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Comments on Johnson CD et al. (1995) International C. elegans Meeting "RESISTANCE TO IVERMECTIN IN C. ELEGANS AND OTHER FREE-LIVING NEMATODES" (0)
Overview
Johnson CD, & Clover R (1995). RESISTANCE TO IVERMECTIN IN C. ELEGANS AND OTHER FREE-LIVING NEMATODES presented in International C. elegans Meeting. Unpublished information; cite only with author permission.
We are using free-living nematodes to identify genes likely to be responsible for ivermectin resistance in parasitic nematodes. Previous studies revealed i) that low-level (5-15X) resistance in C. elegans is very common, conferred by recessive mutations in >30 genes, ii) that dominant resistance is less frequent, we find 6,000 recessives for each dominant mutation and iii) that high level resistance (>100X) is very rare, requiring recessive mutations in more than one gene. We observed a similar pattern of resistance in other free-living nematodes. Peter Hunt and Warwick Grant discovered that most low level resistance mutations also confer defects in dye-filling of the amphid neurons (Johnson, et al. WBG 13(3), 70). Many ivermectin resistance mutations are now known to be alleles of che, osm and dyf genes that control the dye-filling phenotype (Starich et al (1995) Genetics 139:171). Complementary results with other species show: i) that resistance in species that dye-fill is accompanied by dye-filling defects and iii) that species that do not dye-fill are "naturally" resistant to ivermectin. We are currently studying two new forms of resistance: 1) Dyf(+) low level resistance -- some mutations are unusual alleles of known genes -- and 2) mid-level (20-40X) resistance - - some mutations are in genes that contribute to high level resistance, other mutations are in new genes. Finally, we have been measuring the ivermectin resistance allele frequency in wild nematode populations. In one Dfy(+) diecious nematode species (not yet identified) we isolated 4 resistant strains (all Dyf) from the inbred progeny of 93 fertilized females -- apparent allele frequency in the wild: ~0.01 (4/93x4).