Biology Reference
In-Depth Information
In order to better understand any potential underlying functional
correlation, we further explored the G17226A variant in another data set
that we had available to us. This data set includes genome-wide tran-
scriptional profiles for participants in the San Antonio Family Heart
Study.
54
In this data set, the G17226Avariant in intron 3 was significantly
associated with increased gene expression of TNFSF13B in peripheral
blood mononuclear cells (PBMCs) from Mexican Americans (p
0.014).
This finding suggests that the observed variant may be reflecting a func-
tional signal relating to gene regulation. However, because we have not
exhaustively sequenced this gene relative to potential regulatory sites, our
result could still be due to linkage disequilibrium with another untyped
variant.
While our results continue to be consistent for a potential role of
TNFSF13B, they are not comprehensive. Ideally, we should assess all
possible sequence variation within the chromosome 13 QTL region. For
example, the IRS2 gene and its surrounding area should also be deeply
sequenced. Additionally, in an ideal situation, all individuals should be
directly sequenced or at least exactly imputed by utilizing the high
density SNP framework and given that appropriately chosen pedigree
members (i.e. those that capture the most of the originating founder
genomes and who are appropriately positioned to maximally allow for
exact Mendelian imputation of their descendants) are sequenced.
Regardless, TNFSF13B continues to be our primary positional candidate
gene for this QTL.
ΒΌ
OTHER CA
NDIDATE GENE STUDIES OF A
SCARIASIS
As reviewed by Quinnell,
55
there have been few candidate gene studies
of risk for Ascaris infection. The candidate gene studies that have been
conducted generally base their gene selection on the hypothesized rela-
tionship between asthma and helminthic infection.
56,57
Numerous
observations from epidemiological studies have suggested that resistance
to Ascaris infection may be associated with risk for asthma. As reviewed
by Hopkin,
58
it has been proposed that over evolutionary time, parasitic
worm infections may have selected for genes in humans that confer
resistance to Ascaris and susceptibility to asthma. Studies have demon-
strated a relationship between current Ascaris infection and decreased risk
for asthma
59
(see Chapter 2).
Based upon our original nomination of the 13q33-34 Ascaris infec-
tion influencing QTL, Acevedo and colleagues
60
assessed potential
genetic effects at three positional candidate genes (LIG4, TNFSF13B,
and IRS2) related to the immune system on quantitative levels of
immunoglobulins specific to Ascaris. They found that a missense
