Worm Breeder's Gazette 14(1): 86 (October 1, 1995)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Identification of onchocerciasis-related genes in C. elegans: onchocerciasis, anyone?

Tom Barnes, Siegfried Hekimi

Dept Biology, McGill University H3A 1B1 PQ Canada

Upstream of the unc-24 gene on IV is what appears to be a gene which
could encode a protein with significant similarity to a protein from the
parasitic nematode Onchocerca volvulus, the causative agent of
onchocerciasis, or river-blindness.  In this parasitic disease,
blindness arises from damage to both the anterior and posterior segments
of the eye.  The etiology of the posterior segment disease has
autoimmune qualities.  That is, it appears as if the pathogen evades
host responses in general by mimicking host antigens; this
hyporesponsiveness can fail, and when it does a cross-reaction with a
host antigen of the posterior segment of the eye appears to occur.
There is an Onchocerca protein that is a strong candidate to contain an
epitope implicated in this pathophysiology.  Antibodies against this 22K
protein, Ov39, cross-react with a 44K antigen located in human and
bovine retinal pigment epithelial cells, and innoculation of Lewis rats
with bacterially-produced parasite antigen efficiently induces eye
damage, to cite just some of the data.

This is the protein to which the proposed gene upstream of unc-24 bears
similarity, and we suggest the name ora-1 for onchocerciasis-related
antigen.  32P mutagenesis (or more accurately phosphate-decay
mutagenesis) frequently produces small deletions, and indeed, the pdi
allele of unc-24, e927, is a small deletion.  We describe this here
because it deletes ora-1.  We have therefore renamed this allele qmDf1.
However, qmDf1 homozygotes in the dissecting scope appear just like
other unc-24 homozygotes.  We have also identified a second C. elegans
member of this family from Consortium sequence, found on cosmid F40E10,
and for which we propose the name ora-2.  Thus either ora-1 mutants have
a subtle phenotype, or there is some redundancy between ora-1 and ora-2.
Ov39 (no more similar to either ORA-1 or ORA-2) is expressed in the
hypodermis and the somatic gonad in adult Onchocerca, and also in muscle
cells in microfilariae (ie dauer equivalents).  We would be interested
in hearing from anybody who wants to pursue the further characterization
of ora-1.