[The challenge of science at the outset of the third millenium].

Compared to others species Homo sapiens is physically underprivileged as much by his relative weakness than by his lack of natural defense. Only his mental abilities allowed him to cope with the various dangers which threaten him and to rule over the biosphere that he managed to modified for his own benefit. The neolithic revolution which saw the generalization of agriculture and the breeding of animals offered a considerable quantities of resources which lead to a strong demographic growth.

Monoclonal antibodies directed against human Rh antigens in tests with red cells of non-human primates.

Human anti-D (Rho) monoclonal antibodies (Mabs) of the IgG (70) and IgM (27) classes were tested with red blood cells (RBCs) of various non-human primates, from anthropoid apes to New World monkeys. Significant differences in reactivity were observed among antibodies of two classes depending on taxonomic position of primate animals. Only IgM Mabs gave positive reactions (9 out of 18 Mabs) with blood of Old World monkeys.

Structural analysis of the RH-like blood group gene products in nonhuman primates.

Rh-related transcripts present in bone marrow samples from several species of nonhuman primates (chimpanzee, gorilla, gibbon, crab-eating macaque) have been amplified by RT-polymerase chain reaction using primers deduced from the sequence of human RH genes. Nucleotide sequence analysis of the nonhuman transcripts revealed a high degree of similarity to human blood group Rh sequences, suggesting a great conservation of the RH genes throughout evolution. Full-length transcripts, potentially encoding 417 amino acid long proteins homologous to Rh polypeptides, were characterized, as well as mRNA isoforms which harbored nucleotide deletions or insertions and potentially encode truncated proteins.

Length polymorphism of a microsatellite in human and non human primates.

Microsatellites are tandem repeats of short sequences elements (most often CA repeats) interspersed in many genomes and which frequently show multiallele polymorphism. They have proved invaluable for genomic mapping in man and other species and may be used for evolutionary studies provided that the available primers can be used in different species. The dystrophin gene, which shows high sequence conservation between man, rodents and chicken contains such polymorphic CA repeats.

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.

Comparative study of human monoclonal anti-D antibodies of IgG and IgM classes in tests with red cells of nonhuman primates.

Forty-nine human anti-D (Rho) monoclonal antibodies of the IgG and IgM classes were tested with red blood cells of various nonhuman primates, from anthropoid apes to Prosimians, and significant differences in reactivity were observed among antibodies of two classes depending on taxonomic position of primate animals. By and large, higher percentage of IgM mAbs gave positive reactions with nonhuman primate red cells and, particularly, with blood of lower monkeys: Old and New Worlds monkeys and Prosimians, than did those of IgG class. Allotypic reactions with red cells of African apes were produced by majority of IgG mAbs but by very few IgM reagents.

Y-chromosome-specific haplotype diversity in Ashkenazic and Sephardic Jews.

DNA samples from Ashkenazic and Sephardic Jews were studied with Y-chromosome-specific DNA probes p49f and p49a to screen for RFLPs and haplotypes. All 16 European haplotypes were found in Jews, but only 2 of them (VII and VIII) were widespread. Haplotype distributions in the two Jewish populations are similar, but haplotypes XI and XV are more frequent in the Ashkenazim and haplotypes IV and V are more frequent in the Sephardim, indicating their origins.

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.

Human monoclonal anti-D-induced clearance of human D-positive red cells in a chimpanzee model.

Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3.

Immunoglobulin Gm allotypes in apes: comparison with man.

Serum samples from 245 apes (184 Pan troglodytes, five Pan paniscus, 28 Gorilla gorilla, 23 Pongo pygmaeus abelei, and five Pongo pygmaeus pygmaeus) were tested for G1m (1,2,3,17), G2m (23), and G3m (5,6,10,11,13,14,15,16,21,24,28) immunoglobulin allotypes by the classical method of inhibition of hemagglutination. Some phenotypes are species specific while a few are shared by man and African apes.

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

The antigenic closeness between the chimpanzee alloantigen Rc of the R-C-E-F system, and the human alloantigen Rho(D) suggests a phyloge-connection 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.

Quantitative study of chimpanzee and gorilla counterparts of the human D antigen.

The reactivities of three human anti-D monoclonal antibodies (mAbs) with human, chimpanzee, and gorilla red blood cells (RBCs) were compared by quantitative radioimmunology and indirect immunofluorescence methods. The number of antigenic sites varies widely in gorillas (from 48,000-283,000), while in chimpanzees this number is very close to that observed in human R1R2 RBCs. The affinity of the anti-D antibodies was slightly lower with ape RBCs than with D-positive human RBCs.

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 Rc constitutes the crucial link with human Rh since the reactions of some chimpanzee alloimmune anti-Rc sera with human red cells parallel those obtained with human anti-Rho reagents. Reciprocally, properly absorbed human anti-Rho sera detect Rc specificity on chimpanzee red cells.

Survival of human monoclonal anti-Rho (D) antibodies in the rhesus monkey.

In vivo half-life of a 125I-labeled human anti-D monoclonal antibody (mAb) and that of 131I-labeled Rho-GAM was assessed in a rhesus monkey injected simultaneously with both reagents. The half-life of the mAb was 7.9 days, compared to 17 days of Rho-GAM.

[DNA polymorphism in a Brazilian population: relationship to allele frequencies in France].

The allele frequency distribution of two highly polymorphic DNA sequences was determined in a population from the metropolitan area of Fortaleza (Northeast Brazil). DNAs from 234 individuals were digested with Pvull and successively hybridized to each probe: alpha-Globin 3'HVR and Mucin HVR. The resulting allele frequencies were compared to those observed in a French population.

Relationships between consanguinity and migration rate from surname distributions and isonymy in France.

The distribution of surnames in France during the period 1916-40 is analysed from the civil birth registers for each of the 36,500 administrative units. The migration rate estimated from surnames is compared with the migration rate obtained from demographic census data. The correlations calculated among the 90 Departments ranges between 0.

Diversity of human anti-D monoclonal antibodies revealed by reactions with chimpanzee red blood cells.

Fifty-three human anti-D monoclonal antibodies (mAbs) revealed a striking diversity of reactions in tests with panels of chimpanzee red blood cells (RBCs) of various R-C-E-F blood group phenotypes (counterparts of the human Rh-Hr groups). The reactivities of these antibodies, which depended on the agglutination technique used, could be classified into four main types. These patterns of reactivity of anti-D mAbs with chimpanzee RBCs showed only limited correlation with types of reactions observed with human D variant RBCs.

[Study of equivalents of rhesus antigens in non-human primates].

Human alloantibodies specific of some Rh antigens cross-react with non human primates red blood cells. These crossreactions demonstrated that only African apes express equivalents of Rho (D) and hr' (c). The antigenic resemblance between these two human antigens and their primate homologues is confirmed by the reactivities of human anti-D and anti-c monoclonal antibodies.

[DNA polymorphism: comparison of allelic frequencies obtained with two HVR probes in a population from Northeastern Brazil and in two other ethnic groups].

DNAS from 325 individuals representing 2 different populations (234 Brazilians and 91 Asiatics) were analysed for Restriction Fragment Length Polymorphisms (RFLPs). These DNAs were digested with Pvu II enzyme and successively hybridized to two HVR probes: alpha globin-3'HVR and Mucin-HVR. An allele frequency distribution was determined for each couple probe/enzyme and each ethnic groupe studied.

The p49/TaqI Y-specific polymorphisms in three groups of Indians.

The TaqI/p49 Y-specific RFLPs were studied in 98 Indians coming from 3 locations in the country. A new allele (G0) and five new haplotypes (XX-XXIV) were found, not present in Caucasians and in Africans. In the genealogy of haplotypes, the new Indian haplotypes appear grouped together, and all Indian haplotypes occupy an intermediate position between Caucasian and African haplotypes.

Monoclonal antibodies directed against human Rh antigens in tests with the red cells of nonhuman primates.

Monoclonal antibodies against Rh related antigens on human red cells often crossreact with the red cells of the highest subhuman primate species. Depending on specificity of antibody, the species tested, and technique used, these reactions can be either species-specific or type specific. In tests with chimpanzee red cells, some of the latter type reactions have specificities related to the R antigen of the R-C-E-F blood group system of chimpanzee; specificities of some others seem to be unrelated to any known chimpanzee blood groups.

RH polymorphism in the Senegalese population.

RH polymorphism was evaluated in Senegalese ethnic groups: Ouolof, Serere, Toucouleur, Peul, Diola and Mande. The cDe frequency was high, the cde frequency varied between groups and the cDE frequency was twice as high as the CDe frequency. No significant heterogeneity could be assessed between tribes.

[Significance of alanine aminotransferase and reduction of post-transfusion non-A, non-B hepatitis].

To appreciate the test based on the activity of sera alanine aminotransferase (ALT) in the reduction of non-A non-B post-transfusional hepatitis, a study of the variation of this enzyme's activity was done versus several parameters: sex, age and acquired diseases. The population which included 25,813 Parisian blood donors (41.2% of men and 58.

Complexity of the Rh antigen demonstrated by comparative tests using antisera of human and primate origins.

Comparative analysis of two antisera, one produced in chimpanzee and another of human origin, demonstrates the existence of the whole spectrum of antibodies directed against at least four, and possibly five, antigenic determinants connected with the Rh reactivity. Some of the determinants are shared by chimpanzee and human red cells, while others are restricted to one species only. Based on this study, it is suggested that both the human Rh(D)-positive type and its chimpanzee counterpart, the Rc-positive type, could be of common origin, while the negative types are the results of later, parallel events during the evolution.