Genomic Instability And Chromosome Architecture. Kevin Mills, Ph.D. Associate Professor, The Jackson Laboratory

Size: px
Start display at page:

Download "Genomic Instability And Chromosome Architecture. Kevin Mills, Ph.D. Associate Professor, The Jackson Laboratory"

Transcription

1 Genomic Instability And Chromosome Architecture Kevin Mills, Ph.D. Associate Professor, The Jackson Laboratory

2 Genomic Instability is a Hallmark of Cancer Angiogenesis Invasion and Metastasis Metabolism Genomic Instability Perpetual Replication " Inflammation Resisting Apoptosis Evading Growth Inhibition Growth Signaling

3 Cancer Genomes Can Be Highly Aberrant and Variable Normal Genome Cancer Genome

4 Chromosome Lesions in Cancer acentric ring chromosome isochromosome pericentric inversion paracentric inversions reciprocal translocations Robertsonian translocations dicentric insertion deletion duplication double minute homogeneously staining region

5 Chromosome Lesions in Cancer acentric ring chromosome isochromosome pericentric inversion Abnormalities affecting a single chromosome paracentric inversions reciprocal translocations Robertsonian translocations dicentric Abnormalities affecting two or more chromosomes insertion deletion duplication double minute homogeneously staining region Copy number abnormalities

6 Genomic Instability The Good, The Bad, and The Ugly Tumor Initiation

7 Genomic Instability The Good, The Bad, and The Ugly Tumor Initiation Resistance and Relapse

8 Genomic Instability The Good, The Bad, and The Ugly Tumor Initiation Neoantigens Synthetic Lethality Resistance and Relapse

9 B-Cell Development and Transformation Germinal Center Immature B-cells AID AID Mature B-cells (memory, plasma) Somatic hypermutation Ig class switching

10 B-Cell Development and Transformation Germinal Center Immature B-cells AID AID Mature B-cells (memory, plasma) Somatic hypermutation Ig class switching GCB lymphoma ABC lymphoma myeloma

11 T(12;15) translocations involving IgH and c-myc in pro-b cell lymphomas from XRCC4 -/- p53 -/- mice! SKY! FISH for c-myc and IgH! c-myc! IgH! c-myc! IgH!

12 Complex Translocations and Gene Amplification! in NHEJ/p53 deficient pro-b cell Lymphomas! SKY! FISH! chromosome 12! chromosome 15! T162! IgH! c-myc! C(12;15)! C(15;12;6)! Chr. 12! T(12;15)! T(15;12;6)! Chr. 15! T(12;15)! T(15;12;6)! T554! -12! IgH! c-myc! C(12;15)! C(15;12;3)! Chr. 12! T(12;15)! T(15;12;3)! Chr. 15! T(12;15)! T(15;12;3)! Complicon! Complicon! Complicon! Zhu, et al. Cell 2002.

13 Chr. 12 IgH Chr. 15 c-myc c-myc c-myc c-myc c-myc IgH IgH IgH IgH 1. Why two translocated products from a single copy of Chr. 12? 2. Why not both copies of 12 and 15? 3. Why not other der(12) or der(15) translocations?

14 Chr. 12 IgH Chr. 15 c-myc c-myc c-myc c-myc c-myc IgH IgH IgH IgH Does proximity in the nucleus restrict possible translocation partners or function in target site selection? Does chromosome morphology influence tranlsocation susceptibility or function?

15 Chr. 12 IgH Chr. 15 c-myc c-myc c-myc c-myc c-myc IgH IgH IgH IgH Does proximity in the nucleus restrict possible translocation partners or function in target site selection? Does chromosome morphology influence tranlsocation susceptibility or function?

16 Nuclear Distribution of Chromosomes 12 and 15! Bone Marrow C57BL/6 Chr. 12 Chr. 15

17 Nuclear Distribution of Chromosomes 12 and 15! 2-D maximum intensity projection Manual Object Identification Bone Marrow Chr. 12 C57BL/6 Chr. 15

18 Nuclear Distribution of Chromosomes 12 and 15! 2-D maximum intensity projection Manual Object Identification Bone Marrow C57BL/6 Chr. 12 Chr. 15

19 Nuclear Distribution of Chromosomes 12 and 15! 2-D maximum intensity projection Manual Object Identification Bone Marrow C57BL/6 Chr. 12 Chr. 15

20 Nuclear Distribution of Chromosomes 12 and 15! 2-D maximum intensity projection: category frequencies Cat 1 Cat 2 Cat 3 Cat

21 Chromosome territory proximity relationships N= N= N=234 R G G R 5.2% (10) 7.0% (14) 7.7% (18) R R G G 12.4% (24) 18.0% (36) 15.8% (37) R G 79.9% (155) 69.5% (139) 69.7% (163) R G G R 2.6% (5) 5.5% (11) 6.8% (16)

22 Subcategories of heterologous proximal pairs R G G R R G R G G R R G R R G R G G

23 Subcategories of heterologous proximal pairs G R G R 44.5% 48.9% 39.9% R G 23.2% 11.5% 19.7% G R R G R G R G 32.3% 39.6% 40.4%

24 Nuclear Distribution of Chromosomes 12 and 15! Confocal Z-stack: 200nm step size Bone Marrow C57BL/6 Chr. 12 Chr. 15

25 Nuclear Distribution of Chromosomes 12 and 15! Confocal Z-stack: 3-D chromosome positioning Formaldehyde fixation Bone Marrow C57BL/6 Chr. 12 Chr. 15

26 We Needed a Better Approach to Image Analysis Objective Quantitative Sensitive Accurate High Throughput

27 Automated image segmentation and object identification! Wavelet-based multifractal analysis algorithm

28 Automated image segmentation and object identification! Objective analysis of image features A B A B D(A,B) = 0.0 D(A,A) = 15.0 D(A,B) = 29.4 D(B,B) = 39.8 D(A,B) = 65.8 D(A,B) = 87.2 Object Perimeter Diameter Area Filament Index Center of Mass A (89,87) B (157,99) A (152,71) B (186,161)

29 Automated image segmentation and object identification! Objective analysis of image features A B A B D(A,B) = 0.0 D(A,A) = 15.0 D(A,B) = 29.4 D(B,B) = 39.8 D(A,B) = 65.8 D(A,B) = 87.2 Object Perimeter Diameter Area Filament Index Center of Mass A (89,87) B (157,99) A (152,71) B (186,161)

30 Ultra high resolution 4Pi microscopy! Superior resolution in the Z axis Widefield Confocal 4Pi Y X X Z

THE DNA DSB RESPONSE : The. Role in IgH Class Switching and Suppression of Genomic Instability and Cancer

THE DNA DSB RESPONSE : The. Role in IgH Class Switching and Suppression of Genomic Instability and Cancer THE DNA DSB RESPONSE : The Role in IgH Class Switching and Suppression of Genomic Instability and Cancer GENERAL DSB REPAIR Via Non-Homologous End-Joining (NHEJ) DSBs IR, etc. DSB NHEJ NHEJ KNOWN NHEJ

More information

Chapter 14: Genes in Action

Chapter 14: Genes in Action Chapter 14: Genes in Action Section 1: Mutation and Genetic Change Mutation: Nondisjuction: a failure of homologous chromosomes to separate during meiosis I or the failure of sister chromatids to separate

More information

B cells Harry W Schroeder Jr MD PhD

B cells Harry W Schroeder Jr MD PhD B cells Harry W Schroeder Jr MD PhD Division of Clinical Immunology and Rheumatology Departments of Medicine, Microbiology, and Genetics University of Alabama at Birmingham Director, UAB Program in Immunology

More information

Higher Human Biology Unit 1: Human Cells Pupils Learning Outcomes

Higher Human Biology Unit 1: Human Cells Pupils Learning Outcomes Higher Human Biology Unit 1: Human Cells Pupils Learning Outcomes 1.1 Division and Differentiation in Human Cells I can state that cellular differentiation is the process by which a cell develops more

More information

Towards detection of minimal residual disease in multiple myeloma through circulating tumour DNA sequence analysis

Towards detection of minimal residual disease in multiple myeloma through circulating tumour DNA sequence analysis Towards detection of minimal residual disease in multiple myeloma through circulating tumour DNA sequence analysis Trevor Pugh, PhD, FACMG Princess Margaret Cancer Centre, University Health Network Dept.

More information

NUCLEOTIDE RESOLUTION STRUCTURAL VARIATION DETECTION USING NEXT- GENERATION WHOLE GENOME RESEQUENCING

NUCLEOTIDE RESOLUTION STRUCTURAL VARIATION DETECTION USING NEXT- GENERATION WHOLE GENOME RESEQUENCING NUCLEOTIDE RESOLUTION STRUCTURAL VARIATION DETECTION USING NEXT- GENERATION WHOLE GENOME RESEQUENCING Ken Chen, Ph.D. kchen@genome.wustl.edu The Genome Center, Washington University in St. Louis The path

More information

UAMS ADVANCED DIAGNOSTICS FOR ADVANCING CURE

UAMS ADVANCED DIAGNOSTICS FOR ADVANCING CURE UAMS ADVANCED DIAGNOSTICS FOR ADVANCING CURE advanced diagnostics for advancing cure Multiple myeloma (myeloma) is a complex cancer that can be diffcult to diagnose and challenging to treat. Every case

More information

Molecular Hematopathology Lymphomas. December 21, 2004

Molecular Hematopathology Lymphomas. December 21, 2004 Molecular Hematopathology Lymphomas December 21, 2004 Translocations Small or large fragment of a chromosome fuses with another chromosome The fusion is viable The fusion chromosome is faithfully replicated

More information

Elevated Immunoglobulins and Paraproteins

Elevated Immunoglobulins and Paraproteins Elevated Immunoglobulins and Paraproteins NWL Pathology GP Study Afternoon Thursday 19 th October 2017 Dr Aristeidis Chaidos Consultant Haematologist and Honorary Senior Clinical Lecturer Hammersmith Hospital,

More information

High content imaging and applications

High content imaging and applications High content imaging and applications Nick Dolman Ph.D. Senior Staff Scientist Biosciences Division- Thermo Fisher Scientific For Research Use Only. Not for use in diagnostic procedures. The world leader

More information

Research techniques in genetics. Medical genetics, 2017.

Research techniques in genetics. Medical genetics, 2017. Research techniques in genetics Medical genetics, 2017. Techniques in Genetics Cloning (genetic recombination or engineering ) Genome editing tools: - Production of Knock-out and transgenic mice - CRISPR

More information

GENES AND CHROMOSOMES II

GENES AND CHROMOSOMES II 1 GENES AND CHROMOSOMES II Lecture 4 BIOL 266/2 2014-15 Dr. S. Azam Biology Department Concordia University 2 GENE AND THE GENOME The Structure of the Genome DNA fingerprinting 3 DNA fingerprinting: DNA-based

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Figure 1. Defective T and B cell lineage development in the absence of 53BP1. a, Average number of thymocytes in WT, 53BP1 /, p53 /, 53BP1 / / p53, Nbs1 tr735 and 53BP1 / Nbs1 tr735 mice

More information

Problem Set 2B Name and Lab Section:

Problem Set 2B Name and Lab Section: Problem Set 2B 9-26-06 Name and Lab Section: 1. Define each of the following rearrangements (mutations) (use one phrase or sentence for each). Then describe what kind of chromosomal structure you might

More information

HEALTHTREE QUESTIONNAIRE

HEALTHTREE QUESTIONNAIRE HEALTHTREE QUESTIONNAIRE PLEASE ASK YOUR NURSE OR HEALTH CARE TEAM IF YOU NEED HELP COMPLETING THE FORM Name Date: PRIOR MYELOMA START STOP TYPE OF DID THE DOCTOR ADD OR REMOVE A DRUG OR CHANGE YOUR DOSE?

More information

Fluorescence in situ hybridization (FISH) Testing in Multiple Myeloma

Fluorescence in situ hybridization (FISH) Testing in Multiple Myeloma Fluorescence in situ hybridization (FISH) Testing in Multiple Myeloma William Bellamy, Ph.D., HCLD (ABB), CC (ABB) Arkansas Clinical Laboratory Management Association/ American Society for Clinical Lab

More information

Chromosomal Mutations. 2. Gene Mutations

Chromosomal Mutations. 2. Gene Mutations 12-4 12-4 1. Chromosomal 3. NOT! 2. Gene A genetic mutation is any change in the DNA nucleotide sequence. Mutation is caused by mistakes during DNA replication, as well as mutagens, like certain chemicals

More information

October 24, BIOS 95: Cell Division and Chromosome Dynamics

October 24, BIOS 95: Cell Division and Chromosome Dynamics October 24, 2008 BIOS 95: Cell Division and Chromosome Dynamics Cancer unregulated cell growth and migration Aneuploidy errors in chromosome segregation and genome maintenance living with an altered genome

More information

Mutations, Genetic Testing and Engineering

Mutations, Genetic Testing and Engineering Mutations, Genetic Testing and Engineering Objectives Describe how techniques such as DNA fingerprinting, genetic modifications, and chromosomal analysis are used to study the genomes of organisms (TEKS

More information

Antigen receptor (immunoglobulin and T-cell receptor) gene rearrangements: Utility in Routine Diagnostic Hematopathology

Antigen receptor (immunoglobulin and T-cell receptor) gene rearrangements: Utility in Routine Diagnostic Hematopathology Antigen receptor (immunoglobulin and T-cell receptor) gene rearrangements: Utility in Routine Diagnostic Hematopathology DIAGNÓSTICO PRÁTICO DOS LINFOMAS São Paulo, Brasil 02 DE SETEMBRO DE 2011 Adam Bagg

More information

Illumina Genome Analyzer. Progenika Experience. - Susana Catarino -

Illumina Genome Analyzer. Progenika Experience. - Susana Catarino - Illumina Genome Analyzer Progenika Experience - Susana Catarino - Who are we? 2000 PROGENIKA BIOPHARMA Development, production and commercialization of new genomic tools for diagnosis, prognosis and drug-response

More information

Cloning from plant cells

Cloning from plant cells Cloning plants, animals, and cells Take a cutting from a plant, put it in a pot of soil, and you have cloned an organism. The plant that grows from the cutting will be genetically identical to the one

More information

Chapter 5. Genetic Models. Organization and Expression of Immunoglobulin Genes 3. The two-gene model: Models to Explain Antibody Diversity

Chapter 5. Genetic Models. Organization and Expression of Immunoglobulin Genes 3. The two-gene model: Models to Explain Antibody Diversity Chapter 5 Organization and Expression of Immunoglobulin Genes 3 4 5 6 Genetic Models How to account for: ) Vast diversity of antibody specificities ) Presence of Variable regions at the amino end of Heavy

More information

GenASIs TM Cytogenetics Suite

GenASIs TM Cytogenetics Suite GenASIs TM Cytogenetics Suite FDA 510(k) cleared for the following GenASIs applications: ALK, BandView, FISHView, UroVysion, CEP XY & HER2/neu FISH per the description found on the back page of this booklet.

More information

Session 3 Lecture 1 Dynamics of the GIT Microbiome: Microbial Darwinism

Session 3 Lecture 1 Dynamics of the GIT Microbiome: Microbial Darwinism Session 3 Lecture 1 Dynamics of the GIT Microbiome: Microbial Darwinism 10 14 bacteria representing ~1000 species and many phyla live in a crowded ecological space: The GIT Four major phyla dominate: By

More information

Pei et al. Supplementary Figure S1

Pei et al. Supplementary Figure S1 Pei et al. Supplementary Figure S1 C H-CUL9: + + + + + Myc-ROC1: - - + + + U2OS/pcDN3 U2OS/H-CUL9 U2OS/ + H-CUL9 IP: -H -myc input -H -myc 1 2 3 4 5 H-CUL9 Myc-ROC1 -H -H -H -H H-CUL9: wt RR myc-roc1:

More information

Chapter 17 Lecture. Concepts of Genetics. Tenth Edition. Regulation of Gene Expression in Eukaryotes

Chapter 17 Lecture. Concepts of Genetics. Tenth Edition. Regulation of Gene Expression in Eukaryotes Chapter 17 Lecture Concepts of Genetics Tenth Edition Regulation of Gene Expression in Eukaryotes Chapter Contents 17.1 Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNA to Protein

More information

Philippe Hupé 1,2. The R User Conference 2009 Rennes

Philippe Hupé 1,2. The R User Conference 2009 Rennes A suite of R packages for the analysis of DNA copy number microarray experiments Application in cancerology Philippe Hupé 1,2 1 UMR144 Institut Curie, CNRS 2 U900 Institut Curie, INSERM, Mines Paris Tech

More information

Introduction to Microarray Analysis

Introduction to Microarray Analysis Introduction to Microarray Analysis Methods Course: Gene Expression Data Analysis -Day One Rainer Spang Microarrays Highly parallel measurement devices for gene expression levels 1. How does the microarray

More information

NGS-Based Clonality Testing Assessing Clonality Status, Somatic Hypermutation and Monitoring Minimum Residual Disease (MRD)

NGS-Based Clonality Testing Assessing Clonality Status, Somatic Hypermutation and Monitoring Minimum Residual Disease (MRD) NGS-Based Clonality Testing Assessing Clonality Status, Somatic Hypermutation and Monitoring Minimum Residual Disease (MRD) Maria Arcila, M.D. Memorial Sloan Kettering Cancer Center Educational Goals Review

More information

1 Name. 1. (3 pts) What is apoptosis and how does it differ from necrosis? Which is more likely to trigger inflammation?

1 Name. 1. (3 pts) What is apoptosis and how does it differ from necrosis? Which is more likely to trigger inflammation? 1 Name MCB 150 Midterm Eam #1 (100 points total) Please write your full name on each page of the eam!! The eam consists of 17 questions (6 pages). Each has a different point count as indicated. Please

More information

Cancer Genetics Solutions

Cancer Genetics Solutions Cancer Genetics Solutions Cancer Genetics Solutions Pushing the Boundaries in Cancer Genetics Cancer is a formidable foe that presents significant challenges. The complexity of this disease can be daunting

More information

CS273B: Deep Learning in Genomics and Biomedicine. Recitation 1 30/9/2016

CS273B: Deep Learning in Genomics and Biomedicine. Recitation 1 30/9/2016 CS273B: Deep Learning in Genomics and Biomedicine. Recitation 1 30/9/2016 Topics Genetic variation Population structure Linkage disequilibrium Natural disease variants Genome Wide Association Studies Gene

More information

Cytogenetics. Chromosome is composed of 2 identical structures. And there is a constriction which called the centromere.

Cytogenetics. Chromosome is composed of 2 identical structures. And there is a constriction which called the centromere. Cytogenetics This sheet contains just the extra notes of 1-56 slides Slide 3 Cytogenetics is the study of the cell genetics that involve number of the chromosomes, their structure, their function, and

More information

Fluorescent in-situ Hybridization

Fluorescent in-situ Hybridization Fluorescent in-situ Hybridization Presented for: Presented by: Date: 2 Definition In situ hybridization is the method of localizing/ detecting specific nucleotide sequences in morphologically preserved

More information

AQA Biology A-level Topic 8: The control of gene expression

AQA Biology A-level Topic 8: The control of gene expression AQA Biology A-level Topic 8: The control of gene expression Notes Mutations Mutations are changes in the sequence of nucleotides in DNA molecules. Types of mutations include: Insertion/deletion mutations

More information

Genetic Basis of Development & Biotechnologies

Genetic Basis of Development & Biotechnologies Genetic Basis of Development & Biotechnologies 1. Steps of embryonic development: cell division, morphogenesis, differentiation Totipotency and pluripotency 2. Plant cloning 3. Animal cloning Reproductive

More information

If today s lecture is perplexing, there is a useful film at

If today s lecture is perplexing, there is a useful film at 1 Roadmap Chromosome evolution: Inversion Transposition Fission and fusion If today s lecture is perplexing, there is a useful film at http://www.youtube.com/watch?v=zcnymmhlkaw 2 One-minute responses

More information

Unit 1 Human cells. 1. Division and differentiation in human cells

Unit 1 Human cells. 1. Division and differentiation in human cells Unit 1 Human cells 1. Division and differentiation in human cells Stem cells Describe the process of differentiation. Explain how differentiation is brought about with reference to genes. Name the two

More information

Landing Cyto System. Automated platform for GYN (compliant with The Bethesda System) and non-gyn cytology. Automated abnormal cell detection

Landing Cyto System. Automated platform for GYN (compliant with The Bethesda System) and non-gyn cytology. Automated abnormal cell detection Automated platform for GYN (compliant with The Bethesda System) and non-gyn cytology Landing Cyto System Automated abnormal cell detection Automation Intelligence Standardization FEATURE SUMMARY The Landing

More information

REVIEWS. Structural variation in the human genome

REVIEWS. Structural variation in the human genome REVIEWS Structural variation in the human genome Lars Feuk, Andrew R. Carson and Stephen W. Scherer Abstract The first wave of information from the analysis of the human genome revealed SNPs to be the

More information

Fluorescent In Situ Hybridization (FISH) Assay

Fluorescent In Situ Hybridization (FISH) Assay Fluorescent In Situ Hybridization (FISH) Assay 1 What is FISH 2 Probes 3 FISH Procedure 4 Application Definition, Principle and Sample Types The core of FISH technology A quick and simple FISH protocol

More information

Structural variation. Marta Puig Institut de Biotecnologia i Biomedicina Universitat Autònoma de Barcelona

Structural variation. Marta Puig Institut de Biotecnologia i Biomedicina Universitat Autònoma de Barcelona Structural variation Marta Puig Institut de Biotecnologia i Biomedicina Universitat Autònoma de Barcelona Genetic variation How much genetic variation is there between individuals? What type of variants

More information

1. An alteration of genetic information is shown below. 5. Part of a molecule found in cells is represented below.

1. An alteration of genetic information is shown below. 5. Part of a molecule found in cells is represented below. 1. An alteration of genetic information is shown below. 5. Part of a molecule found in cells is represented below. A-G-T-A-C-C-G-A-T A-G-T-G-A-T This type of alteration of the genetic information is an

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle   holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/22550 holds various files of this Leiden University dissertation. Author: Yan, Kuan Title: Image analysis and platform development for automated phenotyping

More information

Guidelines for the diagnosis of Multiple Myeloma Ass.lec.: Dr. Karam T. Agha M.Sc.Pathology

Guidelines for the diagnosis of Multiple Myeloma Ass.lec.: Dr. Karam T. Agha M.Sc.Pathology Guidelines for the diagnosis of Multiple Myeloma 2014 By:British Committee for Standards in Haematology (BCSH) Ass.lec.: Dr. Karam T. Agha M.Sc.Pathology Diagnosis, prognostic factors and disease monitoring

More information

Supplementary Figure 1. Xbp1 deficiency does not alter hematopoietic cellularity.

Supplementary Figure 1. Xbp1 deficiency does not alter hematopoietic cellularity. Supplementary Figure 1 Xbp1 deficiency does not alter hematopoietic cellularity. Absolute number of leukocytes obtained from bone marrow (BM, 2 tibias and 2 femurs per mouse) of Xbp1 f/f and Xbp1 Vav1

More information

Molecular Genetics of Disease and the Human Genome Project

Molecular Genetics of Disease and the Human Genome Project 9 Molecular Genetics of Disease and the Human Genome Project Fig. 1. The 23 chromosomes in the human genome. There are 22 autosomes (chromosomes 1 to 22) and two sex chromosomes (X and Y). Females inherit

More information

DNA life s code. Importance of DNA. DNA Structure. DNA Structure - nucleotide. DNA Structure nitrogen bases. Linking Nucleotides

DNA life s code. Importance of DNA. DNA Structure. DNA Structure - nucleotide. DNA Structure nitrogen bases. Linking Nucleotides Importance of life s code molecule that makes up genes and determines the traits of all living things Controls by: producing proteins Proteins are important because All structures are made of protein Skin

More information

Restrooms Cell phones on silent/vibrate. Refreshments. Patient resource materials

Restrooms Cell phones on silent/vibrate. Refreshments. Patient resource materials Restrooms Cell phones on silent/vibrate Refreshments Patient resource materials This presentation should not replace discussions with your healthcare provider, but seeks to provide information and resources

More information

Jumping Into Your Gene Pool: Understanding Genetic Test Results

Jumping Into Your Gene Pool: Understanding Genetic Test Results Jumping Into Your Gene Pool: Understanding Genetic Test Results Susan A. Berry, MD Professor and Director Division of Genetics and Metabolism Department of Pediatrics University of Minnesota Acknowledgment

More information

Immunogenetics. Immunodeficiency

Immunogenetics. Immunodeficiency 4.05.009 Immune response represents a system of recognition of foreign molecules. Immunogenetics Foreign molecules (proteins, glycoproteins, carbohydrates, ssdna, viruses) or parts of foreign molecules

More information

Biological consequences of site specific recombination: integration, excision, deletion

Biological consequences of site specific recombination: integration, excision, deletion Biological consequences of site specific recombination: integration, excision, deletion The types of DNA rearrangements promoted by a large number of site specific recombination systems and their physiological

More information

DNA & RNA. Chapter Twelve and Thirteen Biology One

DNA & RNA. Chapter Twelve and Thirteen Biology One DNA & RNA Chapter Twelve and Thirteen Biology One I. DNA Structure A. DNA monomers = nucleotides *1. sugar bonded to PO4 & one of four possible nitrogen bases 2. bases = Adenine, Guanine, Cytosine, Thymine

More information

UNIT MOLECULAR GENETICS AND BIOTECHNOLOGY

UNIT MOLECULAR GENETICS AND BIOTECHNOLOGY UNIT MOLECULAR GENETICS AND BIOTECHNOLOGY Standard B-4: The student will demonstrate an understanding of the molecular basis of heredity. B-4.1-4,8,9 Effective June 2008 All Indicators in Standard B-4

More information

Introduction to Basic Human Genetics. Professor Hanan Hamamy Department of Genetic Medicine and Development Geneva University Switzerland

Introduction to Basic Human Genetics. Professor Hanan Hamamy Department of Genetic Medicine and Development Geneva University Switzerland Introduction to Basic Human Genetics Professor Hanan Hamamy Department of Genetic Medicine and Development Geneva University Switzerland Training Course in Sexual and Reproductive Health Research Geneva

More information

GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY. Steven J. Norris, Ph.D

GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY. Steven J. Norris, Ph.D GENETIC BASIS OF ANTIBODY STRUCTURE AND DIVERSITY Steven J. Norris, Ph.D Topics I. General principles II. The heavy chain Ig locus and VDJ rearrangement III. Light chain rearrangement. IV. Mechanisms of

More information

بسم اهلل الرمحن الرحيم

بسم اهلل الرمحن الرحيم بسم اهلل الرمحن الرحيم Definition Multiple myeloma is a neoplastic plasma cell dyscrasia (PCD) that generally produced a monoclonal immunoglobulin protein, characterized by a clinical pentad: (a) anemia;

More information

Agilent NGS Solutions : Addressing Today s Challenges

Agilent NGS Solutions : Addressing Today s Challenges Agilent NGS Solutions : Addressing Today s Challenges Charmian Cher, Ph.D Director, Global Marketing Programs 1 10 years of Next-Gen Sequencing 2003 Completion of the Human Genome Project 2004 Pyrosequencing

More information

Genes are coded DNA instructions that control the production of proteins within a cell. The first step in decoding genetic messages is to copy a part

Genes are coded DNA instructions that control the production of proteins within a cell. The first step in decoding genetic messages is to copy a part Genes are coded DNA instructions that control the production of proteins within a cell. The first step in decoding genetic messages is to copy a part of the nucleotide sequence of the DNA into RNA. RNA

More information

From light microscopy to multi-photon imaging:

From light microscopy to multi-photon imaging: From light microscopy to multi-photon imaging: Old and novel approaches for systems biology Frederick Klauschen Program in Systems Immunology and Disease Modeling National Institutes of Health and Institute

More information

Analysis of structural variation. Alistair Ward USTAR Center for Genetic Discovery University of Utah

Analysis of structural variation. Alistair Ward USTAR Center for Genetic Discovery University of Utah Analysis of structural variation Alistair Ward USTAR Center for Genetic Discovery University of Utah What is structural variation? What differentiates SV from short variants? What are the major SV types?

More information

The CQ1 Confocal Quantitative Image Cytometer and its Application to Biological Measurement

The CQ1 Confocal Quantitative Image Cytometer and its Application to Biological Measurement The CQ1 Confocal Quantitative Image Cytometer and its Application to Biological Measurement Hirofumi Sakashita *1 Koji Ohashi *1 Kazuo Ozawa *2 ohei Tsubouchi *1 The CQ1 confocal quantitative image cytometer,

More information

The Nuclear Area Factor (NAF): a measure for cell apoptosis using microscopy and image analysis

The Nuclear Area Factor (NAF): a measure for cell apoptosis using microscopy and image analysis The Nuclear Area Factor (NAF): a measure for cell apoptosis using microscopy and image analysis Mark A. DeCoster Department of Biomedical Engineering and Institute for Micromanufacturing, Louisiana Tech

More information

Supplementary Figure S1. Immunodetection of full-length XA21 and the XA21 C-terminal cleavage product.

Supplementary Figure S1. Immunodetection of full-length XA21 and the XA21 C-terminal cleavage product. Supplementary Information Supplementary Figure S1. Immunodetection of full-length XA21 and the XA21 C-terminal cleavage product. Total protein extracted from Kitaake wild type and rice plants carrying

More information

Medical Cytogenetics. Jin Fan, Zhejiang University School of Medicine

Medical Cytogenetics. Jin Fan, Zhejiang University School of Medicine Medical Cytogenetics Jin Fan, jinfan@zju.edu.cn Zhejiang University School of Medicine 1. Chromatin and chromosome Chromatin in nucleus Euchromatin: Slightly and evenly stained, non- or low-repetitive

More information

Introduction to Genetics FALL 2018 EXAM II A) 12.5% B) 25 % C) 37.5% D) 50% E) 75%

Introduction to Genetics FALL 2018 EXAM II A) 12.5% B) 25 % C) 37.5% D) 50% E) 75% Introduction to Genetics FALL 2018 EXAM II Questions 1-3 refer to the following family. A male and female are both heterozygous for the autosomal recessive allele for albinism. They have four children.

More information

PV92 PCR Bio Informatics

PV92 PCR Bio Informatics Purpose of PCR Chromosome 16 PV92 PV92 PCR Bio Informatics Alu insert, PV92 locus, chromosome 16 Introduce the polymerase chain reaction (PCR) technique Apply PCR to population genetics Directly measure

More information

Mutations and the Birth and Death of Genes. Author Ann Brokaw Rocky River High School Ohio

Mutations and the Birth and Death of Genes. Author Ann Brokaw Rocky River High School Ohio Mutations and the Birth and Death of Genes Author Ann Brokaw Rocky River High School Ohio About This Activity These slides provide examples of different mutations and their effects on the organism and

More information

Einführung in die Genetik

Einführung in die Genetik Einführung in die Genetik Prof. Dr. Kay Schneitz (EBio Pflanzen) http://plantdev.bio.wzw.tum.de schneitz@wzw.tum.de Prof. Dr. Claus Schwechheimer (PlaSysBiol) http://wzw.tum.de/sysbiol claus.schwechheimer@wzw.tum.de

More information

LECTURE: 22 IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to:

LECTURE: 22 IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to: LECTURE: 22 Title IMMUNOGLOBULIN DIVERSITIES LEARNING OBJECTIVES: The student should be able to: Identify the chromosome that contains the gene segments that encode the surface immunoglobulin heavy chain

More information

Single Nucleotide Variant Analysis. H3ABioNet May 14, 2014

Single Nucleotide Variant Analysis. H3ABioNet May 14, 2014 Single Nucleotide Variant Analysis H3ABioNet May 14, 2014 Outline What are SNPs and SNVs? How do we identify them? How do we call them? SAMTools GATK VCF File Format Let s call variants! Single Nucleotide

More information

SEQUENCING. M Ataei, PhD. Feb 2016

SEQUENCING. M Ataei, PhD. Feb 2016 CLINICAL NEXT GENERATION SEQUENCING M Ataei, PhD Tehran Medical Genetics Laboratory Feb 2016 Overview 2 Background NGS in non-invasive prenatal diagnosis (NIPD) 3 Background Background 4 In the 1970s,

More information

DNA: Structure and Replication - 1

DNA: Structure and Replication - 1 DNA: Structure and Replication - 1 We have briefly discussed that DNA is the genetic molecule of life. In eukaryotic organisms DNA (along with its histone proteins) is found in chromosomes. All cell activities

More information

Practical Aspects of FISH 10/6/2015 NAHLA BAKHAMIS, MSC 1

Practical Aspects of FISH 10/6/2015 NAHLA BAKHAMIS, MSC 1 Practical Aspects of FISH NAHLA BAKHAMIS 10/6/2015 NAHLA BAKHAMIS, MSC 1 Outline What is FISH Types of probes Overview of the procedure Advantages and disadvantages of FISH Some FISH applications 10/6/2015

More information

Loss of Cul3 in Primary Fibroblasts

Loss of Cul3 in Primary Fibroblasts PSU McNair Scholars Online Journal Volume 5 Issue 1 Humans Being: People, Places, Perspectives and Processes Article 15 2011 Loss of Cul3 in Primary Fibroblasts Paula Hanna Portland State University Let

More information

T and B cell gene rearrangement October 17, Ram Savan

T and B cell gene rearrangement October 17, Ram Savan T and B cell gene rearrangement October 17, 2016 Ram Savan savanram@uw.edu 441 Lecture #9 Slide 1 of 28 Three lectures on antigen receptors Part 1 (Last Friday): Structural features of the BCR and TCR

More information

Chromosome Numbers in Bone Marrow Erythroid Cells of the

Chromosome Numbers in Bone Marrow Erythroid Cells of the CELL STRUCTURE AND FUNCTION 3, 8993 (1978) C by Japan Society for Cell Biology Chromosome Numbers in Bone Marrow Erythroid Cells of the Mouse, Rat and Rabbit Syoichi Yamashita, Shigeru Okada, Keiki Hayashi(Fang),

More information

Gene Expression. Chapters 11 & 12: Gene Conrtrol and DNA Technology. Cloning. Honors Biology Fig

Gene Expression. Chapters 11 & 12: Gene Conrtrol and DNA Technology. Cloning. Honors Biology Fig Chapters & : Conrtrol and Technology Honors Biology 0 Cloning Produced by asexual reproduction and so it is genetically identical to the parent st large cloned mammal: Dolly the sheep Animals that are

More information

GENE EXPRESSSION. Promoter sequence where RNA polymerase binds. Operator sequence that acts as a switch (yellow) OPERON

GENE EXPRESSSION. Promoter sequence where RNA polymerase binds. Operator sequence that acts as a switch (yellow) OPERON GENE EXPRESSSION 1 GENE REGULATION IN PROKARYOTES Bacteria can turn genes on or off depending on their environment Prokaryotes have operons clusters of related genes and regulatory sequences Promoter sequence

More information

Accelerating the Pace of Understanding

Accelerating the Pace of Understanding Vectra 3 P R O D U C T N O T E Quantitative Pathology Imaging and Analysis Key Benefits Part of PerkinElmer's Phenoptics workflow solution for Cancer Immunology Research Detect and measure multiple expressed

More information

GenASIs TM Cytogenetics Suite

GenASIs TM Cytogenetics Suite GenASIs TM Cytogenetics Suite Cytogenetic Booklet DOC000252 RevA - version for branding.indd 1 28-Dec-15 11:46:22 The Complete Platform The GenASIs TM Cytogenetics Suite is the most complete and effective

More information

DNA AND CHROMOSOMES. Genetica per Scienze Naturali a.a prof S. Presciuttini

DNA AND CHROMOSOMES. Genetica per Scienze Naturali a.a prof S. Presciuttini DNA AND CHROMOSOMES This document is licensed under the Attribution-NonCommercial-ShareAlike 2.5 Italy license, available at http://creativecommons.org/licenses/by-nc-sa/2.5/it/ 1. The Building Blocks

More information

Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability

Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability The Harvard community has made this article openly available. Please share

More information

DNA. Name: Class: Date: Multiple Choice Identify the choice that best completes the statement or answers the question.

DNA. Name: Class: Date: Multiple Choice Identify the choice that best completes the statement or answers the question. Class: Date: DNA Multiple Choice Identify the choice that best completes the statement or answers the question. 1. Which one of the following nucleotide pair bonds would be found in a DNA molecule? a.

More information

BIOL 2457 CHAPTER 3 Part 2 SI What is the function of the histone proteins that are part of DNA structure?

BIOL 2457 CHAPTER 3 Part 2 SI What is the function of the histone proteins that are part of DNA structure? BIOL 2457 HPER 3 Part 2 SI 1 1. What is the function of the histone proteins that are part of DN structure? 2. In transcription, acts as a template for synthesis. fter helicase unzips DN, what enzyme adds

More information

Chapter 8: DNA and RNA

Chapter 8: DNA and RNA Chapter 8: DNA and RNA Lecture Outline Enger, E. D., Ross, F. C., & Bailey, D. B. (2012). Concepts in biology (14th ed.). New York: McGraw- Hill. 1 8-1 DNA and the Importance of Proteins Proteins play

More information

Supplementary Materials for

Supplementary Materials for advances.sciencemag.org/cgi/content/full/4/9/eaat5401/dc1 Supplementary Materials for GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune

More information

Genome research in eukaryotes

Genome research in eukaryotes Functional Genomics Genome and EST sequencing can tell us how many POTENTIAL genes are present in the genome Proteomics can tell us about proteins and their interactions The goal of functional genomics

More information

Biology Milestone: Unit 3 Topics (Growth and Heridity)

Biology Milestone: Unit 3 Topics (Growth and Heridity) Biology Milestone: Unit 3 Topics (Growth and Heridity) Multiple Choice Identify the choice that best completes the statement or answers the question. 1. The diagram shows the DNA fingerprints from a blood

More information

Name Class Date. Practice Test

Name Class Date. Practice Test Name Class Date 12 DNA Practice Test Multiple Choice Write the letter that best answers the question or completes the statement on the line provided. 1. What do bacteriophages infect? a. mice. c. viruses.

More information

Mutations. Lecture 15

Mutations. Lecture 15 Mutations Lecture 15 Objectives 1: Mutation Define mutation. Describe the types of mutations and their effects on the protein that is produced Distinguishing between spontaneous and induced mutations.

More information

Solutions to Problem Set 6

Solutions to Problem Set 6 MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Name: Question 1 Solutions to 7.012 Problem Set 6 The

More information

Supplementary Figure 1. IFN-γ induces TRC dormancy. a, IFN-γ induced dormancy

Supplementary Figure 1. IFN-γ induces TRC dormancy. a, IFN-γ induced dormancy Supplementary Figure 1. IFN-γ induces TRC dormancy. a, IFN-γ induced dormancy of various tumor type TRCs, including H22 (murine hepatocarcinoma) and CT26 (murine colon cancer). Bar, 50 µm. b, B16 cells

More information

Targeted complete next generation sequencing and quality control of transgenes and integration sites in CHO cell line development

Targeted complete next generation sequencing and quality control of transgenes and integration sites in CHO cell line development Targeted Locus Amplification Technology Targeted complete next generation sequencing and quality control of transgenes and integration sites in CHO cell line development Cergentis B.V. Yalelaan 62 3584

More information

HaloPlex HS. Get to Know Your DNA. Every Single Fragment. Kevin Poon, Ph.D.

HaloPlex HS. Get to Know Your DNA. Every Single Fragment. Kevin Poon, Ph.D. HaloPlex HS Get to Know Your DNA. Every Single Fragment. Kevin Poon, Ph.D. Sr. Global Product Manager Diagnostics & Genomics Group Agilent Technologies For Research Use Only. Not for Use in Diagnostic

More information

Chapter 11: Applications of Biotechnology

Chapter 11: Applications of Biotechnology Chapter 11: Applications of Biotechnology Lecture Outline Enger, E. D., Ross, F. C., & Bailey, D. B. (2012). Concepts in biology (14th ed.). New York: McGraw- Hill. 11-1 Why Biotechnology Works 11-2 Biotechnology

More information

Overview of Immunohistochemistry

Overview of Immunohistochemistry Overview of Immunohistochemistry Immunohistochemistry (IHC) combines anatomical, immunological and biochemical techniques to identify discrete tissue components by the interaction of target antigens with

More information

ICSB Workshop: Drug Response Measurement and Analysis Part 2: Best practices for experimental design, execution, and analysis

ICSB Workshop: Drug Response Measurement and Analysis Part 2: Best practices for experimental design, execution, and analysis ICSB Workshop: Drug Response Measurement and Analysis Part 2: Best practices for experimental design, execution, and analysis Caitlin Mills Kartik Subramanian Drug-response experiments are becoming increasingly

More information

Histone Acetylation Controls the Inactive X Chromosome. Replication Dynamics

Histone Acetylation Controls the Inactive X Chromosome. Replication Dynamics Histone Acetylation Controls the Inactive X Chromosome Replication Dynamics Corella S. Casas-Delucchi 1,2,, Alessandro Brero 2,, Hans-Peter Rahn 2, Irina Solovei 3, Anton Wutz 4, Thomas Cremer 3, Heinrich

More information