High-Throughput Genotyping of Common Chromosomal Inversions in the Afrotropical Malaria Mosquito Anopheles Funestus

Polymorphic chromosomal inversions have been implicated in local adaptation. In anopheline mosquitoes, inversions also contribute to epidemiologically relevant phenotypes such as resting behavior. Progress in understanding these phenotypes and their mechanistic basis has been hindered because the only available method for inversion genotyping relies on traditional cytogenetic karyotyping, a rate-limiting and technically difficult approach that is possible only for the fraction of the adult female population at the correct gonotrophic stage. Here, we focus on an understudied malaria vector of major importance in sub-Saharan Africa, Anopheles funestus. We ascertain and validate tag single nucleotide polymorphisms (SNPs) using high throughput molecular assays that allow rapid inversion genotyping of the three most common An. funestus inversions at scale, overcoming the cytogenetic karyotyping barrier. These same inversions are the only available markers for distinguishing two An. funestus ecotypes that differ in indoor resting behavior, Folonzo and Kiribina. Our new inversion genotyping tools will facilitate studies of ecotypic differentiation in An. funestus and provide a means to improve our understanding of the roles of Folonzo and Kiribina in malaria transmission.

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Chromosome arm specific patterns of polymorphism associated with chromosomal inversions in the major African malaria vector, Anopheles funestus

10.1101/068205 ◽

2016 ◽

Author(s):

Colince Kamdem ◽

Caroline Fouet ◽

Bradley J. White

Keyword(s):

Chromosomal Rearrangements ◽

Anopheles Funestus ◽

Sequence Divergence ◽

Sub Saharan Africa ◽

Chromosomal Inversions ◽

Genomic Analyses ◽

Chromosome Arm ◽

Sub Saharan ◽

Moisture Conditions ◽

Two Populations

AbstractChromosomal inversions facilitate local adaptation of beneficial mutations and modulate genetic polymorphism, but the extent of their effects within the genome is still insufficiently understood. The genome of Anopheles funestus, a malaria mosquito endemic to sub-Saharan Africa, contains an impressive number of paracentric polymorphic inversions, which are unevenly distributed among chromosomes and provide an excellent framework for investigating the genomic impacts of chromosomal rearrangements. Here we present results of a fine-scale analysis of genetic variation within the genome of two weakly differentiated populations of Anopheles funestus inhabiting contrasting moisture conditions in Cameroon. Using population genomic analyses, we found that genetic divergence between the two populations is centered on regions of the genome corresponding to three inversions, which are characterized by high values of FST, absolute sequence divergence and fixed differences. Importantly, in contrast to the 2L chromosome arm, which is collinear, nucleotide diversity is significantly reduced along the entire length of three autosome arms bearing multiple overlapping chromosomal rearrangements. These findings support the idea that interactions between reduced recombination and natural selection within inversions contribute to sculpt nucleotide polymorphism across chromosomes in An. funestus.

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An increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania

Scientific Reports ◽

10.1038/s41598-021-92741-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nancy S. Matowo ◽

Jackline Martin ◽

Manisha A. Kulkarni ◽

Jacklin F. Mosha ◽

Eliud Lukole ◽

...

Keyword(s):

Malaria Transmission ◽

Anopheles Funestus ◽

Sub Saharan Africa ◽

North West ◽

Vector Population ◽

Lake Zone ◽

Sub Saharan ◽

Long Lasting Insecticidal Nets ◽

Study District

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

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Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia

Malaria Journal ◽

10.1186/s12936-020-03467-3 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Ommer Mohammed Dafalla ◽

Mohammed Alzahrani ◽

Ahmed Sahli ◽

Mohammed Abdulla Al Helal ◽

Mohammad Mohammad Alhazmi ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Saudi Arabia ◽

Parasite Clearance ◽

Sub Saharan Africa ◽

Local Alignment ◽

Nucleotide Polymorphisms ◽

Gene Encoding ◽

Synonymous Mutations ◽

Search Tool ◽

Sub Saharan

Abstract Background Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. Methods One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). Results This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). Conclusions Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

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Women in Gabon

10.1093/acrefore/9780190277734.013.540 ◽

2021 ◽

Author(s):

Claire H. Griffiths

Keyword(s):

Central Africa ◽

Early Period ◽

Sub Saharan Africa ◽

African Women ◽

Female Population ◽

History Of ◽

Sub Saharan ◽

Tropical Woods ◽

New Research ◽

Export Revenue

Gabon, a small oil-rich country straddling the equator on the west coast of Africa, is the wealthiest of France’s former colonies. An early period of colonization in the 19th century resulted in disease, famine, and economic failure. The creation of French Equatorial Africa in 1910 marked the beginning of the sustained lucrative exploitation of Gabon’s natural resources. Gabon began off-shore oil production while still a colony of France. Uranium was also discovered in the last decade of the French Equatorial African empire. Coupled with rich reserves in tropical woods, Gabon has achieved, since independence in 1960, a higher level of export revenue per capita of population than any other country in sub-Saharan Africa in the postcolonial era. However, significant inequality has characterized access to wealth through paid employment throughout the recorded history of monetized labor. While fortunes have been amassed by a minute proportion of the female population of Gabon associated with the ruling regime, and a professional female middle-class has emerged, inequalities of opportunity and reward continue to mark women’s experience of life in this little-known country of West Central Africa. The key challenge facing scholars researching the history of women in Gabon remains the relative lack of historical resources. While significant strides have been made over the past decade, research on women’s history in Francophone Africa published in English or French remains embryonic. French research on African women began to make a mark in the last decade of colonization, notably with the work of Denise Paulme, but then remained a neglected area for decades. The publication in 1994 of Les Africaines by French historian Catherine Coquery-Vidrovitch was hailed at the time as a pioneering work in French historiography. But even this new research contained no analysis of and only a passing reference to women in Gabon.

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Evaluating two adjustment methods to extrapolate HIV prevalence from pregnant women to the general female population in sub-Saharan Africa

AIDS ◽

10.1097/00002030-200302140-00014 ◽

2003 ◽

Vol 17 (3) ◽

pp. 399-405 ◽

Cited By ~ 14

Author(s):

Massimo Fabiani ◽

Knut Fylkesnes ◽

Barbara Nattabi ◽

Emingtone O Ayella ◽

Silvia Declich

Keyword(s):

Pregnant Women ◽

Hiv Prevalence ◽

Sub Saharan Africa ◽

Female Population ◽

Sub Saharan

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Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB

Pathogens ◽

10.3390/pathogens10111487 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1487

Author(s):

Michael L. McHenry ◽

Eddie M. Wampande ◽

Moses L. Joloba ◽

LaShaunda L. Malone ◽

Harriet Mayanja-Kizza ◽

...

Keyword(s):

Genetic Variation ◽

Clinical Presentation ◽

Sub Saharan Africa ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Human Genomes ◽

Genome Wide ◽

Sub Saharan ◽

Cellular Replication

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.

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A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread inAnopheles gambiae

10.1101/592279 ◽

2019 ◽

Cited By ~ 1

Author(s):

Eric R. Lucas ◽

Kirk A. Rockett ◽

Amy Lynd ◽

John Essandoh ◽

Nelson Grisales ◽

...

Keyword(s):

Insecticide Resistance ◽

High Throughput ◽

Democratic Republic Of Congo ◽

Novel Mutation ◽

Sub Saharan Africa ◽

Mutant Form ◽

Evolutionary Origins ◽

Wild Type Counterpart ◽

Control Programmes ◽

Sub Saharan

AbstractThe spread of resistance to insecticides in the mosquito vectors of diseases such as malaria and dengue poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring the resistance status of mosquito populations is therefore essential, but obtaining direct phenotypic measurements of resistance is laborious and error-prone. In contrast, high-throughput genotyping offers the prospect of quick and repeatable estimates of resistance, while also allowing the genotypic markers of resistance to be tracked and studied. We developed a panel of 28 known or putative markers of resistance in the major malaria vectorAnopheles gambiae, which we use to test the association of these markers with resistance and to study their geographic distribution. We screened resistance-phenotypedAn.gambiaefrom populations from a wide swathe of Sub-Saharan Africa (Burkina Faso, Ghana, Democratic Republic of Congo (DRC) and Kenya), and found evidence of resistance association for four mutations, including a novel mutation in the detoxification geneGste2(Gste2-119V). We also identified a gene duplication inGste2which combines a resistance-associated mutant form of the gene with its wild-type counterpart, potentially alleviating the costs of resistance. Finally, we describe the distribution of the multiple evolutionary origins ofkdrresistance, finding unprecedented levels of diversity in the DRC. This panel represents the first step towards developing a quantitative predictive genotypic model of insecticide resistance that can be used to screenAn.gambiaepopulations and predict resistance status.

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Selective Introgression of Paracentric Inversions Between Two Sibling Species of the Anopheles gambiae Complex

Genetics ◽

10.1093/genetics/146.1.239 ◽

1997 ◽

Vol 146 (1) ◽

pp. 239-244

Author(s):

A della Torre ◽

L Merzagora ◽

J R Powell ◽

M Coluzzi

Keyword(s):

Anopheles Gambiae ◽

Behavioral Flexibility ◽

Introgressive Hybridization ◽

Sub Saharan Africa ◽

X Chromosomes ◽

Gambiae Complex ◽

Chromosomal Inversions ◽

Anopheles Gambiae Complex ◽

Two Generations ◽

Sub Saharan

The Anopheles gambiae complex includes the major vectors of malaria in sub-Saharan Africa where >80% of all world-wide cases occur. These mosquitoes are characterized by chromosomal inversions associated to the speciation process and to intraspecific ecological and behavioral flexibility. It has been postulated that introgressive hybridization has selectively transferred inversions on the second chromosome between A. gambiae and A. arabiensis, the two most important vectors of malaria. Here we directly test this hypothesis with laboratory experiments in which hybrid populations were established and the fate of chromosomal inversions were followed. Consistent with the hypothesis, “foreign” X chromosomes were eliminated within two generations, while some “foreign” second chromosomes persisted for the duration of the experiments and, judging from the excess of heterozygotes, established stable heterotic polymorphisms. Only those second chromosome inversions found naturally in the species could be introgressed.

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Mitochondrial genomes of Anopheles arabiensis, An. gambiae and An. coluzzii show no clear species division

F1000Research ◽

10.12688/f1000research.13807.2 ◽

2019 ◽

Vol 7 ◽

pp. 347 ◽

Cited By ~ 2

Author(s):

Mark J. Hanemaaijer ◽

Parker D. Houston ◽

Travis C. Collier ◽

Laura C. Norris ◽

Abdrahamane Fofana ◽

...

Keyword(s):

Sub Saharan Africa ◽

Mitochondrial Genomes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Chromosomal Form ◽

Operational Taxonomic Units ◽

Mitogenome Sequence ◽

Mitochondrial Sequences ◽

Sub Saharan ◽

Species Specific

Here we report the complete mitochondrial sequences of 70 individual field collected mosquito specimens from throughout Sub-Saharan Africa. We generated this dataset to identify species specific markers for the following Anopheles species and chromosomal forms: An. arabiensis, An. coluzzii (The Forest and Mopti chromosomal forms) and An. gambiae (The Bamako and Savannah chromosomal forms). The raw Illumina sequencing reads were mapped to the NC_002084 reference mitogenome sequence. A total of 783 single nucleotide polymorphisms (SNPs) were detected on the mitochondrial genome, of which 460 are singletons (58.7%). None of these SNPs are suitable as molecular markers to distinguish among An. arabiensis, An. coluzzii and An. gambiae or any of the chromosomal forms. The lack of species or chromosomal form specific markers is also reflected in the constructed phylogenetic tree, which shows no clear division among the operational taxonomic units considered here.

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The role of a single non-coding nucleotide in the evolution of an epidemic African clade of Salmonella

10.1101/175265 ◽

2017 ◽

Author(s):

Disa L. Hammarlöf ◽

Carsten Kröger ◽

Siân V. Owen ◽

Rocío Canals ◽

Lizeth Lacharme Lora ◽

...

Keyword(s):

Gene Expression Signature ◽

Systemic Infection ◽

Bloodstream Infections ◽

Human Infection ◽

Sub Saharan Africa ◽

Infection Model ◽

Nucleotide Polymorphisms ◽

Bacterial Survival ◽

Serovar Typhimurium ◽

Sub Saharan

Introductory ParagraphSalmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely-related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). We hypothesised that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes.Here we identified 3,597 transcriptional start sites (TSS) of the ST313 strain D23580, and searched for a gene expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance and modulated virulence in the chicken infection model. The PgtE protease is known to mediate systemic infection in animal models. We propose that high levels of expression PgtE of by African S. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection.Our finding of a functional role for an extra-genic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on non-coding regions of the genome.

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