DOCSLIB.ORG

Association of BET1L and TNRC6B with Uterine Leiomyoma Risk and Its

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Association of BET1L and TNRC6B with Uterine Leiomyoma Risk and Its www.nature.com/scientificreports OPEN Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Received: 30 January 2018 Accepted: 27 April 2018 Chinese population Published: xx xx xxxx Bailing Liu1,2, Tao Wang3, Jue Jiang1, Miao Li1, Wenqi Ma1, Haibin Wu3 & Qi Zhou1 Previous studies have shown that uterine leiomyomas (UL) are benign tumours with contributions from environmental and genetic factors. We aimed to replicate two initial signifcant genetic factors, TNRC6B and BET1L, in a Han Chinese population. A total of 2,055 study subjects were recruited, and 55 SNPs mapped to TNRC6B and BET1L were selected and genotyped in samples from these subjects. Genetic associations were analysed at both the single marker and haplotype levels. Associations between targeted SNPs and relevant clinical features of UL were analysed in case only samples. Functional consequences of signifcant SNPs were analysed by bioinformatics tools. Two SNPs, rs2280543 from BET1L (χ2 = 18.3, OR = 0.64, P = 1.87 × 10−5) and rs12484776 from TNRC6B (χ2 = 19.7, OR = 1.40, P = 8.91 × 10−6), were identifed as signifcantly associated with the disease status of UL. Rs2280543 was signifcantly associated with the number of fbroid nodes (P = 0.0007), while rs12484776 was signifcantly associated with node size (χ2 = 54.88, P = 3.44 × 10−11). Both SNPs were a signifcant eQTL for their genes. In this study, we have shown that both BET1L and TNRC6B contributed to the risk of UL in Chinese women. Signifcant SNPs from BET1L and TNRC6B were also identifed as signifcantly associated with the number of fbroid nodes and the size of the node, respectively. Uterine leiomyomas (UL), also known as uterine fbroids, are benign tumours in the uterus1. UL are typically identifed during the mid or late reproductive years in women, and they decrease in size afer menopause2. Te size and number of fbroids can vary among patients3. According to a systematic review published in 2017, the incidence of UL could be ranged from 217–3745 cases per 100,000 women-years4. In general, the prevalence of UL in women ranges from 20% in Europeans to as high as 80% in African-American women4,5. No symptoms can be identifed in more than 50% of women with UL6. For the remaining women with UL, their clinical symptoms can range from abnormal bleeding and pelvic pain to infertility and pregnancy complications6. Evidence from multiple studies has shown that UL have contributions from both environmental and genetic factors7–9. Early familial aggregation and twin studies have identifed a signifcant genetic component to UL pre- disposition10,11. Makinen et al. performed a whole-exome sequencing study on 18 UL patients and identifed the MED12 gene as contributing to tumourigenesis12. In a GWAS based on Japanese populations conducted in 2011, three loci on chromosomes 10q24.33, 22q13.1, and 11p15.5 were identifed to be signifcantly associ- ated with the disease status of UL13. Tese three loci included several genes such as STE20 Like Kinase (SLK), Oligosaccharide-Binding Fold-Containing Protein 1 (OBFC1), Trinucleotide Repeat Containing 6B (TNRC6B), Outer Dense Fiber 3 (ODF3), Bet1 Golgi Vesicular Membrane Trafcking Protein Like (BET1L), RIC8 Guanine Nucleotide Exchange Factor A (RIC8A), and Sirtuin 3 (SIRT3). Since then, several follow up studies have tried to replicate these initial GWAS fndings using study samples based on other ethnic groups14–16. However, the results of these subsequent studies have not been concordant and have, at times, been contradictory. More studies with large sample sizes are still needed to confrm these previous hits. In this study, we attempted to replicate two initial signifcant loci, TNRC6B and BET1L, identifed in a GWAS conducted by Cha et al.13 by using study subjects with Chinese Han ancestry. A total of 2,055 study subjects were 1Department of Ultrasound, the Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China. 2Department of Ultrasound, Children’s Hospital of Xi’an, Xi’an, Shaanxi, China. 3Department of Pediatrics, Children’s Hospital of Xi’an, Xi’an, Shaanxi, China. Correspondence and requests for materials should be addressed to Q.Z. (email: [email protected]) SCIENTIFIC REPORTS | (2018) 8:7401 | DOI:10.1038/s41598-018-25792-z 1 www.nature.com/scientificreports/ Subjects (N = 2,055) Characteristics UL patients (N = 674) Controls(N = 1,381) P-value Age, mean ± SD (years) 38.3 ± 7.22 38.2 ± 7.34 0.78 BMI, mean ± SD (kg/m2) 23.7 ± 1.37 23.6 ± 1.30 0.12 Married (%) 647 (96.0) 1328 (96.2) 0.94 Age of menarche, mean ± SD (years) 13.5 ± 1.47 13.4 ± 1.38 0.12 Duration of menses, mean ± SD (days) 6.5 ± 1.52 6.7 ± 1.69 0.005 Menstrual cycle, mean ± SD (days) 28.8 ± 1.39 28.6 ± 1.67 0.003 Bleeding (%) 396 (58.5) NA NA Pain (%) 225 (33.4) NA NA Fibroid node (%) NA NA Single 228(33.8) Multiple 446(66.2) Node size (%) NA NA Small 79(11.7) Medium 434(64.4) Large 161(23.9) Table 1. Te clinical and demographic characteristics of the uterine leiomyoma and control groups. UL: uterine leiomyoma; BMI: body mass index; SD: standard deviation; NA: not available. recruited, and 55 SNPs mapped to TNRC6B and BET1L were selected and genotyped in samples from these subjects. In addition to genetic associations between these SNPs and the disease status of UL, we also examined potential associations between targeted SNPs and clinical characteristics of UL. Bioinformatics tools were also utilized to evaluate the potential biological functions of the targeted SNPs. Methods Study subjects. In the present study, a total of 674 women with UL and 1,381 healthy women, controls without any systematic disease, were recruited from the Second Afliated Hospital of Xi’an Jiaotong University between April 2013 and May 2017. All patients were diagnosed with UL by ultrasonography and confrmed by at least two senior physicians, and all subjects were screened for no other female reproductive system tumours, systemic disease or history of malignancy. Self-administered questionnaires were used to collect demographic data, and the characteristics of our study subjects are shown in Table 1. All participants were unrelated Han Chinese individuals, and the UL and control groups were matched by age and body mass index (BMI). Signifcant diferences were identifed for duration of menses (P = 0.005) and menstrual cycle (P = 0.003) between UL cases and healthy controls. Te size of UL was categorized into three groups (small, medium, and large) based on the diameter of the UL (small ≤2 cm, 2 cm <medium <4 cm, large ≥4 cm). If subjects were diagnosed with multiple UL, the largest one determined the size group. Te study protocol was approved by the Ethics Committee of Xi’an Jiaotong University in accordance with the ethical guidelines of the Declaration of Helsinki of 1975 (revised in 2008). Written informed consent was obtained from participants. SNP selection and Genotyping. We searched for all SNPs with a minor allele frequency (MAF) ≥0.05 within the regions of the TNRC6B and BET1L genes in the 1000 Genomes Chinese Han Beijing population (CHB). Ten, MAF ≥0.05 with pair-wise tagging and r2 ≥0.8 were used as the cut-of criteria during tag SNP selection, which generated 27 and 28 tag SNPs within the TNRC6B and BET1L genes, respectively. General infor- mation about these 55 selected SNPs is summarized in Supplemental Table S1. Most of the selected SNPs were non-coding SNPs. Genomic DNA was extracted from peripheral blood leukocytes according to the manufac- turer’s protocol (Genomic DNA kit, Axygen Scientifc Inc., California, USA). Genotyping was performed for all SNPs using the Sequenom Mass ARRAY RS1000 system (Sequenom, San Diego, California, USA). Te results were processed using Typer Analyser sofware, and genotype data were generated from the samples17. Case and control status was blinded during all genotyping processes for quality control. Five percent of the samples were repeated at random, and the results were 100% concordant. Statistical and Bioinformatics Methods. Hardy-Weinberg equilibrium was tested for each SNP within the control samples. χ2 tests were performed for each SNP to evaluate the diferences in allelic and genotypic distributions between UL cases and controls. Linkage disequilibrium (LD) blocks were constructed for both genes, and haplotype-based analyses were conducted for each block. Plink was utilized for the analyses mentioned above18. In addition to genetic association analyses focusing on disease status, we also analysed the potential link between signifcant SNPs and four clinical features of UL, including bleeding, pain, number of fbroid nodes, and size of the node, in a subset of our samples that included UL cases only. χ2 tests were performed for these analyses. In general, Bonferroni correction was applied to address multiple comparisons. For single marker-based association analyses, the threshold P value was 0.05/55 ≈ 9 × 10−4. Genomic control was applied to correct for the potential efects of population stratifcation19,20. Te null distribution of genomic infation factor λ was con- structed by 10,000 bootstrapping. SCIENTIFIC REPORTS | (2018) 8:7401 | DOI:10.1038/s41598-018-25792-z 2 www.nature.com/scientificreports/ Allelic Test Genotypic Test rs2280543(%) T (N = 538) C (N = 3,572) OR χ2 P* TT (N = 37) CT (N = 464) CC (N = 1,554) χ2** P* Patients 133 (9.8) 1,215 (90.2) 3 (0.4) 127 (18.8) 544 (80.8) Controls 405 (14.6) 2,357 (85.4) 0.64 18.3 1.87 × 10−5 34 (2.5) 337 (24.4) 1,010 (73.1) — 1.85 × 10−5 rs12484776(%) G (N = 999) A (N = 3,111) GG (N = 125) GA (N = 749) AA (N = 1,181) Patients 385 (28.6) 963 (71.4) 61 (9.1) 263 (39.0) 350 (51.9) Controls 614 (22.2) 2,148 (77.8) 1.40 19.7 8.91 × 10−6 64 (4.6) 486 (35.2) 831 (60.2) 21.7 1.94 × 10−5 Table 2.
Load more

Recommended publications
  • Signature Redacted Signatureredacted
    The biochemical basis for the cooperative action of microRNAs S ISTITUTE By By MAssACHUSEOFTECHNOLOGY > Daniel Briskin OCT 0 12019 B.S., Molecular Genetics (2012) LIBRARIES 0 Ohio State University SUBMITTED TO THE DEPARTMENT OF BIOLOGY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY AT THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY -SEPTEMBER-2019- -fve e 7-1012 © 2019 Massachusetts Institute of Technology All rights reserved Signature redacted Signature of Author: DanielBriskin Department of Biology 17 September 2019 Signature redacted Certified By:__ David P. Bartel Professor of Biology Thesis Supervisor Accepted By: Signatureredacted -V Stephen Bell Uncas and Helen Whitaker Professor of Biology Investigator, Howard Hughes Medical Institute Co-Director, Biology Graduate Committee 1 2 The biochemical basis for the cooperative action of microRNAs by Daniel Briskin Submitted to the Department of Biology on 17 September 2019 In partial fulfillment of the requirements for the degree of doctor of philosophy Abstract In metazoans, microRNAs (miRNAs) act to repress mRNAs through a combination of translational repression and target degradation. miRNAs predominantly pair within the 3' untranslated region (3' UTR) of the mRNA. In cells, closely spaced miRNA target sites within an mRNA can act cooperatively, leading to more repression of the target mRNA than expected by independent action at each site. This dissertation details the use of purified miRNA-AGO2 complexes, synthetic target RNAs, and a purified domain of TNRC6B that is able to simultaneously bind multiple AGO proteins. We examined the target site occupancy and affinities for miRNA-AGO2 binding in the absence and presence of TNRC6B, for target RNAs with a single miRNA site as well as multiple miRNA sites spaced at varying distances.
    [Show full text]
  • A Set of Regulatory Genes Co-Expressed in Embryonic Human Brain Is Implicated in Disrupted Speech Development
    Molecular Psychiatry https://doi.org/10.1038/s41380-018-0020-x ARTICLE A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development 1 1 1 2 3 Else Eising ● Amaia Carrion-Castillo ● Arianna Vino ● Edythe A. Strand ● Kathy J. Jakielski ● 4,5 6 7 8 9 Thomas S. Scerri ● Michael S. Hildebrand ● Richard Webster ● Alan Ma ● Bernard Mazoyer ● 1,10 4,5 6,11 6,12 13 Clyde Francks ● Melanie Bahlo ● Ingrid E. Scheffer ● Angela T. Morgan ● Lawrence D. Shriberg ● Simon E. Fisher 1,10 Received: 22 September 2017 / Revised: 3 December 2017 / Accepted: 2 January 2018 © The Author(s) 2018. This article is published with open access Abstract Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, CHD3 SETD1A WDR5 fi 1234567890();,: we discovered de novo mutations, implicating genes, including , and . In other probands, we identi ed novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech.
    [Show full text]
  • Autism and Cancer Share Risk Genes, Pathways, and Drug Targets
    TIGS 1255 No. of Pages 8 Forum Table 1 summarizes the characteristics of unclear whether this is related to its signal- Autism and Cancer risk genes for ASD that are also risk genes ing function or a consequence of a second for cancers, extending the original finding independent PTEN activity, but this dual Share Risk Genes, that the PI3K-Akt-mTOR signaling axis function may provide the rationale for the (involving PTEN, FMR1, NF1, TSC1, and dominant role of PTEN in cancer and Pathways, and Drug TSC2) was associated with inherited risk autism. Other genes encoding common Targets for both cancer and ASD [6–9]. Recent tumor signaling pathways include MET8[1_TD$IF],[2_TD$IF] genome-wide exome-sequencing studies PTK7, and HRAS, while p53, AKT, mTOR, Jacqueline N. Crawley,1,2,* of de novo variants in ASD and cancer WNT, NOTCH, and MAPK are compo- Wolf-Dietrich Heyer,3,4 and have begun to uncover considerable addi- nents of signaling pathways regulating Janine M. LaSalle1,4,5 tional overlap. What is surprising about the the nuclear factors described above. genes in Table 1 is not necessarily the Autism is a neurodevelopmental number of risk genes found in both autism Autism is comorbid with several mono- and cancer, but the shared functions of genic neurodevelopmental disorders, disorder, diagnosed behaviorally genes in chromatin remodeling and including Fragile X (FMR1), Rett syndrome by social and communication genome maintenance, transcription fac- (MECP2), Phelan-McDermid (SHANK3), fi de cits, repetitive behaviors, tors, and signal transduction pathways 15q duplication syndrome (UBE3A), and restricted interests. Recent leading to nuclear changes [7,8].
    [Show full text]
  • HHS Public Access Author Manuscript
    HHS Public Access Author manuscript Author Manuscript Author ManuscriptOncogene Author Manuscript. Author manuscript; Author Manuscript available in PMC 2015 July 02. Published in final edited form as: Oncogene. 2015 January 2; 34(1): 94–103. doi:10.1038/onc.2013.523. Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma Paul N. Valdmanis1,2, Biswajoy Roy-Chaudhuri1,2, Hak Kyun Kim1,2, Leanne C. Sayles3, Yanyan Zheng3, Chen-Hua Chuang2,4,5, Deborah R. Caswell2,4,5, Kirk Chu1,2, Monte M. Winslow2,4,5, E. Alejandro Sweet-Cordero1,3,5, and Mark A. Kay1,2 1Department of Pediatrics, Stanford University, Stanford, CA, USA 2Department of Genetics, Stanford University, Stanford, CA, USA 3Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA 4Cancer Biology Program, Stanford University, Stanford, CA, USA 5Stanford Cancer Institute, Stanford University, Stanford, CA, USA Abstract Mice in which lung epithelial cells can be induced to express an oncogenic KrasG12D develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non- coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of KrasG12D tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing.
    [Show full text]
  • Molecular Architecture Underlying Fluid Absorption by the Developing Inner
    RESEARCH ARTICLE Molecular architecture underlying fluid absorption by the developing inner ear Keiji Honda1†, Sung Huhn Kim2‡, Michael C Kelly3, Joseph C Burns3§, Laura Constance2, Xiangming Li2#, Fei Zhou2, Michael Hoa4, Matthew W Kelley3, Philine Wangemann2*, Robert J Morell5, Andrew J Griffith1* 1Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States; 2Anatomy and Physiology Department, Kansas State University, Manhattan, United States; 3Developmental Neuroscience Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States; 4Auditory Development and Restoration Program, National Institute on *For correspondence: Deafness and Other Communication Disorders, National Institutes of Health, [email protected] (PW); Bethesda, United States; 5Genomics and Computational Biology Core, National [email protected] (AJG) Institute on Deafness and Other Communication Disorders, National Institutes of Present address: Health, Bethesda, United States †Otolaryngology Department, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan; ‡Department of Abstract Mutations of SLC26A4 are a common cause of hearing loss associated with Otorhinolaryngology, Head and enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse Neck Surgery, Yonsei University College of Medicine, Seoul, endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we Korea; §Decibel Therapeutics, show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid Cambridge, United States; absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and #Technique R and D-Drug S3226. Single-cell RNA-seq analysis of pre- and postnatal endolymphatic sacs demonstrates two Substance, GlaxoSmithKline types of differentiated cells.
    [Show full text]
  • Genomic Analysis of Follicular Dendritic Cell Sarcoma by Molecular
    Modern Pathology (2017) 30, 1321–1334 © 2017 USCAP, Inc All rights reserved 0893-3952/17 $32.00 1321 Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology Erica F Andersen1,2, Christian N Paxton2, Dennis P O’Malley3,4, Abner Louissaint Jr5, Jason L Hornick6, Gabriel K Griffin6, Yuri Fedoriw7, Young S Kim8, Lawrence M Weiss3, Sherrie L Perkins1,2 and Sarah T South1,2,9 1Department of Pathology, University of Utah, Salt Lake City, UT, USA; 2Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, UT, USA; 3Department of Pathology, Clarient/ Neogenomics, Aliso Viejo, CA, USA; 4Department of Pathology, M.D. Anderson Cancer Center/University of Texas, Houston, TX, USA; 5Department of Pathology, Massachusetts General Hospital, Boston, MA, USA; 6Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; 7Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA and 8Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes. Alterations of chromosomal regions 1p (55%), 2p (55%), 3p (82%), 3q (45%), 6q (55%), 7q (73%), 8p (45%), 9p (64%), 11q (64%), 13q (91%), 14q (82%), 15q (64%), 17p (55%), 18q (64%), and 22q (55%) were recurrent across the 11 samples showing abnormal genomic profiles.
    [Show full text]
  • Evaluating the Gene Targets of Micrornas Associated with Parkinson's Disease
    Evaluating the Gene Targets of microRNAs Associated with Parkinson’s Disease Kimberly Horn and Michael Sierk Bioinformatics Program, Saint Vincent College, Latrobe, PA Abstract Background: microRNA Gene Prediction Databases Results: Databases’ microRNA Predictions Results: Repeated Gene Target Predictions Cont. Almost 10 million people in the world's population are living with The top gene targets that were predicted for multiple Parkinson's disease and can only be officially diagnosed by miRNAs were selected in RStudio by grouping all the miRNAs’ symptoms. Parkinson's disease is a neurological disorder that https://academic.oup.com/nar/article/37/suppl_2/W266/1147920 prediction results by what gene target was predicted. This resulted does not display symptoms until significant nerve damage is in groups of predictions for each target, regardless of the miRNA. These groups were counted and the ten targets with the highest done. There is a need for biological testing to allow an earlier ElMMo is a Bayesian based gene prediction program that number of predictions were used to produce figure 4. Table 1 lists diagnosis. MicroRNAs are involved in messenger RNA translation focuses on genomics comparison to predict the gene targets. This each of the targets from figure 4 with the number of times they to protein as they control gene regulation. Abnormal levels of program focuses on the presence of potential gene targets in the were predicted and their gene function from UniProt. some microRNAs have been found in Parkinson's patients but the 3’ UTR site, compared to both the 3’ or 5’ sites. ElMMo is not In the miRNA target gene predictions, some genes were genes they regulate were unknown.
    [Show full text]
  • Transcriptional Regulators Are Upregulated in the Substantia Nigra
    Journal of Emerging Investigators Transcriptional Regulators are Upregulated in the Substantia Nigra of Parkinson’s Disease Patients Marianne Cowherd1 and Inhan Lee2 1Community High School, Ann Arbor, MI 2miRcore, Ann Arbor, MI Summary neurological conditions is an established practice (3). Parkinson’s disease (PD) affects approximately 10 Significant gene expression dysregulation in the SN and million people worldwide with tremors, bradykinesia, in the striatum has been described, particularly decreased apathy, memory loss, and language issues. Though such expression in PD synapses. Protein degradation has symptoms are due to the loss of the substantia nigra (SN) been found to be upregulated (4). Mutations in SNCA brain region, the ultimate causes and complete pathology are unknown. To understand the global gene expression (5), LRRK2 (6), and GBA (6) have also been identified changes in SN, microarray expression data from the SN as familial markers of PD. SNCA encodes alpha- tissue of 9 controls and 16 PD patients were compared, synuclein, a protein found in presynaptic terminals that and significantly upregulated and downregulated may regulate vesicle presence and dopamine release. genes were identified. Among the upregulated genes, Eighteen SNCA mutations have been associated with a network of 33 interacting genes centered around the PD and, although the exact pathogenic mechanism is cAMP-response element binding protein (CREBBP) was not confirmed, mutated alpha-synuclein is the major found. The downstream effects of increased CREBBP- component of protein aggregates, called Lewy bodies, related transcription and the resulting protein levels that are often found in PD brains and may contribute may result in PD symptoms, making CREBBP a potential therapeutic target due to its central role in the interactive to cell death.
    [Show full text]
  • 393LN V 393P 344SQ V 393P Probe Set Entrez Gene
    393LN v 393P 344SQ v 393P Entrez fold fold probe set Gene Gene Symbol Gene cluster Gene Title p-value change p-value change chemokine (C-C motif) ligand 21b /// chemokine (C-C motif) ligand 21a /// chemokine (C-C motif) ligand 21c 1419426_s_at 18829 /// Ccl21b /// Ccl2 1 - up 393 LN only (leucine) 0.0047 9.199837 0.45212 6.847887 nuclear factor of activated T-cells, cytoplasmic, calcineurin- 1447085_s_at 18018 Nfatc1 1 - up 393 LN only dependent 1 0.009048 12.065 0.13718 4.81 RIKEN cDNA 1453647_at 78668 9530059J11Rik1 - up 393 LN only 9530059J11 gene 0.002208 5.482897 0.27642 3.45171 transient receptor potential cation channel, subfamily 1457164_at 277328 Trpa1 1 - up 393 LN only A, member 1 0.000111 9.180344 0.01771 3.048114 regulating synaptic membrane 1422809_at 116838 Rims2 1 - up 393 LN only exocytosis 2 0.001891 8.560424 0.13159 2.980501 glial cell line derived neurotrophic factor family receptor alpha 1433716_x_at 14586 Gfra2 1 - up 393 LN only 2 0.006868 30.88736 0.01066 2.811211 1446936_at --- --- 1 - up 393 LN only --- 0.007695 6.373955 0.11733 2.480287 zinc finger protein 1438742_at 320683 Zfp629 1 - up 393 LN only 629 0.002644 5.231855 0.38124 2.377016 phospholipase A2, 1426019_at 18786 Plaa 1 - up 393 LN only activating protein 0.008657 6.2364 0.12336 2.262117 1445314_at 14009 Etv1 1 - up 393 LN only ets variant gene 1 0.007224 3.643646 0.36434 2.01989 ciliary rootlet coiled- 1427338_at 230872 Crocc 1 - up 393 LN only coil, rootletin 0.002482 7.783242 0.49977 1.794171 expressed sequence 1436585_at 99463 BB182297 1 - up 393
    [Show full text]
  • Exercise Alters Mouse Sperm Small Noncoding Rnas and Induces a Transgenerational Modification of Male Offspring Conditioned Fear and Anxiety
    OPEN Citation: Transl Psychiatry (2017) 7, e1114; doi:10.1038/tp.2017.82 www.nature.com/tp ORIGINAL ARTICLE Exercise alters mouse sperm small noncoding RNAs and induces a transgenerational modification of male offspring conditioned fear and anxiety AK Short1,2, S Yeshurun1, R Powell1, VM Perreau1,AFox1, JH Kim1, TY Pang1,3,4 and AJ Hannan1,3,4 There is growing evidence that the preconceptual lifestyle and other environmental exposures of a father can significantly alter the physiological and behavioral phenotypes of their children. We and others have shown that paternal preconception stress, regardless of whether the stress was experienced during early-life or adulthood, results in offspring with altered anxiety and depression-related behaviors, attributed to hypothalamic–pituitary–adrenal axis dysregulation. The transgenerational response to paternal preconceptual stress is believed to be mediated by sperm-borne small noncoding RNAs, specifically microRNAs. As physical activity confers physical and mental health benefits for the individual, we used a model of voluntary wheel-running and investigated the transgenerational response to paternal exercise. We found that male offspring of runners had suppressed reinstatement of juvenile fear memory, and reduced anxiety in the light–dark apparatus during adulthood. No changes in these affective behaviors were observed in female offspring. We were surprised to find that running had a limited impact on sperm-borne microRNAs. The levels of three unique microRNAs (miR-19b, miR-455 and miR-133a) were found to be altered in the sperm of runners. In addition, we discovered that the levels of two species of tRNA-derived RNAs (tDRs)—tRNA-Gly and tRNA-Pro—were also altered by running.
    [Show full text]
  • FOXP2 and Language Alterations in Psychiatric Pathology Salud Mental, Vol
    Salud mental ISSN: 0185-3325 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz Castro Martínez, Xochitl Helga; Moltó Ruiz, María Dolores; Morales Marin, Mirna Edith; Flores Lázaro, Julio César; González Fernández, Javier; Gutiérrez Najera, Nora Andrea; Alvarez Amado, Daniel Eduardo; Nicolini Sánchez, José Humberto FOXP2 and language alterations in psychiatric pathology Salud mental, vol. 42, no. 6, 2019, pp. 297-308 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz DOI: 10.17711/SM.0185-3325.2019.039 Available in: http://www.redalyc.org/articulo.oa?id=58262364007 How to cite Complete issue Scientific Information System Redalyc More information about this article Network of Scientific Journals from Latin America and the Caribbean, Spain and Journal's webpage in redalyc.org Portugal Project academic non-profit, developed under the open access initiative REVIEW ARTICLE Volume 42, Issue 6, November-December 2019 doi: 10.17711/SM.0185-3325.2019.039 FOXP2 and language alterations in psychiatric pathology Xochitl Helga Castro Martínez,1 María Dolores Moltó Ruiz,2,3 Mirna Edith Morales Marin,1 Julio César Flores Lázaro,4 Javier González Fernández,2 Nora Andrea Gutiérrez Najera,1 Daniel Eduardo Alvarez Amado,5 José Humberto Nicolini Sánchez1 1 Laboratorio de Genómica de Enfer- ABSTRACT medades Psiquiátricas y Neurode- generativas, Instituto Nacional de From the first reports of the linguist Noam Chomsky it has become clear that the development Medicina Genómica, Ciudad de Background. México, México. of language has an important genetic component. Several reports in families have shown the relationship 2 Departamento de Genética. Univer- between language disorders and genetic polymorphisms. The FOXP2 gene has been a fundamental piece sitat de València.
    [Show full text]
  • The Role of 4E-T in Translational Regulation and Mrna Decay
    The role of 4E-T in translational regulation and mRNA decay Dissertation der Mathematisch-Naturwissenschaftlichen Fakultät der Eberhard Karls Universität Tübingen zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) vorgelegt von Felix Alexander Paul Räsch aus Hermeskeil Tübingen 2020 Gedruckt mit Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Eberhard Karls Universität Tübingen. Tag der mündlichen Qualifikation: 05.08.2020 Dekan: Prof. Dr. Wolfgang Rosenstiel 1. Berichterstatter: Prof. Dr. Ralf-Peter Jansen 2. Berichterstatter: Prof. Dr. Patrick Müller This thesis describes work conducted in the laboratory of Prof. Dr. Elisa Izaurralde in the Department of Biochemistry at the Max Planck Institute for Developmental Biology, Tübingen, Germany, from February 2015 to May 2020. The work was supervised by Prof. Dr. Ralf-Peter Jansen at the Eberhard Karls University Tübingen, Germany, and was supported by a fellowship from the International PhD program of the MPI for Developmental Biology. I declare that this thesis is the product of my own work. The parts that have been published or where other sources have been used were cited accordingly. Work carried out by my colleagues was also indicated accordingly. Acknowledgements Acknowledgements This thesis would not have been possible without all the support I received during the last years for which I will be forever grateful. I would like to express my deepest gratitude to Prof. Dr. Elisa Izaurralde for giving me the opportunity to work in her lab and giving me support and guidance that shaped my understanding of science more than anything. She was a great mentor who cared deeply about the growth of her PhD students and her devotion to science was truly inspiring for me.
    [Show full text]