Association of Functional Polymorphisms of the Human Tryptophan

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Transcript Association of Functional Polymorphisms of the Human Tryptophan

From: Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for
Bipolar Disorder in Han Chinese
Arch Gen Psychiatry. 2007;64(9):1015-1024. doi:10.1001/archpsyc.64.9.1015
Figure Legend:
Representation of the linkage disequilibrium structure in the tryptophan hydroxylase 2 gene (TPH2) in control subjects (A) and
patients with bipolar disorder (B). Pairwise linkage disequilibrium of the TPH2 single-nucleotide polymorphisms was plotted using
the graphical overview of linkage disequilibrium program (http://www.sph.umich.edu/csg/abecasis/GOLD/) with the absolute
standardized linkage disequilibrium coefficient (D′) obtained in patients with bipolar disorder and matched healthy control subjects.
Red indicates complete linkage (D′, ±1); blue, no
linkage©(D′,
0).American
The 6 loci
are numbered in order from the 5′ to 3′ orientation.
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2017
Medical
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From: Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for
Bipolar Disorder in Han Chinese
Arch Gen Psychiatry. 2007;64(9):1015-1024. doi:10.1001/archpsyc.64.9.1015
Figure Legend:
Effect of tryptophan hydroxylase 2 gene (TPH2) promoter polymorphism on gene expression in the reporter system. A, Promoter
activity of the TPH2 T − 703G and T − 473A polymorphisms. The human neuroblastoma cell lines SH-SY5Y and IMR-32 were
transfected with plasmid constructs containing different haplotype combinations for single-nucleotide polymorphisms (SNPs)
T − 703G and T − 473A. Luciferase activities were measured in luciferase units relative to the empty vector (pGL3-B). Data were
normalized to protein concentration (in micrograms)
and then
analyzed
using
the 2-sample ttest. All assays were performed in
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© 2017
American
Medical
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of download:
4/11/2017
triplicate,
and the levels
of promoter activity are expressed
as
mean
±
SD.
Although
luciferase activities were similar between
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haplotype TT, TA, and GT transfectants, significant differences were detected for the comparisons between haplotype GA
From: Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for
Bipolar Disorder in Han Chinese
Arch Gen Psychiatry. 2007;64(9):1015-1024. doi:10.1001/archpsyc.64.9.1015
Figure Legend:
Interaction between the tryptophan hydroxylase genes (TPH1 and TPH2) increased the risk of bipolar disorder (BPD). The odd
ratios between different comparisons were plotted using a 3-dimensional plot. The y-axis is the scale of odds ratios that indicates
gene effects. The x-axis separates all subjects into 2 groups: those with the TPH2-TAG haplotype and those with all other
haplotypes. The z-axis divides these subgroups according to their TPH1 T-346G polymorphism. The data demonstrated that TPH1
interacts with TPH2 to modify the risk of BPD. Copyright © 2017 American Medical
Date of download: 4/11/2017
Association. All rights reserved.
From: Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for
Bipolar Disorder in Han Chinese
Arch Gen Psychiatry. 2007;64(9):1015-1024. doi:10.1001/archpsyc.64.9.1015
Figure Legend:
Both of the tryptophan hydroxylase genes (TPH1 and TPH2) are expressed in various regions of the human brain. Eight
complementary DNA libraries made from various sections of the human brain—total brain, amygdala, cerebellum, cerebral cortex,
frontal lobes, hippocampus, medulla oblongata, and pons—were used to assess the relative expression level of TPH1 and TPH2.
The expression levels of TPH1 and TPH2 were measured using quantitative real-time polymerase chain reaction with the human
brain complementary DNA panel. The relative expression
calculated
Copyright ©levels
2017 were
American
Medicalby normalizing the value of TPH1 or TPH2
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messenger
RNA (mRNA)
to the value of 18S rRNA
(the
ΔCt).
The
ΔCt
in
each
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brain (the ΔΔCt). The expression levels are represented by 2(−ΔΔCt) in the dual y-axis, and the axes on the left and right indicate the
From: Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for
Bipolar Disorder in Han Chinese
Arch Gen Psychiatry. 2007;64(9):1015-1024. doi:10.1001/archpsyc.64.9.1015
Figure Legend:
The C2755A polymorphism of the tryptophan hydroxylase 2 gene (TPH2) is highly conserved across species and affects TPH2
protein function. A, Sequence alignment of the N-terminal region of the TPH2 protein across species. Sequences include human
(Homo sapiens; gi:31795563), chimpanzee (Pan troglodyte; gi:55638559), cow (Bos taurus; gi:76660723), rat (Rattus norvegi;
gi:27753970), mouse (Mus musculus; gi:27734182), chicken (Gallus gallus; gi:47604924), dog (Canis familiars; gi:73968761),
torafugu (Takifugu rubripes; gi:74095987), and zebra
fish ©
(Danio
rerio; gi:47550885).
Sequences were aligned using the MultAlin
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2017 American
Medical
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program
(available4/11/2017
at http://bioinfo.genopole-toulouse.prd.fr/multalin/multalin.html)
with
the hierarchical clustering method. Numbers
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indicate positions of amino acids. Red and blue indicate that conservation at a given position is higher than 80% or ranges from 50%