Late-acting dominant lethal genetic systems and mosquito control.

BACKGROUND: Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. RESULTS: We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. CONCLUSION: Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease control.

Whole genome analysis of a Vietnamese trio.

We here present the first whole genome analysis of an anonymous Kinh Vietnamese (KHV) trio whose genomes were deeply sequenced to 30-fold average coverage. The resulting short reads covered 99.91 percent of the human reference genome (GRCh37d5). We identified 4,719,412 SNPs and 827,385 short indels that satisfied the Mendelian inheritance law. Among them, 109,914 (2.3 percent) SNPs and 59,119 (7.1 percent) short indels were novel. We also detected 30,171 structural variants of which 27,604 (91.5 percent) were large indels. There were 6,681 large indels in the range 0.1-100 kbp occurring in the child genome that were also confirmed in either the father or mother genome. We compared these large indels against the DGV database and found that 1,499 (22.44 percent) were KHV specific. De novo assembly of high-quality unmapped reads yielded 789 contigs with the length greater than or equal to 300 bp. There were 235 contigs from the child genome of which 199 (84.7 percent) were significantly matched with at least one contig from the father or mother genome. Blasting these 199 contigs against other alternative human genomes revealed 4 novel contigs. The novel variants identified from our study demonstrated the necessity of conducting more genome-wide studies not only for Kinh but also for other ethnic groups in Vietnam.