Genetic shifting: a novel approach for controlling vector-borne diseases

Abstract

Rendering populations of vectors of diseases incapable of transmitting pathogens through genetic methods has long been a goal of vector geneticists. We outline a method to achieve this goal that does not involve the introduction of any new genetic variants to the target population. Rather we propose that shifting the frequencies of naturally occurring alleles that confer refractoriness to transmission can reduce transmission below a sustainable level. The program employs methods successfully used in plant and animal breeding. Because no artificially constructed genetically modified organisms (GMOs) are introduced into the environment, the method is minimally controversial. We use Aedes aegypti and dengue virus (DENV) for illustrative purposes but point out that the proposed program is generally applicable to vector-borne disease control.

Keywords: genetic modification; genetically modified organisms (GMOs); vector control; vector-borne diseases.

Figure 1

Schematic of proposed selection schemes. Sample of ~200 females from the target populations are tested for competence. In Scheme I, mass selection, the 10% with lowest competence are chosen for the next generation. Two hundred offspring from these 10% are tested for competence, and the 10% least competent allowed to produce the population intended for release. Scheme II is family selection. The amount of competence testing is the same for each scheme. We illustrate only two generations of selection to avoid inbreeding and adaptation to laboratory conditions. If more than two generations of selection are needed, one should start with more than 200 from the field to avoid inbreeding. Alternatively, replicate parallel selected lines beginning with different field samples can be mixed to reduce inbreeding. Numbers suggested are simply examples, and the schemes can be modified to accommodate particulars of a given combination of vector and pathogen.

Figure 2

Hypothetical target population. One release may not move the mean (dotted lines) sufficiently to the left to affect or eliminate transmission. Subsequent releases would move the mean further. A threshold, though not known initially, would be crossed at some point with subsequent interruption of transmission.

Figure 3

Hypothetical case where phenotype is not a normal distribution. In this example, possibly mimicking DENV [9], a portion of females from the field target population show no DENV in the head after extrinsic incubation, while the rest form a continuum. Selection can be applied to the phenotypically non-competent fraction. Releases can be continued until the target population falls below the threshold for continued transmission.