Modou Séré

Bio: Modou Séré is an academic researcher from Institut de recherche pour le développement. The author has contributed to research in topics: Population & Genetic distance. The author has an hindex of 4, co-authored 6 publications receiving 63 citations.

Comparison of different genetic distances to test isolation by distance between populations.

Abstract: Studying isolation by distance can provide useful demographic information. To analyze isolation by distance from molecular data, one can use some kind of genetic distance or coalescent simulations. Molecular markers can often display technical caveats, such as PCR-based amplification failures (null alleles, allelic dropouts). These problems can alter population parameter inferences that can be extracted from molecular data. In this simulation study, we analyze the behavior of different genetic distances in Island (null hypothesis) and stepping stone models displaying varying neighborhood sizes. Impact of null alleles of increasing frequency is also studied. In stepping stone models without null alleles, the best statistic to detect isolation by distance in most situations is the chord distance DCSE. Nevertheless, for markers with genetic diversities HS<0.4-0.5, all statistics tend to display the same statistical power. Marginal sub-populations behave as smaller neighborhoods. Metapopulations composed of small sub-population numbers thus display smaller neighborhood sizes. When null alleles are introduced, the power of detection of isolation by distance is significantly reduced and DCSE remains the most powerful genetic distance. We also show that the proportion of null allelic states interact with the slope of the regression of FST/(1-FST) as a function of geographic distance. This can have important consequences on inferences that can be made from such data. Nevertheless, Chapuis and Estoup's FreeNA correction for null alleles provides very good results in most situations. We finally use our conclusions for reanalyzing and reinterpreting some published data sets.

Null allele, allelic dropouts or rare sex detection in clonal organisms: simulations and application to real data sets of pathogenic microbes.

Abstract: Pathogens and their vectors are organisms whose ecology is often only accessible through population genetics tools based on spatio-temporal variability of molecular markers. However, molecular tools may present technical difficulties due to the masking of some alleles (allelic dropouts and/or null alleles), which tends to bias the estimation of heterozygosity and thus the inferences concerning the breeding system of the organism under study. This is especially critical in clonal organisms in which deviation from panmixia, as measured by Wright’s FIS, can, in principle, be used to infer both the extent of clonality and structure in a given population. In particular, null alleles and allelic dropouts are locus specific and likely produce high variance of Wright’s FIS across loci, as rare sex is expected to do. In this paper we propose a tool enabling to discriminate between consequences of these technical problems and those of rare sex. We have performed various simulations of clonal and partially clonal populations. We introduce allelic dropouts and null alleles in clonal data sets and compare the results with those that exhibit increasing rates of sexual recombination. We use the narrow relationship that links Wright’s FIS to genetic diversity in purely clonal populations as assessment criterion, since this relationship disappears faster with sexual recombination than with amplification problems of certain alleles. We show that the relevance of our criterion for detecting poorly amplified alleles depends partly on the population structure, the level of homoplasy and/or mutation rate. However, the interpretation of data becomes difficult when the number of poorly amplified alleles is above 50%. The application of this method to reinterpret published data sets of pathogenic clonal microbes (yeast and trypanosomes) confirms its usefulness and allows refining previous estimates concerning important pathogenic agents. Our criterion of superimposing between the FIS expected under clonality and the observed FIS, is effective when amplification difficulties occur in low to moderate frequencies (20-30%).

Population Genetics and Reproductive Strategies of African Trypanosomes: Revisiting Available Published Data.

Abstract: Trypanosomatidae are a dangerous family of Euglenobionta parasites that threaten the health and economy of millions of people around the world. More precisely describing the population biology and reproductive mode of such pests is not only a matter of pure science, but can also be useful for understanding parasite adaptation, as well as how parasitism, specialization (parasite specificity), and complex life cycles evolve over time. Studying this parasite's reproductive strategies and population structure can also contribute key information to the understanding of the epidemiology of associated diseases; it can also provide clues for elaborating control programs and predicting the probability of success for control campaigns (such as vaccines and drug therapies), along with emergence or re-emergence risks. Population genetics tools, if appropriately used, can provide precise and useful information in these investigations. In this paper, we revisit recent data collected during population genetics surveys of different Trypanosoma species in sub-Saharan Africa. Reproductive modes and population structure depend not only on the taxon but also on the geographical location and data quality (absence or presence of DNA amplification failures). We conclude on issues regarding future directions of research, in particular vis-a-vis genotyping and sampling strategies, which are still relevant yet, too often, neglected issues.

Revisiting FIS, FST, Wahlund Effects, and Null Alleles.

Abstract: Null alleles and Wahlund effects are well known causes of heterozygote deficits in empirical population genetics studies as compared to Hardy-Weinberg genotypic expectations. Some authors have theoretically studied the relationship of Wright's FIS computed from subsamples displaying a Wahlund effect and FST before the Wahlund effect, as can occasionally be obtained from populations of long-lived organisms. In the 2 subsample case, a positive relationship between these 2 parameters across loci would represent a signature of Wahlund effects. Nevertheless, for most organisms, getting 2 independent subsamples of the same cohort and population, one with a Wahlund effect and the other without, is almost never achieved and most of the time, empirical population geneticists only collect a single sample, with or without a Wahlund effect, or with or without null alleles. Another issue is that null allele increase FIS and FST altogether and thus may also create such correlation. In this article, I show that, for organisms collected in a single sample, which corresponds to the most common situation, Wahlund effects and null alleles affect the values of both FIS and FST though in the opposite direction. I also show that Wahlund effect produces no or weak positive correlation between the 2 F-statistics, while null alleles generate a strong positive correlation between them. Variation of these F-statistics is small and even minimized for FST under Wahlund effects as compared to null alleles. I finally propose a determination key to interpret data with heterozygote deficits.

The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of Trypanosoma brucei gambiense

Abstract: Background Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Cote d’Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci. Methodology/Principal findings 552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus). Conclusion This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of “one health” approaches to reach HAT elimination and contribute to AAT control in the studied foci.

Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

Abstract: Aquaglyceroporin-2 is a known determinant of melarsoprol–pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2–AQP3 tandem locus was described from melarsoprol–pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2–aqp3 null T. b. brucei does not. This proves that AQP2–AQP3 chimerization is the cause of melarsoprol–pentamidine cross-resistance in the T. b. gambiense isolates.