The African malaria mosquito Anopheles gambiae, because of its epidemiological importance, was the first disease vector sequenced. In order to perform full genome annotation for An. gambiae, all sequences that have a biological role in this malaria vector must be identified. However, large gaps, incorrect orientation of some scaffolds, and unmapped sequences still pose a serious problem for accurate annotation and functional characterization of the genome. Knowledge of the full complement of mosquito genes, regulatory elements, and repetitive elements is incomplete without information about what lies in those missing sequences. Moreover, the abundance of incorrectly assembled "hybrid" M and S sequences in the current PEST genome assembly leads to the confusion between paralogous genes and genes from different hyplotypes. The assembly of gene-poor, repeat-rich heterochromatic regions is especially fragmented, and no gene from the heterochromatic Y chromosome has been found. The presence of readable polytene chromosomes and the paramount impact of malaria on public health make An. gambiae the best choice as the first vector with a highly finished genome assembly. The major thrust of this R21 project is to develop a high-quality genome assembly and to explore the genetic content of heterochromatin and the Y chromosome of Anopheles gambiae S-form using high- throughput technologies. The availability of equipment for automated in situ hybridization, next-generation sequencing, laser microdissection, and confocal microscopic analysis, as well as the expertise of the PI and Co-PI in cytogenetics and genomics, will ensure successful achievement of the project's goals. Briefly, the project's specific aims are to 1. Close interscaffold gaps in the S-form assembly by high-throughput whole-genome resequencing and targeted sequencing of BAC/fosmid clones. 2. Physically map and orient sequencing scaffolds to the polytene chromosomes. 3. Microdissect, sequence, and characterize the An. gambiae heterochromatin and Y chromosome. This project will greatly improve the current fragmented genome assembly for the An. gambiae S-form. A new genome assembly will enable researchers to work on functional annotation of the most complete sequencing set and to perform more comprehensive comparative genomics studies with other vectors and model organisms. The availability of genes from the Y chromosome will allow researchers to develop sex- specific vector control interventions and conduct phylogenetic analysis of the An. gambiae complex without complications of introgression. The scientific community will be able to access the new assembly from VectorBase for further mining and functional characterization of the An. gambiae genome.

Public Health Relevance

Targeting genes responsible for vector competence is a novel approach for controlling infectious diseases. A full genome annotation for the major African malaria vector Anopheles gambiae will facilitate identification of the epidemiologically important targets. Toward this goal, the proposed project will develop a high-quality genome assembly for Anopheles gambiae using high-throughput technologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI094289-02
Application #
8227943
Study Section
Special Emphasis Panel (ZRG1-VB-C (02))
Program Officer
Costero, Adriana
Project Start
2011-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$192,936
Indirect Cost
$67,936
Name
Virginia Polytechnic Institute and State University
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061
Hall, Andrew Brantley; Papathanos, Philippos-Aris; Sharma, Atashi et al. (2016) Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes. Proc Natl Acad Sci U S A 113:E2114-23
Fontaine, Michael C; Pease, James B; Steele, Aaron et al. (2015) Mosquito genomics. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science 347:1258524
Sharma, Atashi; Anderson, Troy D; Sharakhov, Igor V (2015) Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes. J Vis Exp :52041
Sharakhov, Igor V; Sharakhova, Maria V (2015) Heterochromatin, histone modifications, and nuclear architecture in disease vectors. Curr Opin Insect Sci 10:110-117
George, Phillip; Jensen, Silke; Pogorelcnik, Romain et al. (2015) Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster. Epigenetics Chromatin 8:50
George, Phillip; Sharma, Atashi; Sharakhov, Igor V (2014) 2D and 3D chromosome painting in malaria mosquitoes. J Vis Exp :e51173
Kinney, Nicholas Allen; Sharakhov, Igor V; Onufriev, Alexey V (2014) Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. PLoS One 9:e91943
Jiang, Xiaofang; Peery, Ashley; Hall, A Brantley et al. (2014) Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi. Genome Biol 15:459
Hall, Andrew Brantley; Timoshevskiy, Vladimir A; Sharakhova, Maria V et al. (2014) Insights into the preservation of the homomorphic sex-determining chromosome of Aedes aegypti from the discovery of a male-biased gene tightly linked to the M-locus. Genome Biol Evol 6:179-91
Kamali, Maryam; Marek, Paul E; Peery, Ashley et al. (2014) Multigene phylogenetics reveals temporal diversification of major African malaria vectors. PLoS One 9:e93580

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