RESUMEN
Ten population samples from different geographic origins were tested serologically for the AG polymorphism of human beta-lipoproteins. Their haplotype frequencies were used with previously published data to perform a wide analysis of AG genetic differentiations throughout the world. Coancestry coefficients were computed from weighted F(ST)s among populations by using a matrix of molecular distances among AG haplotypes, which is here determined on the basis of DNA studies. Coancestry coefficients derived from unweighted F(ST)s and more classical Prevosti distances were computed on the same data and used for a comparison. In all cases a highly significant correlation was found between genetics and geography on a worldwide scale, while the significance of the correlation with linguistics differed. A test of significance of the pairwise F(ST)s among populations also gave different results depending on whether the molecular distance matrix among AG haplotypes was included. Globally, this study shows that in spite of being highly significantly correlated to each other, different genetic distance measures can lead to different interpretations of the same data set. Moreover, the elucidation of the molecular models related to the presently known serological polymorphisms may represent an additional tool for analyzing such polymorphisms in human population genetics studies.
Asunto(s)
Apolipoproteínas B/genética , Epítopos/genética , Etnicidad/genética , Variación Genética/genética , Alotipos de Inmunoglobulinas/genética , Polimorfismo Genético/genética , Sustitución de Aminoácidos/genética , Apolipoproteína B-100 , Etnicidad/estadística & datos numéricos , Frecuencia de los Genes/genética , Genotipo , Haplotipos/genética , Humanos , Lenguaje , Lingüística , Modelos Genéticos , Biología Molecular , Mapeo Nucleótido , Polimorfismo de Longitud del Fragmento de Restricción , Características de la Residencia/estadística & datos numéricos , Pruebas SerológicasRESUMEN
We present the results of AG antigen typings of three Caucasoid population samples: Lebanese, Tunisians, and Finns. AG haplotype frequencies estimated by maximum-likelihood methods are compared with the frequencies observed in 13 world populations previously tested for AG specificities by computing a genetic distance matrix used in a multivariate analysis. A high degree of polymorphism characterizes the three samples, with 10 haplotypes detected in the Lebanese and 11 haplotypes detected in the Tunisians and Finns; high heterozygosity levels are also present in the three populations. The genetic distance analysis shows that the three populations possess a genetic structure intermediate between those observed in sub-Saharan Africans and in Caucasoids from the Near East and India. This tight correspondence between AG differentiation and geography is confirmed by a highly significant correlation coefficient found between genetic and geographic distances computed worldwide, suggesting that an isolation by distance model of evolution applies to the AG system. The Ewens-Watterson test for selective neutrality on all world populations tested for AG specificities also supports the hypothesis that the AG system behaves like a neutral polymorphism. Overall, the AG differentiation pattern appears to be close to the patterns observed for other serological polymorphisms, such as RH, GM, and HLA, whose evolutionary mechanisms are also discussed.
Asunto(s)
Antígenos de Diferenciación/genética , Apolipoproteínas B/genética , Frecuencia de los Genes/genética , Haplotipos/genética , Polimorfismo Genético/genética , Población Blanca/genética , Apolipoproteína B-100 , Finlandia , Tamización de Portadores Genéticos , Humanos , Líbano , Funciones de Verosimilitud , Análisis Multivariante , Fenotipo , Filogenia , Muestreo , TúnezRESUMEN
Since 1986 the factor VIII and IX concentrates of the Central Laboratory, Swiss Red Cross Blood Transfusion Service have been virus inactivated with tri-(n-butyl) phosphate and Tween 80. Clinical studies had shown that both preparations were well tolerated and hemostatically effective; no HIV infection was transmitted. However, safety from transmission of non-A/non-B hepatitis could not be shown since the study included no previously untreated patients. In the meantime, a laboratory test has become available which allows retrospective testing for anti-hepatitis C antibodies in frozen sera of the study patients. 5 of the 26 patients, observed during a 2-year follow-up study, had no HCV antibodies before entering the long-term trial. During this trial, each of these 5 patients substituted an average quantity of 40,200 coagulation factor units (7500-69,000) from 45 production lots. None of these 5 patients developed anti-HCV antibodies, nor did any of them show clinical signs of infection with hepatitis. This suggests that virus inactivation using solvent/detergent treatment reduces the risk of transmission of HCV.
Asunto(s)
Trastornos de la Coagulación Sanguínea/terapia , Transfusión Sanguínea , Hepacivirus/efectos de los fármacos , Hepatitis C/transmisión , Trastornos de la Coagulación Sanguínea/inmunología , Hepacivirus/inmunología , Anticuerpos Antihepatitis/aislamiento & purificación , Hepatitis C/prevención & control , Humanos , Organofosfatos/farmacología , Polisorbatos/farmacologíaRESUMEN
The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes.
Asunto(s)
Apolipoproteínas B/genética , Evolución Biológica , Haplotipos , Hominidae/genética , África/etnología , Secuencia de Aminoácidos , Animales , Asia/etnología , Australia/etnología , Secuencia de Bases , Etnicidad , Europa (Continente)/etnología , Frecuencia de los Genes , Variación Genética , Gorilla gorilla/genética , Humanos , Datos de Secuencia Molecular , Pan troglodytes/genética , Polimorfismo Genético , Grupos Raciales , Homología de Secuencia de Ácido NucleicoRESUMEN
The significance of indeterminate screening antibody test for human immunodeficiency virus (HIV) serology is still difficult to evaluate, especially in low-risk populations. One hundred twenty-seven blood donors with an initially reactive screening test for HIV antibodies were enrolled in this study. The sera of 95 of these blood donors were reactive on repetition of the test, and none had detectable circulating p24 antigen. Western blot (WB) analysis of the repeatedly reactive sera was as follows: 9 positive, 31 indeterminate, and 55 negative. One of the blood donors with indeterminate WB later presented a seroconversion. On subsequent control 3 to 12 months later, the sera from donors with indeterminate or negative WB did not present any parameters that may indicate a seroconversion. DNA was purified from citrated blood collected from the 127 blood donors at the time of the initial antibody screening. Five micrograms of each DNA sample corresponding to 7 x 10(5) nucleated white blood cells was amplified by polymerase chain reaction (PCR) in the presence of oligonucleotides (primers) corresponding to a highly conserved segment of the pol gene. The detection of amplified DNA was achieved by dot blot and Southern blot using appropriate 32P-labeled oligonucleotides. Ten DNA samples were positive, 9 corresponded to blood donors with a positive HIV serology, and 1 to the blood donor who later presented a seroconversion. These results confirm the sensitivity of the PCR for the diagnosis of HIV infection; they also suggest that repetition of the serology at 3- to 12-month intervals is a valuable procedure for the control of HIV infection status in blood donors.
Asunto(s)
ADN Viral/genética , Amplificación de Genes/genética , Seropositividad para VIH/genética , VIH-1/genética , Secuencia de Bases , Donantes de Sangre , Sondas de ADN , Genes pol/genética , Humanos , Técnicas para Inmunoenzimas , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Reacción en Cadena de la PolimerasaRESUMEN
The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of the most recent genetic polymorphism studies.
Asunto(s)
Antígenos/genética , Genética de Población , Haplotipos , Lipoproteínas LDL/genética , Polimorfismo Genético , Apolipoproteínas B/genética , Apolipoproteínas B/inmunología , Epítopos/genética , Frecuencia de los Genes , Humanos , Lipoproteínas LDL/inmunología , Fenotipo , Grupos Raciales/genéticaRESUMEN
Human low density lipoprotein shows a genetic polymorphism, the so-called Ag-system. it consists of 5 pairs of allelic epitopes, x/y, al/d, c/g, t/z, and h/i, which are localized on apolipoprotein B. We have generated a large number of monoclonal antibodies against low density lipoprotein. Two of them, D2E1 and H11G3, recognize epitopes related to this genetic polymorphism. Direct ELISA and ELISA inhibition experiments with different low density lipoproteins of known phenotype showed that D2E1 is directed against the allelic epitope c and H11G3 against d. The two antibodies were used for the characterization of low density lipoprotein in sera from different blood donors and the results compared to those obtained by passive hemagglutination using human allotypic anti-sera. Sera from homo- or heterozygous donors (which display the relevant epitope) could be distinguished from the sera of homozygous donors (which lack the epitope) with the monoclonal antibodies described.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Lipoproteínas LDL/inmunología , Alelos , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Apolipoproteínas B/genética , Apolipoproteínas B/inmunología , Unión Competitiva , Ensayo de Inmunoadsorción Enzimática , Epítopos/genética , Epítopos/inmunología , Variación Genética , Humanos , Lipoproteínas LDL/genética , Fenotipo , Polimorfismo GenéticoRESUMEN
A monoclonal antibody (BIP 45) against human apolipoprotein B (apo B) was used to study the polymorphism of apo B in families and in unrelated subjects. BIP 45 bound to apo B-containing lipoprotein particles in one of three distinct patterns of immunoreactivity (strong, weak and intermediate). Family studies showed that these binding patterns result from co-dominant transmission of apo B allelic pairs which are temporarily designated allele BIP- and allele BIP+; allele BIP+ would code for the apo B BIP 45 epitope. Analysis of plasma samples from 244 unrelated men randomly chosen from the North French population indicated that 46.7% of them bound BIP 45 with low affinity (weak reactors), 44.7% with intermediate affinity (intermediate reactors) and 8.6% with high affinity (strong reactors). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.690/0.310 for the type BIP-/BIP+ alleles. This corresponds to the gene frequencies of 0.695/0.305 at the Ag(g)/Ag(c) locus previously found in a Caucasian population. Furthermore, the investigation of Ag(c,g) and of monoclonal BIP 45 antibody immunoaffinity for 30 individual plasma samples showed that BIP 45 bound strongly to Ag(c) factor, whereas it bound weakly to the allelic Ag(g) factor. This monoclonal antibody will be useful for the detection of the two corresponding apo B species designated apo B (Ag(c) factor, BIP+) and apo B (Ag(g) factor, BIP-).
Asunto(s)
Anticuerpos Monoclonales/inmunología , Apolipoproteínas B/inmunología , Especificidad de Anticuerpos , Apolipoproteínas B/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Epítopos , Humanos , Masculino , Linaje , Fenotipo , Polimorfismo GenéticoRESUMEN
Two population samples from South Africa, i.e. 555 Bantu-speaking Negroids and 75 Indians, were tested for selected immunogenetic specificities comprising the Ag polymorphism. Within the Negroid sample a new Ag phenotype (i.e. the 49th) was discovered. Interpopulational comparisons involving the present two, as well as three previously studied samples, reveal characteristic differences in regard to the frequency distribution of Ag phenotypes, to the Ag allele frequencies and to the occurrence of Ag haplotypes. These results are discussed. All the data could be interpreted satisfactorily in terms of the genetic model regarding the Ag system as postulated by Bütler and his co-workers.