A comparison of larval behaviours shows that D. mauritiana has a lower ethanol tolerance than either of its sibling species D. melanogaster and D. simulans.

Characterization of apo(a) polymorphism by a modified immunoblotting technique in an italian population sample

Apo(a), the specific lipoprotein(a) (Lp(a)) apolipoprotein, is characterized by different isoforms (from 6 to 11 on SDS-PAGE) encoded by a system of autosomal codominant alleles. Electrophoresis on agarose gel displays a better resolving power than SDS-PAGE (a larger number of apo(a) isoforms is detected). The aim of this work was to set up a simple technique that uses a capillary blotting apparatus and a polyvinylidene difluoride membrane for protein transfer. We tested an Italian population sample of 202 healthy subjects (123 men and 79 women) and we detected 22 apo(a) isoforms varying from 280 to 775 kDa. In our sample, 135 subjects (66.5%) had a single-band phenotype, 64 (31.7%) had a double-band phenotype and 3 subjects (1.5%) had no detectable bands (‘null’ phenotype). This simple and reproducible technique could be applied in the genetic screening of apo(a) polymorphisms and for clinical investigations of the risk of developing cardiovascular diseases.

Polymorphism of transferrin found in the laboratory rat and wild rats in Japan.

Polymorphism of the transferrin locus (Tf) was found in the laboratory rat and wild rats in Japan by polyacrylamide gel electrophoresis. Two phenotypes, "a" and "b," were distinguished in homozygotes. It is suggested that these are controlled by autosomal codominant alleles. In 10 laboratory strains, only the IS strain showed the a type. This allele found in the IS strain was broadly distributed in Japanese wild rats. It is considered to be derived from a wild rat in Japan. Linkage relationship between Tf and Alp-1 was not established.

Antithrombin III (AT3) polymorphism in the marsupialMonodelphis domestica: Identification and genetics

Antithrombin III polymorphism was observed in the gray short-tailed opossum, Monodelphis domestica, by either one-dimensional polyacrylamide gel electrophoresis (PAGE; pH 7.9), two-dimensional PAGE (agarose, pH 5.4; 12% T, pH 7.9), or isoelectric focusing (pH 4.2-4.9) followed by immunoblotting with rabbit antiserum to human antithrombin III. Family studies demonstrated an inheritance of three codominant autosomal alleles, AT3A, AT3B, and AT3C, and a population study revealed frequencies of 0.70, 0.10, and 0.20, respectively.

A new transferrin allele in Australian goats.

Subdivision of TF B into two variants, B1 (faster) and B2 (slower) in Australian goat breeds was accomplished by high voltage, thin layer polyacrylamide gel electrophoresis at pH 7.9. The genes controlling the caprine transferrins were shown to be autosomal codominant alleles, TFA, TFB1, TFB2 and TFC and in the various breeds of goats, the alleles were in Hardy-Weinberg equilibrium. TFA was the most common allele in the Australian and Texan Angora, Cashmere and Dairy breeds with gene frequencies ranging from 0.652 to 0.977. TFB1 and TFB2 occurred in all four breeds while TFC was only observed in very low frequencies in Australian Angora and Cashmere breeds.

Genetic variation of human sex hormone-binding globulin: evidence for a worldwide bi-allelic gene.

Genetic variation of human sex hormone-binding globulin (SHBG) has been investigated on 1690 unrelated neuraminidase-treated serum samples using isoelectric focusing followed by transfer to nitrocellulose membranes and immunostaining. Three clearly distinct isoelectric focusing patterns, consistent with the expression of an autosomal genetic system, were identified. Using allele frequencies, calculated on the basis of a bi-allelic gene, an excellent agreement between observed and expected phenotype numbers was obtained in every examined population sample. Family data along with the observed distribution of the three SHBG phenotypes among racially different groups and sexes indicate that SHBG is worldwide encoded by two autosomal codominant alleles. Compared with healthy Belgian blood donors no statistically significant differences were noted for the allele frequencies among 399 patients and 70 hirsute women of Belgian origin. Evidence is also presented that the subunit produced by the variant allele (SHBG2) has a higher molecular mass than the one produced by the regular allele (SHBG1) and that the three SHBG genotypes have identical binding characteristics for 5 alpha-dihydrotestosterone.

Discovery of a genetic polymorphism of human plasma protein C inhibitor (PCI): genetic survey utilizing isoelectric focusing followed by immunoblotting, immunological and biochemical characterization.

The objectives of this study were to determine the genetic basis of the electrophoretic differences of human plasma protein C inhibitors (PCI) from 977 individuals. Three discrete antibodies were produced against the PCI purified from human plasma and peptides that corresponded to the N-terminal 15 amino acid residues and the C-terminal 15 residues of human PCI, the chemical structures of which were determined by cDNA sequence analysis. The combined techniques of polyacrylamide gel isoelectric focusing and immunoblotting with these three different antibodies resolved the plasma PCI into several isoprotein bands, with a pH range of 6-7. These PCI isoproteins, however, were not stained by anti-human kallikrein, anti-human protein C or anti-human urokinase antibodies. Therefore, each of the PCI bands, which were detected by immunoblotting with the anti-PCI antibody and the two different anti-peptide antibodies, were derived from free PCI, and not an inactive PCI species. Two common phenotypes, designated PCI 1 and 1-2, were recognized, and family studies showed that they represented homozygosity or heterozygosity for two autosomal codominant alleles, PCI*1 and PCI*2. A population study of plasma samples collected from 977 Japanese individuals indicated that the frequencies of the PCI*1 and PCI*2 alleles were 0.988 and 0.012, respectively.

Inheritance of allozymes in Atlantic salmon ( Salmo salar L.)

Progeny from single-pair matings of Atlantic salmon ( Salmo salar L.) were examined to determine the heritability of observed electrophoretic variation at seven polymorphic enzyme loci. Mendelian inheritance of codominant autosomal alleles was established for Aat-3, Idh-3, Mdh-3,4, m Me-2, Pgi-3 and Sdh-1,2 loci. Polymorphism observed at the Pgm-2 locus did not conform to any known genetic model. This determination of the genetic basis of several common polymorphisms enhances our ability to interpret observed allozyme variation in this species.

Biochemical and genetic studies on GP43, a 43-kD glycoprotein detected immunologically in human urine and serum.

A new and previously undescribed glycoprotein with a molecular weight of 43,000 has been isolated from human urine. This protein, designated GP43; copurified with ribonuclease, which has the same molecular weight, but ribonuclease activity was removed by passage through an affinity column of agarose-5'-(4-aminophenyl phosphoryl) uridine 2'(3') phosphate. GP43 contains about 5.9% neutral sugar, 2.3% hexosamine, and 1.6% sialic acid. A rabbit antibody to the purified GP43 reacted with human urine and serum as well as with the purified GP43. The genetic polymorphism of GP43 was then studied in desialylated human serum samples by urea-polyacrylamide gel isoelectric focusing, followed by immunoblotting with the specific antibody for GP43. Three common phenotypes, designated GP43 1, 1-2, and 2, were easily recognized using this technique and represented homozygosity or heterozygosity for two autosomal codominant alleles, GP43*1 and GP43/2. The frequencies of the GP43*1 and GP43*2 alleles in a Japanese population were 0.7683 and 0.2317, respectively.

Genetic analysis of CR1 (the C3b complement receptor, CD35) expression on erythrocytes of HIV-infected individuals

The number of C3b receptor (CR1) molecules on erythrocytes is genetically determined by two codominant autosomal alleles. The genetic polymorphism of CR1 expression correlates with a Hind III restriction fragment length polymorphism (RFLP) of the CR1 gene. The relative frequency of individuals homozygous for the allele coding for low CR1 numbers is approximately 5% of the normal population. CR1 numbers/erythrocytes are significantly decreased in symptomatic HIV-infected individuals. Decreased CR1 expression correlates with the severity of disease. The present study investigated the CR1 genomic Hind III RFLP-related polymorphism in 79 HIV-infected individuals and 84 healthy subjects. Allele frequencies were found to be similar in both populations. Thus, there is no susceptibility nor resistance to HIV-infected linked to the CR1 gene. Defective expression of CR1 in HIV-infected patients is acquired through central and/or peripheral mechanisms.

Two BF F subtypes, but no BF S, BF F1 or BF S07 subdivision, are found by isoelectric focusing.

When studied by immunoelectrophoresis the factor B (BF)*F allele is a monomorphic protein, but by using isoelectric focusing (IEF), it turns out to be polymorphic. Two BF*F allelic subdivisions, BF*FA and BF*FB, were detected in samples from unrelated Spanish donors; *FA and *FB are in Hardy-Weinberg equilibrium, segregate as autosomal codominant alleles in families, and BF*FA (but not BF*FB) is found to be in linkage disequilibrium with B44 and DR7 and is within the A29, B44, Bw4, Cx, CFA31, DR7, DRw53, DQ2 haplotype. Furthermore, BF FA individuals have a higher BF serum concentration than the BF FB individuals. The subdivision of BF S observed with IEF was found to be due to nonspecific BF S cleavage by serum proteases in inadequately collected or aged samples. Thus, the subdivision of BF S is spurious and was not found in our sera. BF F1 and BF S07 could not be further subdivided by IEF in our subjects. The BF F1 banding pattern was characterised by the presence of a cathodal band which corresponds to the Bb activation fragment. Finally, IEF combined with immunoblotting and monoclonal Ba and Bb antibodies may be used for accurately distinguishing BF phenotypes and doubtful bands.

Genetic polymorphism of human urine deoxyribonuclease I.

A genetic polymorphism of human urine deoxyribonuclease I (DNase I) has been detected by the technique of polyacrylamide gel isoelectric focusing (IEF-PAGE) followed by immunoblotting with anti-DNase I antibody. Family studies showed that the three common phenotypes - DNASE1 1, 1-2, and 2 - and the other four rare phenotypes - DNASE1 1-3, 2-3, 2-4, and 3-4 - represent homozygosity or heterozygosity for four autosomal codominant alleles, DNASE1*1, *2, *3, and *4. The frequencies of the DNASE1*1, DNASE1*2, DNASE1*3, and DNASE1*4 alleles in a studied Japanese population were 0.5453, 0.4396, 0.0117, and 0.0034, respectively.

Two BF F Subtypes, but no BF S, BF F1 or BF S07 Subdivision, Are Found by Isoelectric Focusing

When studied by immunoelectrophoresis the factor B (BF)*F allele is a monomorphic protein, but by using isoelectric focusing (IEF), it turns out to be polymorphic. Two BF*F allelic subdivisions, BF*FA and BF*FB, were detected in samples from unrelated Spanish donors; *FA and *FB are in Hardy-Weinberg equilibrium, segregate as autosomal codominant alleles in families, and BF*FA (but not BF*FB) is found to be in linkage disequilibrium with B44 and DR7 and is within the A29, B44, Bw4, Cx, CFA31, DR7, DRw53, DQ2 haplotype. Furthermore, BF FA individuals have a higher BF serum concentration than the BF FB individuals. The subdivision of BF S observed with IEF was found to be due to nonspecific BF S cleavage by serum proteases in inadequately collected or aged samples. Thus, the subdivision of BF S is spurious and was not found in our sera. BF F1 and BF S07 could not be further subdivided by IEF in our subjects. The BF F1 banding pattern was characterised by the presence of a cathodal band which corresponds to the Bb activation fragment. Finally, IEF combined with immunoblotting and monoclonal Ba and Bb antibodies may be used for accurately distinguishing BF phenotypes and doubtful bands.