DOCSLIB.ORG

Download PDF Datastream

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Download PDF Datastream BROWN UNIVERSITY Dietary Lipids, Relevant Gene Networks, and Biological Interactions Underlying Obesity and Cardiovascular Disease A dissertation submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in Epidemiology at Brown University Providence, Rhode Island by Qing Liu May 2019 Ó Copyright 2019 by Qing Liu This dissertation by Qing Liu is accepted in its present form by the Department of Epidemiology as satisfying the dissertation requirement for the degree of Doctor of Philosophy. Date_______________ ___________________________________ Simin Liu, Advisor Recommended to the Graduate Council Date_______________ ___________________________________ Stephen T. McGarvey, Reader Date_______________ ___________________________________ Wen-Chih Wu, Reader Date_______________ ___________________________________ Xi Luo, Reader Approved by the Graduate Council Date_______________ ___________________________________ Andrew G. Campbell, Dean of the Graduate School iii iv Curriculum Vitae QING LIU School of Public Health Brown University 121 South Main Street Providence, RI 02903 Qing Liu graduated with a B.S./M.D. degree in preventive medicine from Peking University, Beijing, China. She then obtained a Sc.M. degree in Epidemiology from Brown University School of Public Health, and later joined the Ph.D. program in Epidemiology in Fall 2015, with Dr. Simin Liu as her primary advisor. At Brown University, Qing has been interested in genetic and nutritional epidemiology in the field of cardio-metabolic health outcomes. She had presented some of her thesis work at the American Heart Association’s annual conferences, and her research has contributed to publications in dietary lipids in relation to cardiovascular disease risk. During her Ph.D. program, she was a graduate teaching assistant for three courses in public health and interned at a healthcare consulting company. EDUCATION 2015 - present Brown University, School of Public Health (GPA: 4.0) Ph.D. candidate in Epidemiology Major Field of Study: nutritional epidemiology, molecular and genetic epidemiology, cardio-metabolic health outcomes 2013 - 2015 Brown University, School of Public Health (GPA: 4.0) M.S. in Epidemiology Thesis: Change in risks of cardiovascular disease in postmenopausal women associated with substituting different v types of margarine for butter. (Women’s Health Initiative Study) 2008 - 2013 Peking University, Health Science Center (GPA: 3.86) B.S./M.D. Concentration: Preventive Medicine AWARDS 2016 Runner-up of Doctoral Student or Post-doctoral Trainee Posters, Public Health Research Day 2015 2nd Place for Epi Department Conference Abstract Competition RESEARCH EXPERIENCE 01/2018 - present Providence VA Medical Center Research Assistant Develop research proposals and manuscripts for genetics and heart failure using data from the Women’s Health Initiative study, the Jackson Heart Study, and the Framingham Heart Study. 09/2013 - present Center for Global Cardiometabolic Health, Brown University Research Assistant Develop research proposals and manuscripts for nutrition, genetics, and cardio-metabolic health outcomes using data from the Women’s Health Initiative study, the Jackson Heart Study, and the Framingham Heart Study. vi Assisted on grant writing for dietary intervention trials among pregnant women and their offspring. 06/2017 - 08/2017 Center for Gerontology and Healthcare Research, Brown University Research Assistant Assisted on data analysis for a R01 project: Anticholinergic/sedentary medication and fracture among Nursing Home Residents 02/2014 - 08/2015 Center for Primary Care and Prevention, Brown University Research Assistant Developed research proposals and manuscripts for dietary/endogenous lipids and cardiovascular disease using data from the Women’s Health Initiative study. 05/2014 - 08/2014 The China Health and Retirement Longitudinal Study (CHARLS) Research Assistant Assisted data analysis and manuscript writing related to chronic kidney disease using data from the China Health and Retirement Longitudinal Study TEACHING EXPERIENCE 09/2016 - 12/2016 Brown University Teaching Assistant PHP 1700 Current Topics in Environmental Health Facilitated student discussions; wrote and graded exams. 09/2017 – 12/2017 Brown University Teaching Assistant and Guest Lecturer vii PHP 0320 Introduction to Public Health Facilitated student discussions; graded homework; guest lectured “Epidemiology: Study Design and Measures”. 09/2018 – 12/2018 Brown University Teaching Assistant PHP 2018 Epidemiology of Cardio-Metabolic Health Wrote and graded exams; prepared lab materials. PROFESIONAL WORK 06/2018 - 08/2018 Analysis Group, Inc. Summer Associate Led one project showing seasonal trend and regional distribution of clinical asthma exacerbation using insurance claim data. Developed study concepts, protocols, and assisted data analysis for multiple projects involving cancer therapies. PUBLICATIONS Liu Q, Lichtenstein AH, Matthan NR, et al. Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women. Lipids, 2017; 52(8):687-702. doi: 10.1007/s11745-017-4276-8. PMID: 28689316 Liu Q, Rossouw JE, Roberts MB, et al. Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease. Epidemiology, 2017; 28: 145–156. doi: 10.1097/EDE.0000000000000557. PMID: 27648593 Liu S, Liu Q. Personalized magnesium intervention to improve vitamin D metabolism: applying a systems approach for precision nutrition in large randomized trials of diverse populations. The American journal of clinical nutrition, 2018; 108 (6): 1159-1161. doi: https://doi.org/10.1093/ajcn/nqy294. viii Jankowich M, Elston B, Liu Q, et al. Restrictive Spirometry Pattern, Cardiac Structure and Function, and Incident Heart Failure in African Americans. The Jackson Heart Study. Ann Am Thorac Soc. 2018;15(10):1186-1196. doi: 10.1513/AnnalsATS.201803-184OC. PMID: 30011374 Zhang T, Zullo AR, Shireman TI, Lee Y, Mor V, Liu Q, et al. Epidemiology of hip fracture in nursing home residents with multiple sclerosis. Disabil Health J. 2018;11(4):591-597. doi: 10.1016/j.dhjo.2018.03.002. PMID: 29598927 Wang S, Chen R, Liu Q, et.al. Prevalence, awareness and treatment of chronic kidney disease among mid-aged and elderly: data from the China Health and Retirement Longitudinal Study. Nephrology, 2015 Jul; 20(7):474-84. doi: 10.1111/nep.12449. PMID: 25773384 Shengfeng Wang, Qing Liu, Qingmin Liu, et al. Assessment on the impact of smoking cessation counseling service and related influencing factors under comprehensive community-based intervention programs about the community medical staff in Hangzhou city. Chinese Journal of Epidemiology, 2014; 35(9):1002-6. PMID: 25492140 WORK UNDER REVIEW / IN PREPARATION “Discovery of Biological Pathways and Gene Networks for Heart Failure with Preserved and Reduced Ejection Fraction in Women Across Ethnicities” “Pathways and Gene Networks for Obesity and Potential Interactions with Dietary Lipid in Women Across Ethnicities” “Plasma Phospholipid Fatty Acid and Coronary Heart Disease Risk: A Nested Case-Control Study within the Women’s Health Initiative Observational Study.” “Magnesium Intake, Cognitive Impairment, and Dementia in Postmenopausal Women: Results from Women’s Health Initiative Memory Study” ix “Prospective associations of waist-to-height ratio with cardiovascular events of diabetic and non-diabetic postmenopausal women: Results from Women’s Health Initiative” “Prospective Associations of Added Sugar Intake with risk of Atherosclerotic Cardiovascular Disease: Results from Women’s Health Initiative” “A meta-analysis on subjective sleep quality and metabolic syndrome Running title: Sleep quality and metabolic syndrome” “Gene polymorphism, vitamin B and the risk of stroke or coronary heart disease: Results from the Women’s Health Initiative” ABSTRACTS AND PRESENTATIONS Liu Q, Chan KH, Luo X, Reiner AP, McGarvey ST, Liu S. Abstract 15406: Gene-Dietary Fat Interactions on Obesity Among Postmenopausal Women Participated in the Women's Health Initiative Study. Circulation. 136 (Suppl 1), A15406-A15406. Accepted for the American Heart Association 2017 Scientific Session. November 11-15th, 2017, Anaheim, CA, USA. Liu Q, Lichtenstein AH, Matthan NR, Liu S, Allison MA, Howard BV, Martin LW, Valdiviezo C, Manson JE, Eaton CB. Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women. Circulation. 133 (Suppl 1), AMP38-AMP38. Accepted for the American Heart Association EPI/Lifestyle 2016 Scientific Session. March 1- 4th, 2016, Phoenix, AZ, USA. Liu Q, Lichtenstein AH, Tinker LF, Neuhouser ML, Van Horn LV, Howard BV, Manson JE, Rossouw JE, Matthan NR, Allison MA, Martin LW, Li W, Snetselaar LG, Wang L, Eaton CB. Abstract MP39: Plasma Phospholipid Fatty Acid and Coronary Heart Disease Risk. Circulation. 133 (Suppl 1), x AMP39-AMP39. Accepted for the American Heart Association EPI/Lifestyle 2016 Scientific Session. March 1-4th, 2016, Phoenix, AZ, USA. JOURNAL REVIEW Reviewer – Medicine Reviewer – American Journal of Clinical Nutrition LANGUAGES English – Full professional proficiency Chinese - Native language SERVICES AND MEMBERSHIPS Member – The American Heart Association xi Preface This dissertation includes three publishable manuscripts (Chapter 2-4) reformatted to comply with the requirements of the Graduate School at Brown University. Chapter 1 is an overview of background, significance, and rationale in support of the specific aims of the research reported
Load more

Recommended publications
  • GWAS of Allometric Body-Shape Indices in UK Biobank Identifies Loci
    www.nature.com/scientificreports OPEN GWAS of allometric body‑shape indices in UK Biobank identifes loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer Sofa Christakoudi1,2*, Evangelos Evangelou1,3, Elio Riboli1 & Konstantinos K. Tsilidis1,3 Genetic studies have examined body‑shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the frst genome‑wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist‑to‑Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed‑models (BOLT‑LMM). One to two thirds of the loci identifed for allometric body‑shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region‑specifc associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants,
    [Show full text]
  • Exome Sequencing Identifies ZNF644 Mutations in High Myopia
    Exome Sequencing Identifies ZNF644 Mutations in High Myopia Yi Shi1,2., Yingrui Li3., Dingding Zhang1,2, Hao Zhang3, Yuanfeng Li1, Fang Lu1,2, Xiaoqi Liu1,2, Fei He1,2, Bo Gong1,2, Li Cai1, Ruiqiang Li3, Shihuang Liao4, Shi Ma1,2, He Lin1,2, Jing Cheng1,2, Hancheng Zheng3, Ying Shan3, Bin Chen4, Jianbin Hu4, Xin Jin5, Peiquan Zhao6, Yiye Chen6, Yong Zhang3, Ying Lin1,2,XiLi1, Yingchuan Fan4, Huanming Yang3, Jun Wang3, Zhenglin Yang1,2* 1 The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China, 2 Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China, 3 Beijing Genome Institute at Shenzhen, Shenzhen, China, 4 Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China, 5 Innovative Program for Undergraduate Students, School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China, 6 The Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China Abstract Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form.
    [Show full text]
  • Direct and Indirect Genetic Effects on Triglycerides Through Omics and Correlated Phenotypes Anne E
    Justice et al. BMC Proceedings 2018, 12(Suppl 9):22 https://doi.org/10.1186/s12919-018-0118-9 BMC Proceedings PROCEEDINGS Open Access Direct and indirect genetic effects on triglycerides through omics and correlated phenotypes Anne E. Justice1,2*, Annie Green Howard3,4, Lindsay Fernández-Rhodes1,4, Misa Graff1, Ran Tao5 and Kari E. North1 From Genetic Analysis Workshop 20 San Diego, CA, USA. 4 - 8 March 2017 Abstract Even though there has been great success in identifying lipid-associated single-nucleotide polymorphisms (SNPs), the mechanisms through which the SNPs act on each trait are poorly understood. The emergence of large, complex biological data sets in well-characterized cohort studies offers an opportunity to investigate the genetic effects on trait variability as a way of informing the causal genes and biochemical pathways that are involved in lipoprotein metabolism. However, methods for simultaneously analyzing multiple omics, environmental exposures, and longitudinally measured, correlated phenotypes are lacking. The purpose of our study was to demonstrate the utility of the structural equation modeling (SEM) approach to inform our understanding of the pathways by which genetic variants lead to disease risk. With the SEM method, we examine multiple pathways directly and indirectly through previously identified triglyceride (TG)-associated SNPs, methylation, and high-density lipoprotein (HDL), including sex, age, and smoking behavior, while adding in biologically plausible direct and indirect pathways. We observed significant SNP effects (P < 0.05 and directionally consistent) on TGs at visit 4 (TG4) for five loci, including rs645040 (DOCK7), rs964184 (ZPR1/ZNF259), rs4765127 (ZNF664), rs1121980 (FTO), and rs10401969 (SUGP1). Across these loci, we identify three with strong evidence of an indirect genetic effect on TG4 through HDL, one with evidence of pleiotropic effect on HDL and TG4, and one variant that acts on TG4 indirectly through a nearby methylation site.
    [Show full text]
  • New Genetic Loci Link Adipose and Insulin Biology to Body Fat Distribution
    Europe PMC Funders Group Author Manuscript Nature. Author manuscript; available in PMC 2015 August 12. Published in final edited form as: Nature. 2015 February 12; 518(7538): 187–196. doi:10.1038/nature14132. Europe PMC Funders Author Manuscripts New genetic loci link adipose and insulin biology to body fat distribution A full list of authors and affiliations appears at the end of the article. # These authors contributed equally to this work. Abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms. Europe PMC Funders Author Manuscripts Depot-specific accumulation of fat, particularly in the central abdomen, confers an elevated risk of metabolic and cardiovascular diseases and mortality1. An easily accessible measure of body fat distribution is waist-to-hip ratio (WHR), a comparison of waist and hip circumferences.
    [Show full text]
  • High Throughput Gene Expression Analysis Identifies Reliable Expression Markers of Human Corneal Endothelial Cells
    High Throughput Gene Expression Analysis Identifies Reliable Expression Markers of Human Corneal Endothelial Cells Zhenzhi Chng1, Gary S. L. Peh2, Wishva B. Herath3, Terence Y. D. Cheng1, Heng-Pei Ang2, Kah-Peng Toh2, Paul Robson3, Jodhbir S. Mehta2,4,5*, Alan Colman1* 1 A*STAR Institute of Medical Biology, Singapore, Singapore, 2 Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore, Singapore, 3 Genome Institute of Singapore, Singapore, Singapore, 4 Singapore National Eye Centre, Singapore, Singapore, 5 Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore Abstract Considerable interest has been generated for the development of suitable corneal endothelial graft alternatives through cell-tissue engineering, which can potentially alleviate the shortage of corneal transplant material. The advent of less invasive suture-less key-hole surgery options such as Descemet’s Stripping Endothelial Keratoplasty (DSEK) and Descemet’s Membrane Endothelial Keratoplasty (DMEK), which involve transplantation of solely the endothelial layer instead of full thickness cornea, provide further impetus for the development of alternative endothelial grafts for clinical applications. A major challenge for this endeavor is the lack of specific markers for this cell type. To identify genes that reliably mark corneal endothelial cells (CECs) in vivo and in vitro, we performed RNA-sequencing on freshly isolated human CECs (from both young and old donors), CEC cultures, and corneal stroma. Gene expression of these corneal cell types was also compared to that of other human tissue types. Based on high throughput comparative gene expression analysis, we identified a panel of markers that are: i) highly expressed in CECs from both young donors and old donors; ii) expressed in CECs in vivo and in vitro; and iii) not expressed in corneal stroma keratocytes and the activated corneal stroma fibroblasts.
    [Show full text]
  • Design of Gene Editing Assays
    ) ( (51) International Patent Classification: 92121 (US). MAHAJAN, Sudipta; 11Lowe Circle, Fram¬ C07D 403/12 (2006.01) A61K 31/5377 (2006.01) ingham, MA 01701 (US). C07D 413/12 (2006.01) A61K 31/5386 (2006.01) (74) Agent: ALI, Bashir, M. et al. ; Brinks Gilson & Lione, P.o. A61P 35/00 (2006.01) Cl 2N 15/10 (2006.01) Box 110285, Research Triangle Park, NC 27709 (US). A61K 31/506 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection av ailable) . AE, AG, AL, AM, PCT/US20 19/0 13783 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (22) International Filing Date: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 16 January 2019 (16.01.2019) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (25) Filing Language: English KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (26) Publication Language: English MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (30) Priority Data: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/618,598 17 January 2018 (17.01.2018) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: VERTEX PHARMACEUTICALS INCOR¬ (84) Designated States (unless otherwise indicated, for every PORATED [US/US]; 50 Northern Avenue, Boston, MA kind of regional protection available) .
    [Show full text]
  • Identification and Mechanistic Investigation of Recurrent Functional Genomic and Transcriptional Alterations in Advanced Prostat
    Identification and Mechanistic Investigation of Recurrent Functional Genomic and Transcriptional Alterations in Advanced Prostate Cancer Thomas A. White A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2013 Reading Committee: Peter S. Nelson, Chair Janet L. Stanford Raymond J. Monnat Jay A. Shendure Program Authorized to Offer Degree: Molecular and Cellular Biology ©Copyright 2013 Thomas A. White University of Washington Abstract Identification and Mechanistic Investigation of Recurrent Functional Genomic and Transcriptional Alterations in Advanced Prostate Cancer Thomas A. White Chair of the Supervisory Committee: Peter S. Nelson, MD Novel functionally altered transcripts may be recurrent in prostate cancer (PCa) and may underlie lethal and advanced disease and the neuroendocrine small cell carcinoma (SCC) phenotype. We conducted an RNASeq survey of the LuCaP series of 24 PCa xenograft tumors from 19 men, and validated observations on metastatic tumors and PCa cell lines. Key findings include discovery and validation of 40 novel fusion transcripts including one recurrent chimera, many SCC-specific and castration resistance (CR) -specific novel splice isoforms, new observations on SCC-specific and TMPRSS2-ERG specific differential expression, the allele-specific expression of certain recurrent non- synonymous somatic single nucleotide variants (nsSNVs) previously discovered via exome sequencing of the same tumors, rgw ubiquitous A-to-I RNA editing of base excision repair (BER) gene NEIL1 as well as CDK13, a kinase involved in RNA splicing, and the SCC expression of a previously unannotated long noncoding RNA (lncRNA) at Chr6p22.2. Mechanistic investigation of the novel lncRNA indicates expression is regulated by derepression by master neuroendocrine regulator RE1-silencing transcription factor (REST), and may regulate some genes of axonogenesis and angiogenesis.
    [Show full text]
  • Supplemental Figures
    Control #1 Control #2 Control #3 83972 #1 83972 #2 83972 #3 CFT073 #1 CFT073 #2 CFT073 #3 Log-intensity ratios (M-values) ratios Log-intensity Log-intensity averages (A-values) Supplemental Figure 1. MA-plots showing normalized raw data using cross- correlation. The data was found to be of high quality with high replicate correlation (correlation>0.98) and with no systematic bias. A 83972 B CFT073 Supplemental Figure 2. Inversely regulated gene networks generated by IPA. The five inversely regulated genes belonged to one functional network in which HSPA6, FOSB and RN7SK interact with TATA box binding protein (TBP), a general transcription factor required for RNA polymerase II activity. The ABU strain 83972 (A) suppressed FOSB and other genes in this network while the CFT073 strain (B) enhanced their expression. 83972 also suppressed RGS4, a negative regulator of G-protein-coupled receptor-induced signaling and IFIT1, a gene of the type I IFN signaling pathway essential for the antibacterial effector response. A No of affected Network genes Score Top functions genes BAIAP2, BANP, BRIX1, Caspase, CTNNB1, Cyclin A, DACH1, Infection Mechanisms, EMP1, EPHA4, FGFBP1, GADD45G, HES1, HIST2H2BE, IgG, Infectious Disease, IL12, Interferon α, Jnk, MAVS, MDM2, NFkB, NOD1, P38 MAPK, 51 24 Endocrine System PDCD4, PELI2, PEMT, Ras homolog, TFAP2A, TLR5, Development and TNFRSF10D, UBC, Ubiquitin, VANGL2, VARS, Vegf, ZC3HAV1 Function AHCTF1, AKR1C2, ALOX5AP, ARL4A, BAMBI, BAZ2B, Bcl9- Cbp/p300-Ctnnb1-Lef/Tcf, BRF2, CA9, Ca2+, CNN2, CRIP1, Small Molecule
    [Show full text]
  • Comprehensive Identification of Transposable Element Insertions
    ARTICLE https://doi.org/10.1038/s41467-021-24041-8 OPEN Comprehensive identification of transposable element insertions using multiple sequencing technologies Chong Chu 1, Rebeca Borges-Monroy 2,3, Vinayak V. Viswanadham 1, Soohyun Lee1, Heng Li1,4, ✉ ✉ Eunjung Alice Lee2,3 & Peter J. Park 1 1234567890():,; Transposable elements (TEs) help shape the structure and function of the human genome. When inserted into some locations, TEs may disrupt gene regulation and cause diseases. Here, we present xTea (x-Transposable element analyzer), a tool for identifying TE insertions in whole-genome sequencing data. Whereas existing methods are mostly designed for short- read data, xTea can be applied to both short-read and long-read data. Our analysis shows that xTea outperforms other short read-based methods for both germline and somatic TE insertion discovery. With long-read data, we created a catalogue of polymorphic insertions with full assembly and annotation of insertional sequences for various types of retroelements, including pseudogenes and endogenous retroviruses. Notably, we find that individual gen- omes have an average of nine groups of full-length L1s in centromeres, suggesting that centromeres and other highly repetitive regions such as telomeres are a significant yet unexplored source of active L1s. xTea is available at https://github.com/parklab/xTea. 1 Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 2 Division of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA. 3 Broad Institute of MIT and Harvard, Cambridge, MA, USA. 4 Department of Data Sciences, Dana-Farber Cancer ✉ Institute, Boston, MA, USA.
    [Show full text]
  • Transcriptional-Readthrough Rnas Reflect the Phenomenon of “A Gene Contains Gene(S)” Or “Gene(S) Within a Gene” in the H
    G C A T T A C G G C A T genes Review Transcriptional-Readthrough RNAs Reflect the Phenomenon of “A Gene Contains Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and Thus Are Not Chimeric RNAs Yan He 1,*, Chengfu Yuan 2,*, Lichan Chen 3, Mingjuan Lei 3, Lucas Zellmer 4, Hai Huang 5,* and Dezhong Joshua Liao 1,6,* 1 Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China in Guizhou Medical University, Guiyang 550004, Guizhou, China 2 Department of Biochemistry, China Three Gorges University, Yichang City 443002, Hubei, China 3 Hormel Institute, University of Minnesota, Austin, MN 55912, USA; [email protected] (L.C.); [email protected] (M.L.) 4 Masonic Cancer Center, University of Minnesota, 435 E. River Road, Minneapolis, MN 55455, USA; [email protected] 5 School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, Guizhou, China 6 Department of Pathology, Guizhou Medical University Hospital, Guiyang 550004, Guizhou, China * Correspondence: [email protected] (Y.H.); [email protected] (C.Y.); [email protected] (H.H.); [email protected] (D.J.L.) Received: 29 November 2017; Accepted: 7 January 2018; Published: 16 January 2018 Abstract: Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a true readthrough event still awaits more evidence and trans-splicing that joins two transcripts together remains as a possible mechanism.
    [Show full text]
  • Detecting Gene Modules Differentially Expressed in Multiple Human Brain
    Detecting Gene Modules Differentially Expressed in Multiple Human Brain Regions THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Zhiwei Ma Graduate Program in Biophysics The Ohio State University 2012 Master's Examination Committee: Dr. Kun Huang, Advisor Dr. Raghu Machiraju Copyright by Zhiwei Ma 2012 Abstract Molecular screen methods such as microarrays have been used to identify molecular signatures and biological processes important for particular neuronal functions. This thesis applied a weight gene co-expression network analysis algorithm, edge-covering Quasi-Clique Merger algorithm (eQCM), on human brain microarray data from the Allen Institute of Brain Science. One thousand and sixty-six (1066) gene modules were identified. Within these 1066 gene modules, using eigengene as the representation of each gene module, 46 gene modules with significant p-values were selected by comparing the gene expression profiles between the hippocampus, parahippocampal gyrus and basal ganglia in the human brain. Through gene ontology enrichment analysis, 10 out of these 46 gene modules are significantly engaged in several biological processes of neuronal functions. The results showed that the correlation between molecular similarities and spatial proximity still exists in some human brain regions other than the neocortex. ii Dedication This document is dedicated to my parents. iii Acknowledgments I would like to express my deep gratitude to my advisor, Dr. Kun Huang, for his excellent overall guidance during my stay at OSU. I would like to thank Dr. Raghu Machiraju for being my committee member and providing me many great revision suggestions for my thesis.
    [Show full text]
  • Genome-Wide Association Studies of Structural Birth Defects: a Review and Commentary
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Birth Defects Manuscript Author Res. Author Manuscript Author manuscript; available in PMC 2020 May 26. Published in final edited form as: Birth Defects Res. 2019 November 01; 111(18): 1329–1342. doi:10.1002/bdr2.1606. Genome-wide association studies of structural birth defects: A review and commentary Philip J. Lupo1, Laura E. Mitchell2, Mary M. Jenkins3 1Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas 2Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas 3National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia Abstract Background: While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have been relatively few genome-wide association studies (GWAS) of these conditions. We reviewed the current landscape of GWAS conducted for birth defects, noting novel insights, and future directions. Methods: This article reviews the literature with regard to GWAS of structural birth defects. Key defects included in this review include oral clefts, congenital heart defects (CHDs), biliary atresia, pyloric stenosis, hypospadias, craniosynostosis, and clubfoot. Additionally, other issues related to GWAS are considered, including the assessment of polygenic risk scores and issues related to genetic ancestry, as well as utilizing genome-wide single nucleotide polymorphism array data to evaluate gene–environment interactions and Mendelian randomization. Results: For some birth defects, including oral clefts and CHDs, several novel susceptibility loci have been identified and replicated through GWAS, including 8q24 for oral clefts, DGKK for hypospadias, and 4p16 for CHDs.
    [Show full text]