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determined in stools collected for a 96-hour period following treatment
with albendazole, and total weight of the worms was determined. 39
Our initial genetic results demonstrated significant heritabilities for
each of the measures of Ascaris burden in the Jirel population. Egg counts
were significantly heritable with approximately 30% of the variation in
egg counts being attributable to genetic factors. Worm counts showed
a significant heritability, with approximately 36% of the variation in total
worm count being attributable to genetic factors. And finally, total worm
weight was significantly heritable with about 34% of the variation in total
worm weight attributable to genetic factors.
The results of these initial quantitative genetic studies of Ascaris in the
Jirel population strongly support the hypothesis that the individual
predisposition to infection repeatedly observed in earlier studies by other
investigators 27 e 29,41,42 was in fact due to genetic effects.
These results also appear to be consistent across host species. A heri-
tability of Ascaris egg counts of approximately 30% has since been found
in the pig model. 43
GENOME SCANS FOR GENES INFLUENCING
ASCARIS
INFECTION
To date, only two genome-wide scans for genes influencing traits
associated with Ascaris infection have been published. Of all the tech-
niques used to assess genetic influences on Ascaris infection, genome-
wide approaches are the most powerful (strongest) genetic approaches
because they are unbiased. All possible genetic factors are considered
with no a priori hypotheses governing the range of genes considered.
Work in the Jirel population of eastern Nepal involved a genome scan
of a total of 1258 individuals belonging to a single extended pedigree. 44,45
Ascaris egg counts were determined for each individual and each person
also was characterized for approximately 370 STR markers evenly spaced
across the autosomes. The first report generated from this scan localized
two genes influencing risk for Ascaris infection in the original core of the
Jirel pedigree which included 444 individuals, 27.2% of whom were
infected. 44 Because of the complexity of the pedigree, over 6200 pairs of
relatives informative for genetic analysis were present in the sample.
Two loci were found to exert significant effects on Ascaris burden in the
branch of the Jirel pedigree examined. 44 The strongest linkage signal was
found on chromosome 13 near the q terminus (13q32
q34). An excellent
candidate gene was located in the region TNFSF13B. The gene is an
important regulator of B cell activation and Ig secretion. 46 e 48 The other
significant quantitative trait locus influencing Ascaris worm burden was
located on chromosome 1 (1p32).
e
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