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Biomedical subjects

David W Severson

Publications and source records attributed to David W Severson.

14 recordsLinked to original sources
PubMed2006

VectorBase: a home for invertebrate vectors of human pathogens.

VectorBase (http://www.vectorbase.org/) is a web-accessible data repository for information about invertebrate vectors of human pathogens. VectorBase annotates and maintains vector genomes providing an integrated resource for the research community. Currently, VectorBase contains genome information for two organisms: Anopheles gambiae, a vector for the Plasmodium protozoan agent causing malaria, and Aedes aegypti, a vector for the flaviviral agents causing Yellow fever and Dengue fever.

Aedes↗
PubMed2006

Identification of quantitative trait loci for larval morphological traits in interspecific hybrids of Ochlerotatus triseriatus and Ochlerotatus hendersoni (Diptera: Culicidae).

Ochlerotatus triseriatus is the natural vector of La Crosse virus, a common cause of pediatric encephalitis in the United States; the closely related Ochlerotatus hendersoni transmits this virus at low frequency. Adults of these mosquito species are difficult to distinguish morphologically; however, the larval stages show species-specific differences in several characters. We identified genomic regions contributing to the differences between the larvae of these species through interspecific hybridizations. Quantitative trait loci (QTL) were identified by standard interval mapping techniques and by univariate marker association analyses. We examined 159 F(2) progeny from an Oc. hendersoni female by Oc. triseriatus male interspecific cross for variation in the number of saddle and siphon hair branches, attachment of the acus, and morphology of the anal papillae. At least one putative QTL was identified for each of the phenotypes examined. QTL most commonly mapped to linkage group (LG) III, although QTL were identified on LGI and LGII for three phenotypes each. Several of these QTL, and particularly those on LGIII, also map to genome regions controlling adult female body size and ability to orally transmit La Crosse virus. Further studies are required to elucidate the relationships among these traits and the impact they may have had on the ecological specialization and speciation of these mosquitoes.

Alleles↗
PubMed2006

Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement.

Control of arthropod-borne diseases based on population replacement with genetically modified non-competent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F(15). A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of Ae. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.

Aedes↗
PubMed2006

Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad.

An endogenous meiotic drive system was previously reported to be segregating in the yellow fever mosquito Aedes aegypti L. (Diptera: Culicidae) population in Trinidad. The meiotic driver (M(D)) is tightly linked to the male determining locus and selectively targets sensitive responders linked to the female determining allele, causing fragmentation of female gametes. This results in highly male-biased progeny. The M(D) system was initially studied as a genetic tool for population control with limited success, but recently interest has focused on its potential for population replacement. This study examines the distribution and dynamics of the M(D) system in Trinidad natural populations. We obtained ovitrap samples from seven geographically distinct regions and determined the allele frequencies of the driver (M(D)) and sensitive (m(s)) versus insensitive (m(i)) responders, respectively. Frequencies of the M(D) allele ranged from 0.1 to 0.5 and were low at the two major port cities, Port of Spain and San Fernando, suggesting the effects of frequent immigration by non-driving genotypes. Frequencies of the m(i) allele ranged from 0.4 to 0.7, suggesting the effects of strong selection by the driver. In addition, our results show that the driver and sensitivity of responders in the Trinidad populations are highly polymorphic. Continued studies of the dynamics of the M(D) system in natural populations are critical to considerations of its use in population replacement.

Aedes↗
PubMed2005

Quantitative genetics of vector competence for La Crosse virus and body size in Ochlerotatus hendersoni and Ochlerotatus triseriatus interspecific hybrids.

La Crosse virus is a leading cause of pediatric encephalitis in the United States. The mosquito Ochlerotatus triseriatus is an efficient vector for La Crosse virus, whereas the closely related O. hendersoni transmits only at very low rates. Quantitative trait loci (QTL) affecting the ability to orally transmit this virus and adult body size were identified in 164 F(2) female individuals from interspecific crosses of O. hendersoni females and O. triseriatus males using a combination of composite interval mapping (CIM), interval mapping (IM) for binary traits, and single-marker mapping. For oral transmission (OT), no genome locations exceeded the 95% experimentwise threshold for declaring a QTL using IM, but single-marker analysis identified four independent regions significantly associated with OT that we considered as tentative QTL. With two QTL, an increase in OT was associated with alleles from the refractory vector, O. hendersoni, and likely reflect epistatic interactions between genes that were uncovered by our interspecific crosses. For body size, two QTL were identified using CIM and a third tentative QTL was identified using single-marker analysis. The genome regions associated with body size also contain three QTL controlling OT, suggesting that these regions contain either single genes with pleiotropic effects or multiple linked genes independently determining each trait.

Animals↗
PubMed2005

Michelob_x is the missing inhibitor of apoptosis protein antagonist in mosquito genomes.

Apoptosis is implicated in the life cycle of the malaria parasite in mosquitoes. The genome project for the primary malaria vector Anopheles gambiae showed a significant expansion of the inhibitor of apoptosis protein (IAP) and caspase gene families in comparison with Drosophila. However, because of extensive sequence divergence, no orthologue was identified for the reaper/grim-like IAP antagonist genes that have a pivotal role in cell death regulation in Drosophila. Using a customized searching strategy, we identified michelob_x(mx), a gene not predicted by the genome project, as the missing IAP antagonist in the An. gambiae and other mosquito genomes. Mx has a highly conserved amino-terminal IAP-binding motif. Expression of Mx induces rapid cell death in insect cell lines and is a potent tissue ablator in vivo. Its proapoptotic activity is totally dependent on the IAP-binding motif. Like reaper in Drosophila, mx is transcriptionally induced by ultraviolet irradiation to mediate cell death.

Aedes↗
PubMed2004

An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus.

A cDNA sequence encoding a Drosophila Ace-paralogous acetylcholinesterase (AChE) precursor of 701 amino acid residues was identified as the second AChE gene (Ace2) transcript from Culex tritaeniorhynchus. The Ace2 gene is tightly linked to organophosphorus insecticide (OP)-insensitivity of AChE on chromosome 2. The cDNA sequences were compared between an insecticide-susceptible strain and the resistant strain, TYM, that exhibits a 870-fold decrease in fenitroxon-sensitivity of AChE. Two amino acid substitutions were present in TYM mosquitoes. One is F455W whose homologous position in Torped AChE (Phe331) is located in the vicinity of the catalytic His in the acyl pocket of the active site gorge. The other substitution is located to a C-terminal Ile697 position that apparently seems to be excluded from the mature protein and is irrelevant to catalytic activity. The F455W replacement in the Ace2 gene is solely responsible for the insecticide-insensitivity of AChE in TYM mosquitoes.

Acetylcholinesterase↗
PubMed2004

Aedes aegypti genomics.

The mosquito, Aedes aegypti, is the primary, worldwide arthropod vector for the yellow fever and dengue viruses. As it is also one of the most tractable mosquito species for laboratory studies, it has been and remains one of the most intensively studied arthropod species. This has resulted in the development of detailed genetic and physical maps for Ae. aegypti and considerable insight into its genome organization. The research community is well-advanced in developing important molecular tools that will facilitate a whole genome sequencing effort. This includes generation of BAC clone end sequences, physical mapping of selected BAC clones and generation of EST sequences. Whole genome sequence information for Ae. aegypti will provide important insight into mosquito chromosome evolution and allow for the identification of genes and gene function. These functions may be common to all mosquitoes or perhaps unique to individual species, possibly specific to host-seeking and blood-feeding behaviors, as well as the innate immune response to pathogens encountered during blood-feeding. This information will be invaluable to the global effort to develop novel strategies for preventing arthropod-borne disease transmission.

Aedes↗
PubMed2004

Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera: Culicidae).

We have initiated efforts to determine the molecular basis for the M(D) meiotic drive system in the mosquito, Aedes aegypti. The effect of the M(D) gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M(D) system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M(D) gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible m(s) females result in progeny with highly biased sex ratios, wherein only approximately 14.7% females are produced. We discuss the potential for identifying M(D) candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M(D) and insensitive m3 alleles are likely segregating.

Aedes↗
PubMed2003

Dynamics of molecular markers linked to the resistance loci in a mosquito-Plasmodium system.

Models on the evolution of resistance to parasitism generally assume fitness tradeoffs between the costs of being parasitized and the costs associated with resistance. This study tested this assumption using the yellow fever mosquito Aedes aegypti and malaria parasite Plasmodium gallinaceum system. Experimental mosquito populations were created by mixing susceptible and resistant strains in equal proportions, and then the dynamics of markers linked to loci for Plasmodium resistance and other unlinked neutral markers were determined over 12 generations. We found that when the mixed population was maintained under parasite-free conditions, the frequencies of alleles specific to the susceptible strain at markers closely linked to the loci for resistance (QTL markers) as well as other unlinked markers increased significantly in the first generation and then fluctuated around equilibrium frequencies for all six markers. However, when the mixed population was exposed to an infected blood meal every generation, allele frequencies at the QTL markers for resistance were not significantly changed. Small population size caused significant random fluctuations of allele frequencies at all marker loci. Consistent allele frequency changes in the QTL markers and other unlinked markers suggest that the reduced fitness in the resistant population has a genome-wide effect on the genetic makeup of the mixed population. Continuous exposure to parasites promoted the maintenance of alleles from the resistant Moyo-R strain in the mixed population. The results are discussed in relation to the proposed malaria control strategy through genetic disruption of vector competence.

Aedes↗
PubMed2003

Utility of comparative anchor-tagged sequences as physical anchors for comparative genome analysis among the Culicidae.

The development of comparative genetic maps in multiple species of mosquitoes could prove extremely useful in the search for those genes that contribute to mosquito vector competence or genes associated with other phenotypes of interest. To effectively compare these gene maps, markers must be developed that are based on chromosomal regions conserved throughout the Culicidae. We designed 35 polymerase chain reaction (PCR) primer pairs based upon orthlogous exons in Aedes aegypti and Drosophila melanogaster or Anopheles gambiae. Twenty-three of the primers yielded a single PCR product in at least one dipteran, in addition to Ae. aegypti, when screened with genomic DNA from seven dipterans, including five mosquito species. Eight of the primers amplified a single PCR product in only Ae. aegypti, while four primer pairs gave no PCR product in any species. The 23 successful comparative anchor-tagged sequence primer pairs give broad genome coverage in Ae. aegypti, and more importantly demonstrate an efficient strategy for developing comparative anchor marker loci for any species of Culicidae.

Amino Acid Sequence↗