Bayesian Hidden Markov Tree Models for Clustering Genes with Shared Evolutionary History
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Increased COUP-TFII Expression in Adult Hearts Induces Mitochondrial Dysfunction Resulting in Heart Failure
ARTICLE Received 9 Mar 2015 | Accepted 30 Jul 2015 | Published 10 Sep 2015 DOI: 10.1038/ncomms9245 OPEN Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure San-Pin Wu1,2, Chung-Yang Kao1, Leiming Wang1, Chad J. Creighton3,4, Jin Yang5, Taraka R. Donti6, Romain Harmancey7, Hernan G. Vasquez7, Brett H. Graham6,8, Hugo J. Bellen6,8, Heinrich Taegtmeyer7, Ching-Pin Chang5, Ming-Jer Tsai1,8 & Sophia Y. Tsai1,8 Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP- TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. 1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. 2 Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130, USA. -
Molecular Mechanism of ACAD9 in Mitochondrial Respiratory Complex 1 Assembly
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.07.425795; this version posted January 9, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Molecular mechanism of ACAD9 in mitochondrial respiratory complex 1 assembly Chuanwu Xia1, Baoying Lou1, Zhuji Fu1, Al-Walid Mohsen2, Jerry Vockley2, and Jung-Ja P. Kim1 1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA 2Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA Abstract ACAD9 belongs to the acyl-CoA dehydrogenase family, which catalyzes the α-β dehydrogenation of fatty acyl-CoA thioesters. Thus, it is involved in fatty acid β-oxidation (FAO). However, it is now known that the primary function of ACAD9 is as an essential chaperone for mitochondrial respiratory complex 1 assembly. ACAD9 interacts with ECSIT and NDUFAF1, forming the mitochondrial complex 1 assembly (MCIA) complex. Although the role of MCIA in the complex 1 assembly pathway is well studied, little is known about the molecular mechanism of the interactions among these three assembly factors. Our current studies reveal that when ECSIT interacts with ACAD9, the flavoenzyme loses the FAD cofactor and consequently loses its FAO activity, demonstrating that the two roles of ACAD9 are not compatible. ACAD9 binds to the carboxy-terminal half (C-ECSIT), and NDUFAF1 binds to the amino-terminal half of ECSIT. Although the binary complex of ACAD9 with ECSIT or with C-ECSIT is unstable and aggregates easily, the ternary complex of ACAD9-ECSIT-NDUFAF1 (i.e., the MCIA complex) is soluble and extremely stable. -
The Chemical Defensome of Fish: Conservation and Divergence of Genes Involved in Sensing and Responding to Pollutants Among Five Model Teleosts
The Chemical Defensome of Fish: Conservation and Divergence of Genes Involved in Sensing and Responding to Pollutants Among Five Model Teleosts Marta Eide University of Bergen Xiaokang Zhang Oslo University Hospital Odd André Karlsen University of Bergen Jared V. Goldstone Woods Hole Oceanographic Institution John Stegeman Woods Hole Oceanographic Institution Inge Jonassen University of Bergen Anders Goksøyr ( [email protected] ) University of Bergen Research Article Keywords: Chemical defensome, environmental contaminants, detoxication, nuclear receptors, biotransformation, antioxidant proteins, heat shock proteins, model species, toxicology Posted Date: February 9th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-175531/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License 1 The chemical defensome of fish: conservation and divergence of genes 2 involved in sensing and responding to pollutants among five model 3 teleosts. 4 5 Marta Eide1*, Xiaokang Zhang2,3*, Odd André Karlsen1, Jared V. Goldstone4, John Stegeman4, 6 Inge Jonassen2, Anders Goksøyr1§ 7 8 1. Department of Biological Sciences, University of Bergen, Norway 9 2. Computational Biology Unit, Department of Informatics, University of Bergen, Norway 10 3. Department of Molecular Oncology, Institute for Cancer Research, Oslo University 11 Hospital-Radiumhospitalet, Norway 12 4. Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA 13 14 * The authors contributed equally to the study 15 § Corresponding author: [email protected] 16 17 18 Abstract 19 20 How an organism copes with chemicals is largely determined by the genes and proteins that 21 collectively function to defend against, detoxify and eliminate chemical stressors. This 22 integrative network includes receptors and transcription factors, biotransformation enzymes, 23 transporters, antioxidants, and metal- and heat-responsive genes, and is collectively known 24 as the chemical defensome. -
Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma
Anatomy and Pathology Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma Sarah L. Lake,1 Sarah E. Coupland,1 Azzam F. G. Taktak,2 and Bertil E. Damato3 PURPOSE. To detect deletions and loss of heterozygosity of disease is fatal in 92% of patients within 2 years of diagnosis. chromosome 3 in a rare subset of fatal, disomy 3 uveal mela- Clinical and histopathologic risk factors for UM metastasis noma (UM), undetectable by fluorescence in situ hybridization include large basal tumor diameter (LBD), ciliary body involve- (FISH). ment, epithelioid cytomorphology, extracellular matrix peri- ϩ ETHODS odic acid-Schiff-positive (PAS ) loops, and high mitotic M . Multiplex ligation-dependent probe amplification 3,4 5 (MLPA) with the P027 UM assay was performed on formalin- count. Prescher et al. showed that a nonrandom genetic fixed, paraffin-embedded (FFPE) whole tumor sections from 19 change, monosomy 3, correlates strongly with metastatic death, and the correlation has since been confirmed by several disomy 3 metastasizing UMs. Whole-genome microarray analy- 3,6–10 ses using a single-nucleotide polymorphism microarray (aSNP) groups. Consequently, fluorescence in situ hybridization were performed on frozen tissue samples from four fatal dis- (FISH) detection of chromosome 3 using a centromeric probe omy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 became routine practice for UM prognostication; however, 5% years’ metastasis-free survival. to 20% of disomy 3 UM patients unexpectedly develop metas- tases.11 Attempts have therefore been made to identify the RESULTS. Two metastasizing UMs that had been classified as minimal region(s) of deletion on chromosome 3.12–15 Despite disomy 3 by FISH analysis of a small tumor sample were found these studies, little progress has been made in defining the key on MLPA analysis to show monosomy 3. -
The Genomic Structure and Expression of MJD, the Machado-Joseph Disease Gene
J Hum Genet (2001) 46:413–422 © Jpn Soc Hum Genet and Springer-Verlag 2001 ORIGINAL ARTICLE Yaeko Ichikawa · Jun Goto · Masahira Hattori Atsushi Toyoda · Kazuo Ishii · Seon-Yong Jeong Hideji Hashida · Naoki Masuda · Katsuhisa Ogata Fumio Kasai · Momoki Hirai · Patrícia Maciel Guy A. Rouleau · Yoshiyuki Sakaki · Ichiro Kanazawa The genomic structure and expression of MJD, the Machado-Joseph disease gene Received: March 7, 2001 / Accepted: April 17, 2001 Abstract Machado-Joseph disease (MJD) is an autosomal relative to the MJD gene in B445M7 indicate that there are dominant neurodegenerative disorder that is clinically char- three alternative splicing sites and eight polyadenylation acterized by cerebellar ataxia and various associated symp- signals in MJD that are used to generate the differently toms. The disease is caused by an unstable expansion of the sized transcripts. CAG repeat in the MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic structure, Key words Machado-Joseph disease (MJD) · 14q32.1 · we constructed a contig composed of six cosmid clones and CAG repeat · Genome structure · Alternative splicing · eight bacterial artificial chromosome (BAC) clones. It spans mRNA expression approximately 300kb and includes MJD. We also deter- mined the complete sequence (175,330bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240bp and to contain 11 exons. Northern Introduction blot analysis showed that MJD mRNA is ubiquitously expressed in human tissues, and in at least four different Machado-Joseph disease (MJD) is an autosomal dominant sizes; namely, 1.4, 1.8, 4.5, and 7.5kb. -
Replace This with the Actual Title Using All Caps
UNDERSTANDING THE GENETICS UNDERLYING MASTITIS USING A MULTI-PRONGED APPROACH A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Asha Marie Miles December 2019 © 2019 Asha Marie Miles UNDERSTANDING THE GENETICS UNDERLYING MASTITIS USING A MULTI-PRONGED APPROACH Asha Marie Miles, Ph. D. Cornell University 2019 This dissertation addresses deficiencies in the existing genetic characterization of mastitis due to granddaughter study designs and selection strategies based primarily on lactation average somatic cell score (SCS). Composite milk samples were collected across 6 sampling periods representing key lactation stages: 0-1 day in milk (DIM), 3- 5 DIM, 10-14 DIM, 50-60 DIM, 90-110 DIM, and 210-230 DIM. Cows were scored for front and rear teat length, width, end shape, and placement, fore udder attachment, udder cleft, udder depth, rear udder height, and rear udder width. Independent multivariable logistic regression models were used to generate odds ratios for elevated SCC (≥ 200,000 cells/ml) and farm-diagnosed clinical mastitis. Within our study cohort, loose fore udder attachment, flat teat ends, low rear udder height, and wide rear teats were associated with increased odds of mastitis. Principal component analysis was performed on these traits to create a single new phenotype describing mastitis susceptibility based on these high-risk phenotypes. Cows (N = 471) were genotyped on the Illumina BovineHD 777K SNP chip and considering all 14 traits of interest, a total of 56 genome-wide associations (GWA) were performed and 28 significantly associated quantitative trait loci (QTL) were identified. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
An Investigation Into the Genetic Architecture of Multiple System Atrophy and Familial Parkinson's Disease
An investigation into the genetic architecture of multiple system atrophy and familial Parkinson’s disease By Monica Federoff A thesis submitted to University College London for the degree of Doctor of Philosophy Laboratory of Neurogenetics, Department of Molecular Neuroscience, Institute of Neurology, University College London (UCL) 2 I, Monica Federoff, confirm that the work presented in this thesis is my own. Information derived from other sources and collaborative work have been indicated appropriately. Signature: Date: 09/06/2016 3 Acknowledgements: When I first joined the Laboratory of Neurogenetics (LNG), NIA, NIH as a summer intern in 2008, I had minimal experience working in a laboratory and was both excited and anxious at the prospect of it. From my very first day, Dr. Andrew Singleton was incredibly welcoming and introduced me to my first mentor, Dr. Javier Simon- Sanchez. Within just ten weeks working in the lab, both Dr. Singleton and Dr. Simon- Sanchez taught me the fundamental skills in an encouraging and supportive environment. I quickly got to know others in the lab, some of whom are still here today, and I sincerely appreciate their help with my assimilation into the LNG. After returning for an additional summer and one year as an IRTA postbac, I was honored to pursue a PhD in such an intellectually stimulating and comfortable environment. I am so grateful that Dr. Singleton has been such a wonderful mentor, as he is not only a brilliant scientist, but also extremely personable and approachable. If I inquire about meeting with him, he always manages to make time in his busy schedule and provides excellent guidance and mentorship. -
Proteomic and Metabolomic Analyses of Mitochondrial Complex I-Deficient
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 24, pp. 20652–20663, June 8, 2012 © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene*□S Received for publication, November 25, 2011, and in revised form, April 5, 2012 Published, JBC Papers in Press, April 25, 2012, DOI 10.1074/jbc.M111.327601 Dillon W. Leong,a1 Jasper C. Komen,b1 Chelsee A. Hewitt,a Estelle Arnaud,c Matthew McKenzie,d Belinda Phipson,e Melanie Bahlo,e,f Adrienne Laskowski,b Sarah A. Kinkel,a,g,h Gayle M. Davey,g William R. Heath,g Anne K. Voss,a,h René P. Zahedi,i James J. Pitt,j Roman Chrast,c Albert Sickmann,i,k Michael T. Ryan,l Gordon K. Smyth,e,f,h b2 a,h,m,n3 David R. Thorburn, and Hamish S. Scott Downloaded from From the aMolecular Medicine Division, gImmunology Division, and eBioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia, the bMurdoch Childrens Research Institute, Royal Children’s Hospital and Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia, the cDépartement de Génétique Médicale, Université de Lausanne, 1005 Lausanne, Switzerland, the dCentre for Reproduction and Development, Monash Institute of Medical Research, Clayton, Victoria 3168, Australia, the hDepartment of Medical Biology -
Original Article Bioinformatic Analysis of Gene Expression Profile in Prostate Epithelial Cells Exposed to Low-Dose Cadmium
Int J Clin Exp Med 2018;11(3):1669-1678 www.ijcem.com /ISSN:1940-5901/IJCEM0062792 Original Article Bioinformatic analysis of gene expression profile in prostate epithelial cells exposed to low-dose cadmium Qiling Liu1,2*, Rongqiang Zhang2*, Xiang Wang1, Peili Wang2, Xiaomei Ren2, Na Sun2, Xiangwen Li2, Xinhui Li2, Chunxu Hai1 1Department of Toxicology, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Op- erational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, Medical University of The Air Force, Xi’an, Shaanxi 710032, China; 2Department of Epidemic and Health Statis- tics, The College of Public Health for The Shaanxi University of Chinese Medicine, Shaanxi 712046, China. *Equal contributors. Received July 25, 2017; Accepted February 5, 2018; Epub March 15, 2018; Published March 30, 2018 Abstract: Objective: This study was to identify key genes and biological pathways involved in responses of prostate epithelial cells after low-dose Cd exposure by using bioinformatic analysis. Methods: The gene chip data of prostate epithelial cells after low-dose Cd exposure were collected from public databases Gene Expression Omnibus. After identification of differentially expressed genes (DEGs), data were input into Qlucore Omics Explorer, Network Analyst, String, and Genclip for further analysis of gene expression profiles, protein-protein interactions (PPI) and protein- chemicals interactions, and critical molecular pathways. Results: A total of 384 DEGs were identified in Cd treated group compared with control group. The number of DEGs gradually decreased over time, with the largest number at 0 h. Furthermore, NDUFB5 (A, S), CYC1, UQCRB, ETFA (B), SNRPD2, and LSM3 (5, 6) were the hub proteins in the PPI network. -
Low Abundance of the Matrix Arm of Complex I in Mitochondria Predicts Longevity in Mice
ARTICLE Received 24 Jan 2014 | Accepted 9 Apr 2014 | Published 12 May 2014 DOI: 10.1038/ncomms4837 OPEN Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice Satomi Miwa1, Howsun Jow2, Karen Baty3, Amy Johnson1, Rafal Czapiewski1, Gabriele Saretzki1, Achim Treumann3 & Thomas von Zglinicki1 Mitochondrial function is an important determinant of the ageing process; however, the mitochondrial properties that enable longevity are not well understood. Here we show that optimal assembly of mitochondrial complex I predicts longevity in mice. Using an unbiased high-coverage high-confidence approach, we demonstrate that electron transport chain proteins, especially the matrix arm subunits of complex I, are decreased in young long-living mice, which is associated with improved complex I assembly, higher complex I-linked state 3 oxygen consumption rates and decreased superoxide production, whereas the opposite is seen in old mice. Disruption of complex I assembly reduces oxidative metabolism with concomitant increase in mitochondrial superoxide production. This is rescued by knockdown of the mitochondrial chaperone, prohibitin. Disrupted complex I assembly causes premature senescence in primary cells. We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity. 1 Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. 2 Centre for Integrated Systems Biology of Ageing and Nutrition, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. 3 Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace, Newcastle upon Tyne NE1 7RU, UK. Correspondence and requests for materials should be addressed to T.v.Z. -
Mitochondrial Protein Quality Control Mechanisms
G C A T T A C G G C A T genes Review Mitochondrial Protein Quality Control Mechanisms Pooja Jadiya * and Dhanendra Tomar * Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA * Correspondence: [email protected] (P.J.); [email protected] (D.T.); Tel.: +1-215-707-9144 (D.T.) Received: 29 April 2020; Accepted: 15 May 2020; Published: 18 May 2020 Abstract: Mitochondria serve as a hub for many cellular processes, including bioenergetics, metabolism, cellular signaling, redox balance, calcium homeostasis, and cell death. The mitochondrial proteome includes over a thousand proteins, encoded by both the mitochondrial and nuclear genomes. The majority (~99%) of proteins are nuclear encoded that are synthesized in the cytosol and subsequently imported into the mitochondria. Within the mitochondria, polypeptides fold and assemble into their native functional form. Mitochondria health and integrity depend on correct protein import, folding, and regulated turnover termed as mitochondrial protein quality control (MPQC). Failure to maintain these processes can cause mitochondrial dysfunction that leads to various pathophysiological outcomes and the commencement of diseases. Here, we summarize the current knowledge about the role of different MPQC regulatory systems such as mitochondrial chaperones, proteases, the ubiquitin-proteasome system, mitochondrial unfolded protein response, mitophagy, and mitochondria-derived vesicles in the maintenance of mitochondrial proteome and health. The proper understanding of mitochondrial protein quality control mechanisms will provide relevant insights to treat multiple human diseases. Keywords: mitochondria; proteome; ubiquitin; proteasome; chaperones; protease; mitophagy; mitochondrial protein quality control; mitochondria-associated degradation; mitochondrial unfolded protein response 1. Introduction Mitochondria are double membrane, dynamic, and semiautonomous organelles which have several critical cellular functions.