Segmental Duplication Implicated in the Genesis of Inversion 2Rj of Anopheles gambiae

The malaria vector Anopheles gambiae maintains high levels of inversion polymorphism that facilitate its exploitation of diverse ecological settings across tropical Africa. Molecular characterization of inversion breakpoints is a first step toward understanding the processes that generate and maintain inversions. Here we focused on inversion 2Rj because of its association with the assortatively mating Bamako chromosomal form of An. gambiae, whose distinctive breeding sites are rock pools beside the Niger River in Mali and Guinea. Sequence and computational analysis of 2Rj revealed the same 14.6 kb insertion between both breakpoints, which occurred near but not within predicted genes. Each insertion consists of 5.3 kb terminal inverted repeat arms separated by a 4 kb spacer. The insertions lack coding capacity, and are comprised of degraded remnants of repetitive sequences including class I and II transposable elements. Because of their large size and patchwork composition, and as no other instances of these insertions were identified in the An. gambiae genome, they do not appear to be transposable elements. The 14.6 kb modules inserted at both 2Rj breakpoint junctions represent low copy repeats (LCRs, also called segmental duplications) that are strongly implicated in the recent (∼0.4Ne generations) origin of 2Rj. The LCRs contribute to further genome instability, as demonstrated by an imprecise excision event at the proximal breakpoint of 2Rj in field isolates

Malaria in Africa: Vector Species' Niche Models and Relative Risk Maps

A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km). Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes). For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis) these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The “additive” model assumes no interaction; the “minimax” model assumes maximum relative risk due to any vector in a cell; and the “competitive exclusion” model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease

Identification of selective sweeps in closely related populations of the house mouse based on microsatellite scans

Genome scans of polymorphisms promise to provide insights into the patterns and frequencies of positive selection Under natural conditions. The use of microsatellites as markers has the potential to focus on very recent. events, since in contrast to SNPs, their high mutation rates Should remove signatures of older events. We assess this concept here in a large-scale study. We have analyzed two population pairs of the house mouse, one pair of the subspecies Mus musculus domesticus and the other of M m. musculus. A total of 915 microsatellite loci chosen to cover the whole genome were assessed in a prescreening procedure, followed by individual typing of candidate loci. Schlotterer's ratio statistics (1nRH) were applied to detect loci with significant deviations from patterns of neutral expectation. For eight loci from each Population pair we have determined the size of the potential sweep Window and applied a second statistical procedure (linked locus statistics). For the two population pairs, we find five and four significant sweep loci, respectively, with an average estimated window size of 120 kb. On the basis of the analysis of individual allele frequencies, it is possible to identify the most recent sweep, for which we estimate an onset of 400-600 years ago. Given the known population history for the French-German population pair, we infer that the average frequency of selective sweeps in these populations is higher than 1 in 100 generations across the whole genome. We discuss the implications for adaptation processes in natural populations

Mitochondrial and ribosomal internal transcribed spacer (ITS2) diversity of the African malaria vector Anopheles funestus

The pattern of sequence variation in the mitochondrial DNA cytochrome b gene (cyt-b) and ribosomal DNA internal transcribed spacer 2 (ITS2) was examined in #Anopheles funestus$from Senegal and Burkina Faso in West Africa and Kenya in East Africa. From both West African countries, samples included individuals hypothesized to represent reproductively isolated taxa based upon different karyotypes and behaviours. Analysis of the cyt-b data revealed high haplotypic diversity (86$ sequences were almost monomorphic, with only two rare polymorphisms detected. The results from both markers are congruent and do not support the hypothesis of reproductively isolated chromosomal taxa within #An. funestus$. Whether the lack of support by mitochondrial DNA (mtDNA) and ribosomal DNA (rDNA) sequences is a result of the recent origin of the presumptive taxa, or of the absence of barriers to gene flow, remains to be elucidated, using more rapidly evolving markers such as microsatellites. (Résumé d'auteur

RISK OF RED BLOOD CELL ALLOIMMUNISATION IN RWANDA : ASSESSMENT OF PRETRANSFUSION CROSSMATCH TECHNIQUES USED IN DISTRICT HOSPITALS

Background: Screening of alloantibodies in patients is not yet done in district hospitals of Rwanda. The practice is to transfuse ABO/D compatible blood following an immediate spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM).Objectives: To assess the risk of red blood cell (RBC) alloimmunisation associated with the use of IS-XM compared to the IAT-XM in patients receiving blood transfusions in district hospitals in Rwanda.Design: A cross-sectional comparative descriptive study.Setting: Four Rwandan district hospitals. Kirehe and Nyanza hospitals used IS-XM while Muhima and Ruhengeri hospitals used IAT-XM.Subjects: Blood samples were obtained from 187 patients (101 with IS-XM and 86 with IAT-XM) transfused in January, February, October, and November of 2012.Results: The median age of blood recipients was 31 years (7 - 80) and 36% of them were male. Sixteen specific antibodies were identified in 12 patients: anti-RH1/D (2),anti-RH2/C (2), anti-RH3/E (2),anti-RH4/c  (1),anti-RH5/e (2),anti-LE1/Lea (2),anti-JK1/Jka (1),anti-JK2/Jkb (1),anti-KEL1/K (1),anti-MNS1/M (1),and autoantibody (1).The global prevalence of red blood cell (RBC) alloimmunisation was 6.4 % (12/187). That  prevalence was significantly higher in the IS-XM group (10.4%) than in the IAT-XM group (2.3%) with an odds ratio of 4.8; [95% CI=1.2-19.8]; and a p-value of 0.031.Conclusion: The prevalence of red blood cell (RBC) alloimmunisation in 187 patients receiving blood transfusions was 6.4% and was higher in recipients from hospitals using IS-XM, with Rhesus (RH) system antibodies widely predominant (56.2%).We recommend that IAT-XM be used in all district hospitals in Rwanda to minimise this risk