Molecular genetics of chimpanzee Rh-related genes: Their relationship with the R-C-E-F blood group system,the chimpanzee counterpart of the human rhesus system

As the chimpanzee R-C-E-F blood group system appears to be the chimpanzee counterpart of the human Rhesus (RH) system, we have tried to determine whether chimpanzee Rh-like genes encode R-C-E-F-related proteins. Chimpanzee genomic DNA, digested by any of eight endonucleases and hybridized with three Rh exon-specific probes, exhibits a high degree of polymorphism. Analysis of DNA from unrelated individuals of different R-C-E-F types revealed that the presence of some restriction fragments is correlated with particular R-C-E-F types. The cosegregation of these fragments with R-C-E-F haplotypes was confirmed by family studies. Oligonucleotides complementary to regions flanking human exons were used as PCR primers on chimpanzee DNA; the resulting amplified fragments were identical in size to their human counterparts. Moreover, the nucleotide sequences of the fragments present a high degree of similarity to the corresponding human regions.     

The R-C-E-F blood group system of chimpanzees: Serology and genetics

Six chimpanzee alloimmune antibodies define 20 phenotypes of the R-C-E-F blood group system, the counterpart of the human Rh system. Of the several specificities of this system, the R^c constitutes the crucial link with human Rh since the reactions of some chimpanzee alloimmune anti-R^c sera with human red cells parallel those obtained with human anti-Rh_o reagents. Reciprocally, properly absorbed human anti-Rh_o sera detect R^c specificity on chimpanzee red cells. Tests with large panels of human monoclonal anti-D antibodies confirm the notion of shared epitopes between human alloantigen Rh_o(D) and chimpanzee alloantigen R^c.     

Relationship between chimpanzee Rh-like genes and the R-C-E-F blood group system

The antigenic closeness between the chimpanzee alloantigen R^c of the R-C-E-F system, and the human alloantigen Rh_o(D) suggests a phylogeconnection between their genes. To confirm at the molecular level the common origin of these genes, genomic DNA from 16 unrelated chimpanzees of various R-C-E-F phenotypes were digested by three restriction enzymes and analyzed by Southern blot using a human Rh cDNA probe and three exon-specific probes. Restrictions profiles displayed reach polymorphism. Correlations between some bands and certain R-C-E-F phenotypes demonstrate that the human Rh cDNA probe defines in chimpanzee genomic DNA some genes of the R-C-E-F system.     

The inheritance of blood groups in the blood group system B in cattle

The mode of inheritance of blood groups in man and animals has been a matter of discussion as long as investigations in this field have been performed.A series of aberrations from the usual transmission of genes controlling the blood groups of the system B of cattle is presented. These data offer a contribution to the assumption that the blood groups are controlled by linked genes.On leave from the Faculty of Agriculture, University of Cairo, Egypt, U.A.R.     

Canine blood groups. 2. Description of a new allele in the Tr blood group system

A previously unrecognized canine red cell antigen, tentatively named O, was found after absorption analysis of an alloimmune antiserum and absorption of several immune or naturally occurring cross-reacting heteroantibodies from man, cattle and swine. The serological results and genetic analysis of a limited number of complete dog families indicated that the new factor probably belongs to the Tr blood group system. No individual possessed both factors Tr and O, and a large proportion of animals was negative for both factors. The serological pattern for the new Tr system obtained was consistent with similar systems observed in sheep (A-O), pig (R-O) and man (Bombay) in which the gene for one factor was dominant over and masked the gene for the second factor in the system. The negative phenotype was accounted for by the actions of an epistatic gene.     

Evolutionary genetics of the human Rh blood group system

The evolutionary history of variation in the human Rh blood group system, determined by variants in the RHD and RHCE genes, has long been an unresolved puzzle in human genetics. Prior to medical treatments and interventions developed in the last century, the D-positive (RhD positive) children of D-negative (RhD negative) women were at risk for hemolytic disease of the newborn, if the mother produced anti-D antibodies following sensitization to the blood of a previous D-positive child. Given the deleterious fitness consequences of this disease, the appreciable frequencies in European populations of the responsible RHD gene deletion variant (for example, 0.43 in our study) seem surprising. In this study, we used new molecular and genomic data generated from four HapMap population samples to test the idea that positive selection for an as-of-yet unknown fitness benefit of the RHD deletion may have offset the otherwise negative fitness effects of hemolytic disease of the newborn. We found no evidence that positive natural selection affected the frequency of the RHD deletion. Thus, the initial rise to intermediate frequency of the RHD deletion in European populations may simply be explained by genetic drift/founder effect, or by an older or more complex sweep that we are insufficiently powered to detect. However, our simulations recapitulate previous findings that selection on the RHD deletion is frequency dependent and weak or absent near 0.5. Therefore, once such a frequency was achieved, it could have been maintained by a relatively small amount of genetic drift. We unexpectedly observed evidence for positive selection on the C allele of RHCE in non-African populations (on chromosomes with intact copies of the RHD gene) in the form of an unusually high F( ST ) value and the high frequency of a single haplotype carrying the C allele. RhCE function is not well understood, but the C/c antigenic variant is clinically relevant and can result in hemolytic disease of the newborn, albeit much less commonly and severely than that related to the D-negative blood type. Therefore, the potential fitness benefits of the RHCE C allele are currently unknown but merit further exploration.     

Application of maximum likelihood statistics for the population and family studies of inheritance of the chimpanzee R-C-E-F and V-A-B-D blood groups

Maximum likelihood statistics were applied to the analysis of serological data to confirm the originally proposed genetic models of the chimpanzee R-C-E-F and V-A-B-D systems. Five hundred ninety-nine chimpanzees, including 81 parents of 114 offspring, were tested for R-C-E-F, and 60 parents of 80 offspring were tested for V-A-B-D blood groups. An estimation-maximization procedure was used to obtain maximum likelihood estimates and support intervals of the haplotype frequencies. For each haplotype, the null hypothesis of nonexistence was evaluated. The frequencies obtained by this method do not differ significantly from those calculated by the square root formula, but put these estimates on a statistically more rigorous footing.     

Molecular characterization of the human ABO blood group orthologus system in pigs

The selection and use of animals with blood group 0 in the process of transplanting pig organs or tissues into humans can positively contribute to the control of acute immune rejection due to differences in blood groups. Exon-specific PCRs for the porcine blood group A transferase gene against genomic DNA from either blood group A or 0 animals resulted in the amplification failure of the A0 blood group gene exon 8 from blood group 0 animals. To characterize the genetic abnormality in the genome of blood group 0 animals, we screened bacterial artificial chromosome (BAC) clones from a Korean native pig BAC library which had the blood group 0 allele, and carried out shotgun sequencing. The analysis showed that the 0 allele has a large deletion between exon 7 of the A0 blood group gene and the neighbouring SURF6. We also showed that the ABO blood group antigens in humans and the A0 blood group antigens in pigs are coded by mutations within the orthologous glycosyltransferase gene. In addition, we developed a multiplex genotyping method for the porcine A0 blood group gene.     

Detection of four human milk groups with respect to Lewis blood group dependent oligosaccharides

Neutral oligosaccharides in human milk samples from approximately 50 women were analysed applying a recently developed high-pH anion-exchange chromatographic method. Three different oligosaccharide patterns could be detected in accordance with milk groups that had been already described. These oligosaccharide groups correspond to the Lewis blood types Le(a−b+), Le(a+b−) and Le(a−b−). In addition to these oligosaccharide patterns, a new carbohydrate pattern was detected in a milk sample from a Le(a−b−) individual. Here, only nonfucosylated oligosaccharides and compounds bearing a1,3 linked fucosyl residues were found, whereas structures with a1,2 and a1,4 fucosyl linkages were missing. This finding led to the hypothesis that there are four different oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood group system. This revised version was published online in November 2006 with corrections to the Cover Date.     

ABO blood group system

The accuracy of regular serum methods to detect ABO blood groups can be negatively affected by some factors, such as irregular antibodies, autoantibodies or effects of diseases leading to false or weak agglutination. This study aimed to accurately identify ambiguous ABO blood groups by serological and gene detection methods. The samples were collected in the First Affiliated Hospital of Nanjing Medical University from December 2018 to December 2019. ABO genotyping was performed by polymerase chain reaction-sequence specific primer (PCR-SSP) method in 20 samples, and ABO exons 6 and 7 or FUT1 and FUT2 genes were sequenced in 5 samples. The genes detected in the 21 specimens included 4 cases of A/B, 2 cases of A205/O01, 3 cases of A/O01, 3 cases of A/O02, 1 case of O01/O01, 1 case of O01/O02, 1 case of B/O01, 1 case of B/O02, 1 case of Bel/O01, 1 case of Cisab01/O01, 1 case of rare B/O04, 1 case of Bombay-like Bmh, 1 case of new gene showing c.261del G of exon 6, c.579 T > C of exon 7 and B new/O01. This study suggests that ABO blood group genotyping technology combined with serological typing can be used for accurately typing ambiguous blood groups.     

ABO blood group system

The ABO blood group system in humans has three different carbohydrate antigens named A, B, and O. The A antigen sequence is terminal trisaccharide N-acetylgalactosamine (GalNAc)α1-3[Fucα1-2]Galβ-, B is terminal trisaccharide Galα1-3[Fucα1-2]Galβ-, and O is terminal disaccharide Fucα1-2Galβ-. The single ABO gene locus has three alleles types A, B and O. The A and B genes code A and B glycosyltransferases respectively and O encodes an inactive enzyme. A large allelic diversity has been found for A and B transferases resulting in the genetic subgrouping of each ABO blood type. Genes for both transferases have been cloned and the 3D structure of enzymes with and without substrate has been revealed by NMR and X ray crystallography. The ABO blood group system plays a vital role in transfusion, organ and tissue transplantation, as well as in cellular or molecular therapies.     

ABO blood group system

The ABO blood group system in humans has three different carbohydrate antigens named A, B, and O. The A antigen sequence is terminal trisaccharide N-acetylgalactosamine (GalNAc)α1-3[Fucα1-2]Galβ-, B is terminal trisaccharide Galα1-3[Fucα1-2]Galβ-, and O is terminal disaccharide Fucα1-2Galβ-. The single ABO gene locus has three alleles types A, B and O. The A and B genes code A and B glycosyltransferases respectively and O encodes an inactive enzyme. A large allelic diversity has been found for A and B transferases resulting in the genetic subgrouping of each ABO blood type. Genes for both transferases have been cloned and the 3D structure of enzymes with and without substrate has been revealed by NMR and X ray crystallography. The ABO blood group system plays a vital role in transfusion, organ and tissue transplantation, as well as in cellular or molecular therapies.     

Natural antibodies and immune antibodies of human ABO blood group system

Sera of normal and isoimmunized persons genotype OO and A₁O were fractionated to separate the three main immunoglobulin components IgG, IgM and IgA from each other. The anti-B activity was measured in every fraction and individual serum. The results indicate that the natural anti-B antibodies are of IgM molecular type, contrasting with the immune anti-B antibodies which are IgM, IgG and eventually IgA. The restriction to the IgM class and other data previously reported are discussed in relation to the origin of the natural antibodies of the human ABO blood group system.