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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: 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. Copyright 2007 Medical Date of download: 5/13/2017 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: 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 Copyright © 2007 American Medical Date of download: 5/13/2017 triplicate, and the levels of promoter activity are expressed as mean ± SD. Although luciferase activities were similar between Association. All rights reserved. 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: 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 Copyright 2007 American Medical Date of download: program (available5/13/2017 at http://bioinfo.genopole-toulouse.prd.fr/multalin/multalin.html) with the hierarchical clustering method. Numbers Association. All rights reserved. indicate positions of amino acids. Red and blue indicate that conservation at a given position is higher than 80% or ranges from 50% 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 2007 were American Medicalby normalizing the value of TPH1 or TPH2 Date of download: 5/13/2017 messenger RNA (mRNA) to the value of 18S rRNA (the ΔCt). The ΔCt in each Association. All rights reserved.panel was then standardized using the ΔCt in the 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: 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 © 2007 American Medical Date of download: 5/13/2017 Association. All rights reserved.