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2016 ; 202
(4
): 1563-74
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The Dissection of Expression Quantitative Trait Locus Hotspots
#MMPMID26837753
Tian J
; Keller MP
; Broman AT
; Kendziorski C
; Yandell BS
; Attie AD
; Broman KW
Genetics
2016[Apr]; 202
(4
): 1563-74
PMID26837753
show ga
Studies of the genetic loci that contribute to variation in gene expression
frequently identify loci with broad effects on gene expression: expression
quantitative trait locus hotspots. We describe a set of exploratory graphical
methods as well as a formal likelihood-based test for assessing whether a given
hotspot is due to one or multiple polymorphisms. We first look at the pattern of
effects of the locus on the expression traits that map to the locus: the
direction of the effects and the degree of dominance. A second technique is to
focus on the individuals that exhibit no recombination event in the region, apply
dimensionality reduction (e.g., with linear discriminant analysis), and compare
the phenotype distribution in the nonrecombinant individuals to that in the
recombinant individuals: if the recombinant individuals display a different
expression pattern than the nonrecombinant individuals, this indicates the
presence of multiple causal polymorphisms. In the formal likelihood-based test,
we compare a two-locus model, with each expression trait affected by one or the
other locus, to a single-locus model. We apply our methods to a large mouse
intercross with gene expression microarray data on six tissues.