Bioinformatics Faculty Appointment Form - University of Memphis

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Oct 1, 2013 (4 years and 3 months ago)

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Title:

Bridging Genotype and Phenotype: Causal

Pathways from DNA to Complex Traits

Dr.
Yan Cui

University of Tennessee Health Science Center

Date:

Monday
,

October 22, 2007

Time:

4
:00
P
M
,

Place:

Link Auditorium, UT



Abstract:


Individual differences

in disease susceptibility and response to drugs are

complex traits with
significant genetic components. Many disease
-
related genetic loci have been mapped using linkage
analysis. However, the

genotype
-
phenotype connections do not expose the underlying cau
sal
pathways

through which gene variants operate on phenotypes. Gene transcription is an important
step in the process of phenotype manifestation. DNA polymorphisms

may cause variations in gene
expression and ultimately differences at

physiological and beh
avioral levels.

We integrated genotype
and gene expression data of genetic reference populations to systematically identify

the genetic loci
regulating gene expression. The gene expression levels were

treated as quantitative traits. QTL
mapping was used t
o identify chromosomal intervals that harbor sequence variants (polymorphisms)
causing variations

in gene expression. Classical higher
-
order phenotype data (e.g.

physiological and
behavioral phenotypes) was integrated with the newly

available large
-
scale g
ene expression trait data
of the same population. We

used Bayesian network to model the causal pathways through which
genetic

variants influence phenotypes. Structures and parameters of the Bayesian network models
were learned from the genotype, phenotype
and gene expression

data of the experimental
populations of mouse and yeast. These models were

used to predict the effects of genetic variants.
The prediction accuracy was assessed by cross
-
validation.