Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1

<p>Abstract</p> <p>Background</p> <p>Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin γ and κ-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against <it>Plasmodium vivax</it>.</p> <p>Methods</p> <p>Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to <it>P. vivax </it>apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses.</p> <p>Results</p> <p>IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (<it>P </it>= 0.004, <it>P </it>= 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype.</p> <p>Conclusions</p> <p>Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to <it>P. vivax </it>malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.</p

GM and KM immunoglobulin allotypes in the Galician population: new insights into the peopling of the Iberian Peninsula

<p>Abstract</p> <p>Background</p> <p>The current genetic structure of Iberian populations has presumably been affected by the complex orography of its territory, the different people and civilizations that settled there, its ancient and complex history, the diverse and persistent sociocultural patterns in its different regions, and also by the effects of the Iberian Peninsula representing a refugium area after the last glacial maximum. This paper presents the first data on <it>GM </it>and <it>KM </it>immunoglobulin allotypes in the Galician population and, thus, provides further insights into the extent of genetic diversity in populations settled in the geographic extremes of the Cantabrian region of northern Spain. Furthermore, the genetic relationships of Galicians with other European populations have been investigated.</p> <p>Results</p> <p>Galician population shows a genetic profile for <it>GM </it>haplotypes that is defined by the high presence of the European Mediterranean <it>GM</it>*<it>3 23 5* </it>haplotype, and the relatively high incidence of the African marker <it>GM*1,17 23' 5*</it>. Data based on comparisons between Galician and other Spanish populations (mainly from the north of the peninsula) reveal a poor correlation between geographic and genetic distances (<it>r </it>= 0.30, <it>P </it>= 0.105), a noticeable but variable genetic distances between Galician and Basque subpopulations, and a rather close genetic affinity between Galicia and Valencia, populations which are geographically separated by a long distance and have quite dissimilar cultures and histories. Interestingly, Galicia occupies a central position in the European genetic map, despite being geographically placed at one extreme of the European continent, while displaying a close genetic proximity to Portugal, a finding that is consistent with their shared histories over centuries.</p> <p>Conclusion</p> <p>These findings suggest that the population of Galicia is the result of a relatively balanced mixture of European populations or of the ancestral populations that gave rise to them. This would support the importance of the migratory movements that have taken place in Europe over the course of recent human history and their effects on the European genetic landscape.</p

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians