Chromosomal Microarray Analysis in the Genetic Evaluation of 279
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Microdeletions in 16P11.2 and 13Q31.3 Associated with Developmental Delay and Generalized Overgrowth
Microdeletions in 16p11.2 and 13q31.3 associated with developmental delay and generalized overgrowth A.M. George1, J. Taylor2 and D.R. Love1 1Diagnostic Genetics, LabPlus, Auckland City Hospital, Auckland, New Zealand 2Northern Regional Genetic Service, Auckland City Hospital, Auckland, New Zealand Corresponding author: D.R. Love E-mail: [email protected] Genet. Mol. Res. 11 (3): 3133-3137 (2012) Received November 28, 2011 Accepted July 18, 2012 Published September 3, 2012 DOI http://dx.doi.org/10.4238/2012.September.3.1 ABSTRACT. Chromosome microarray analysis of patients with developmental delay has provided evidence of small deletions or duplications associated with this clinical phenotype. In this context, a 7.1- to 8.7-Mb interstitial deletion of chromosome 16 is well documented, but within this interval a rare 200-kb deletion has recently been defined that appears to be associated with obesity, or developmental delay together with overgrowth. We report a patient carrying this rare deletion, who falls into the latter clinical category, but who also carries a second very rare deletion in 13q31.3. It remains unclear if this maternally inherited deletion acts as a second copy number variation leading to pathogenic variation, or is non-causal and the true modifiers are yet to be determined. Key words: Developmental delay; Obesity; Overgrowth; GPC5; SH2B1 Genetics and Molecular Research 11 (3): 3133-3137 (2012) ©FUNPEC-RP www.funpecrp.com.br A.M. George et al. 3134 INTRODUCTION Current referrals for chromosome microarray analysis (CMA) are primarily for de- termining the molecular basis of developmental delay and autistic spectrum disorder in child- hood. -
Analysis of Trans Esnps Infers Regulatory Network Architecture
Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation. -
Ccdc80 and Ccdc80-L1: Identification and Functional Analysis of Two Novel Genes Involved in Zebrafish (Danio Rerio) Development
UNIVERSITÀ DEGLI STUDI DI MILANO SCUOLA DI DOTTORATO IN SCIENZE BIOLOGICHE E MOLECOLARI DIPARTIMENTO DI BIOLOGIA DOTTORATO DI RICERCA IN BIOLOGIA CELLULARE E MOLECOLARE XXIV CICLO ccdc80 and ccdc80-l1: Identification and Functional Analysis of Two Novel Genes Involved in Zebrafish (Danio rerio) Development settori scientifico/disciplinari: BIO/06; BIO/11 Tesi di dottorato di Chiara Brusegan R08215 TUTOR: prof. Franco Cotelli COORDINATORE DEL DOTTORATO: prof. Martino Bolognesi A.A. 2010/2011 Index Part I 1. Abstract 1 2. State of the art 2 2.1 Motility of the zebrafish embryo 2 2.2 Muscle formation 3 2.3 Neural differentiation 6 2.4 Identification of zebrafish ccdc80 genes 9 3. Aim of the project 13 4. Materials and Methods 14 4.1 Zebrafish lines and maintenance 14 4.2 Sequence analysis 14 4.3 RT-PCR 15 4.4 Synthesis of probes for whole mount in situ hybridization (WISH) 16 4.5 Whole-mount in situ hybridization 17 4.6 Immunohistochemistry 17 4.7 Histological sections 18 4.8 Injections 18 4.9 Cyclopamine treatment 19 4.10 Statistical analysis 19 5. Results 20 5.1 Identification of ccdc80 homologs in the genome of zebrafish 20 5.2.1 ccdc80 expression profiling 22 5.2.2 ccdc80-loss- and gain-of-function affects somitogenesis in vivo 23 5.2.3 ccdc80 is involved in somitogenesis, but not in the development of the notochord 25 5.2.4 ccdc80 is positively regulated by the Hedgehog pathway 26 5.3.1 ccdc80-l1 expression profiling 27 5.3.2 ccdc80-l1 knocked-down embryos displayed impaired motility 29 5.3.3 ccdc80-l1 loss of function does not affect somitogenesis nor muscle pioneers and adaxial cells formation 30 5.3.4 analysis of neurogenesis of primary motoneurons in ccdc80-l1 morphants 32 5.3.5 Also ccdc80-l1 expression is positively regulated by the Hedgehog pathway 35 5.4.1 ccdc80 expression is not regulated by ccdc80-l1, nor vice versa 37 6. -
Identification of the Binding Partners for Hspb2 and Cryab Reveals
Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-12-12 Identification of the Binding arP tners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non- Redundant Roles for Small Heat Shock Proteins Kelsey Murphey Langston Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Microbiology Commons BYU ScholarsArchive Citation Langston, Kelsey Murphey, "Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins" (2013). Theses and Dissertations. 3822. https://scholarsarchive.byu.edu/etd/3822 This Thesis is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston A thesis submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Master of Science Julianne H. Grose, Chair William R. McCleary Brian Poole Department of Microbiology and Molecular Biology Brigham Young University December 2013 Copyright © 2013 Kelsey Langston All Rights Reserved ABSTRACT Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactors and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston Department of Microbiology and Molecular Biology, BYU Master of Science Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity. -
Genome Sequence, Population History, and Pelage Genetics of the Endangered African Wild Dog (Lycaon Pictus) Michael G
Campana et al. BMC Genomics (2016) 17:1013 DOI 10.1186/s12864-016-3368-9 RESEARCH ARTICLE Open Access Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus) Michael G. Campana1,2*, Lillian D. Parker1,2,3, Melissa T. R. Hawkins1,2,3, Hillary S. Young4, Kristofer M. Helgen2,3, Micaela Szykman Gunther5, Rosie Woodroffe6, Jesús E. Maldonado1,2 and Robert C. Fleischer1 Abstract Background: The African wild dog (Lycaon pictus) is an endangered African canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. Results: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. Conclusions: We show that the African wild dog has undergone at least two effective population size reductions in the last 1,000,000 years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage. Keywords: Lycaon pictus, Genome, Population history, Selection, Pelage Background Primarily a hunter of antelopes, the African wild dog is a The African wild dog (Lycaon pictus) is an endangered highly distinct canine. -
Structural Forms of the Human Amylase Locus and Their Relationships to Snps, Haplotypes, and Obesity
Structural Forms of the Human Amylase Locus and Their Relationships to SNPs, Haplotypes, and Obesity The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Usher, Christina Leigh. 2015. Structural Forms of the Human Amylase Locus and Their Relationships to SNPs, Haplotypes, and Obesity. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467224 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Structural forms of the human amylase locus and their relationships to SNPs, haplotypes, and obesity A dissertation presented by Christina Leigh Usher to The Division of Medical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Genetics and Genomics Harvard University Cambridge, Massachusetts March 2015 © 2015 Christina Leigh Usher All rights reserved. Dissertation Advisor: Professor Steven McCarroll Christina Leigh Usher Structural forms of the human amylase locus and their relationships to SNPs, haplotypes, and obesity Abstract Hundreds of human genes reside in structurally complex loci that elude molecular analysis and assessment in genome-wide association studies (GWAS). One such locus contains the three different amylase genes (AMY2B, AMY2A, and AMY1) responsible for digesting starch into sugar. The copy number of AMY1 is reported to be the genome’s largest influence on obesity, yet has gone undetected in GWAS. -
Autism Multiplex Family with 16P11.2P12.2 Microduplication Syndrome in Monozygotic Twins and Distal 16P11.2 Deletion in Their Brother
European Journal of Human Genetics (2012) 20, 540–546 & 2012 Macmillan Publishers Limited All rights reserved 1018-4813/12 www.nature.com/ejhg ARTICLE Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother Anne-Claude Tabet1,2,3,4, Marion Pilorge2,3,4, Richard Delorme5,6,Fre´de´rique Amsellem5,6, Jean-Marc Pinard7, Marion Leboyer6,8,9, Alain Verloes10, Brigitte Benzacken1,11,12 and Catalina Betancur*,2,3,4 The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5–30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5–30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28–30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40–29.25 Mb), inherited from his apparently healthy father. -
Manual Annotation and Analysis of the Defensin Gene Cluster in the C57BL
BMC Genomics BioMed Central Research article Open Access Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome Clara Amid*†1, Linda M Rehaume*†2, Kelly L Brown2,3, James GR Gilbert1, Gordon Dougan1, Robert EW Hancock2 and Jennifer L Harrow1 Address: 1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK, 2University of British Columbia, Centre for Microbial Disease & Immunity Research, 2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada and 3Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden Email: Clara Amid* - [email protected]; Linda M Rehaume* - [email protected]; Kelly L Brown - [email protected]; James GR Gilbert - [email protected]; Gordon Dougan - [email protected]; Robert EW Hancock - [email protected]; Jennifer L Harrow - [email protected] * Corresponding authors †Equal contributors Published: 15 December 2009 Received: 15 May 2009 Accepted: 15 December 2009 BMC Genomics 2009, 10:606 doi:10.1186/1471-2164-10-606 This article is available from: http://www.biomedcentral.com/1471-2164/10/606 © 2009 Amid et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Host defense peptides are a critical component of the innate immune system. Human alpha- and beta-defensin genes are subject to copy number variation (CNV) and historically the organization of mouse alpha-defensin genes has been poorly defined. -
32-12012: Human Beta Defensin-3 Description Product
9853 Pacific Heights Blvd. Suite D. San Diego, CA 92121, USA Tel: 858-263-4982 Email: [email protected] 32-12012: Human Beta Defensin-3 Gene : DEFB103A Gene ID : 414325 Uniprot ID : P81534 Alternative Name : DEFB-3, Beta-defensin 3, Defensin, beta 103, Defensin-like protein Description Source: Genetically modified E.coli. Predicted MW: Monomer, 5.2 kDa (45 aa) Beta-Defensin 3 (BD-3), also known as DEFB-3, is a member of the defensin class of antimicrobial peptides. Beta defensins exert host defense responses against viruses, bacteria, and fungi through the binding and permeabilizing of microbial membranes. BD-3 expression is stimulated by interferon-gamma and is an important molecule during adaptive immunity. BD-3 functions to activate monocytes and mast cells, and has antibacterial functions towards Gram-negative and Gram-positive bacteria. Further, BD-3 blocks human immunodeficiency virus type 1 (HIV-1) replication through the downregulation of the HIV-1 co-receptor, CXCR4. Product Info Amount : 20 µg / 100 µg Purification : Reducing and Non-Reducing SDS PAGE at >= 95% Lyophilized from a sterile (0.2 micron) filtered aqueous solution containing 0.1% Trifluoroacetic Content : Acid (TFA) Sterile water at 0.1 mg/mL Storage condition : Store at -20°C Amino Acid : GIINTLQKYY CRVRGGRCAV LSCLPKEEQI GKCSTRGRKC CRRKK Application Note Endotoxin: Less than 0.1 ng/µg (1 IEU/µg) as determined by LAL test. Centrifuge vial before opening, Suspend the product by gently pipetting the above recommended solution down the sides of the vial. DO NOT VORTEX. Allow several minutes for complete reconstitution. For prolonged storage, dilute to working aliquots in a 0.1% BSA solution, store at -80°C and avoid repeat freeze thaws. -
Renal Cell Neoplasms Contain Shared Tumor Type–Specific Copy Number Variations
The American Journal of Pathology, Vol. 180, No. 6, June 2012 Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajpath.2012.01.044 Tumorigenesis and Neoplastic Progression Renal Cell Neoplasms Contain Shared Tumor Type–Specific Copy Number Variations John M. Krill-Burger,* Maureen A. Lyons,*† The annual incidence of renal cell carcinoma (RCC) has Lori A. Kelly,*† Christin M. Sciulli,*† increased steadily in the United States for the past three Patricia Petrosko,*† Uma R. Chandran,†‡ decades, with approximately 58,000 new cases diag- 1,2 Michael D. Kubal,§ Sheldon I. Bastacky,*† nosed in 2010, representing 3% of all malignancies. Anil V. Parwani,*†‡ Rajiv Dhir,*†‡ and Treatment of RCC is complicated by the fact that it is not a single disease but composes multiple tumor types with William A. LaFramboise*†‡ different morphological characteristics, clinical courses, From the Departments of Pathology* and Biomedical and outcomes (ie, clear-cell carcinoma, 82% of RCC ‡ Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania; cases; type 1 or 2 papillary tumors, 11% of RCC cases; † the University of Pittsburgh Cancer Institute, Pittsburgh, chromophobe tumors, 5% of RCC cases; and collecting § Pennsylvania; and Life Technologies, Carlsbad, California duct carcinoma, approximately 1% of RCC cases).2,3 Benign renal neoplasms are subdivided into papillary adenoma, renal oncocytoma, and metanephric ade- Copy number variant (CNV) analysis was performed on noma.2,3 Treatment of RCC often involves surgical resec- renal cell carcinoma (RCC) specimens (chromophobe, tion of a large renal tissue component or removal of the clear cell, oncocytoma, papillary type 1, and papillary entire affected kidney because of the relatively large size of type 2) using high-resolution arrays (1.85 million renal tumors on discovery and the availability of a life-sus- probes). -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
A Single-Cell Transcriptomic Landscape of Primate Arterial Aging
ARTICLE https://doi.org/10.1038/s41467-020-15997-0 OPEN A single-cell transcriptomic landscape of primate arterial aging Weiqi Zhang 1,2,3,4,5,13, Shu Zhang6,7,13, Pengze Yan3,8,13, Jie Ren7,9,13, Moshi Song3,5,8, Jingyi Li2,3,8, Jinghui Lei4, Huize Pan2,3, Si Wang3,5,8, Xibo Ma3,10, Shuai Ma2,3,8, Hongyu Li2,3, Fei Sun2,3, Haifeng Wan3,5,11, ✉ ✉ ✉ Wei Li 3,5,11, Piu Chan4, Qi Zhou3,5,11, Guang-Hui Liu 2,3,4,5,8 , Fuchou Tang 6,7,9,12 & Jing Qu 3,5,11 Our understanding of how aging affects the cellular and molecular components of the vas- 1234567890():,; culature and contributes to cardiovascular diseases is still limited. Here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize tran- scriptional landmarks that regulate vascular senility and position FOXO3A, a longevity- associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders. 1 CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.