Biology Reference
In-Depth Information
in a mixed model along with the random effects of allele-sharing.
37
In
principle, the main effect may be tested in unrelated individuals as well,
although the test is then susceptible to confounding effects of population
stratification.
38
If one is so lucky as to have an actual functional variant in hand
or
e
a marker in perfect LD with a functional variant
measured genotype
(MG) analysis is necessarily the most powerful test of genetic effect.
However, LD falls off quite sharply with physical distance (by approxi-
mately 250 kb), which is both a blessing and a curse. It is why association
is capable of providing high-resolution positional data, but it also places
a severe limitation on detectable effect. The observed effect of a marker
locus
h
2
m
ΒΌ h
q
r
2
where
h
q
e
2
are the effect size of
the functional variant and the squared correlation between the marker
and functional genotypes, respectively. Thus, genome-wide studies of
association using 500,000 to 2M SNPs typically localize QTLs that have
effective regions of support of approximately 500 kb of sequence to search
through for functional variants. This is much smaller (
and
r
both unobserved
e
e
w
20
) than that
typically observed for a linkage-derived QTL.
QUANTITA
TIVE GENETICS STUDIES OF A
SCARIASIS
All genetic studies of Ascaris infection have employed the methods
(or closely related ones) briefly outlined above. The first quantitative
genetic study of susceptibility to Ascaris infection was conducted in the Jirel
population of eastern Nepal.
39
This study clearly demonstrated genetic
effects on risk for infection with A. lumbricoides using a variance compo-
nents approach for discriminating between genetic effects and household
effects on worm loads. Analyses of Ascaris burden were conducted using
data collected from 1261 members of a single complex pedigree which
provided outstanding statistical power. The single pedigree included over
26,000 pairs of relatives which were informative for the genetic analyses.
Additionally, because the entire population ultimately forms a single
pedigree, the problem of shared environment is greatly diminished since
the pedigree is composed of many (primarily) nuclear families living in
separate households. Thus, the confounding of shared exposure is mini-
mized when using very large pedigrees with individuals living in separate
households. The heritability of each measure of Ascaris worm burden
assessed in the pedigree members was determined using the variance
components approach as described above and implemented in SOLAR.
32,40
As mentioned previously, the heritability defines the proportion of the
variation in a trait which is attributable to additive genetic factors.
Ascaris burden was assessed in a variety of ways in this study. Egg
counts were determined from fecal samples, direct worm counts were
