Biology Reference
In-Depth Information
From an epidemiological viewpoint, changes in the temporal and
spatial distribution of
Ascaris
spp. and/or their hosts might also be
monitored using population genetic or metagenomic approaches.
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Another question of potential significance is whether
Ascaris
species are
developing genetic resistance against current anthelmintics, which
have been routinely used for many years. Although resistance against
such compounds had not been reported in the past for ascaridoids,
there is now evidence of emerging anthelmintic resistance in
Parascaris
equorum
populations in various countries.
93,94
With a reference genome
available for
A. suum
, it would now be possible to genetically compare
multiple populations of adult worms predicted to be resistant or
susceptible to one or more compounds, and then to assess links
between genotype and a drug-resistant phenotype on a genome-wide
scale. Transcriptomic analyses might also be used to underpin
comparisons between susceptible and resistant worms. Such analyses
might allow the definition of “resistance markers,” which could then be
used in a molecular test for the direct and specific molecular detection
of drug resistance. These examples suggest that there are numerous
exciting fundamental areas and questions to tackle using modern
genomic tools.
Comparative genome-wide sequencing of well-defined
A. suum
and
A. lumbricoides
samples could finally address the key question as
to the specific status of these two parasites.
9
In addition, the defi-
nition of a wide range of genetic markers for use in specific and
sensitive diagnostic tools could provide a foundation to address
questions regarding the complex network of ecological and biological
factors involved in parasite
environment interactions and the
immunological idiosyncrasies of porcine and human hosts in
endemic and non-endemic regions. It would also be particularly
interesting to explore the resistance and susceptibility of genotypes of
human and porcine hosts to
Ascaris
infection. For instance, eluci-
dating the relationship between host genotype and phenotype in
response to
Ascaris
and/or intervention strategy (e.g. treatment)
would be informative and could provide an understanding of the
genetic basis of disease.
The deep sequencing and bioinformatic approaches now established
provide the throughput and depth-of-coverage required to rapidly
define
de novo
the nuclear genomes of
A. lumbricoides
and other ascarioids
of human and animal health importance. Repertoires of drug targets can
now be inferred on a genome-wide scale. Such genomic-guided drug
target or drug discovery could have significant advantages over tradi-
tional screening methods. In
Ascaris
, at least 629 proteins with essential
homologues (associated with lethal phenotypes following gene pertur-
bation) in
C. elegans
and
D. melanogaster
were identified. Among these are
e
host
e