GENETICS FOR DUMMIES
COURSE FOR PEOPLE who want to know more about genetics INTRODUCTION to BASIC GENETICS ANNEMIEKE VERKERK j.verkerk@erasmusmc.nl
First Day, Wednesday 1 November, room OWR-72 Moderators: Annemieke Verkerk & Robert Kraaij Time Speaker Subject 09.15-09.30 Registration and coffee 09.30-10.30 Annemieke Verkerk Basic genetics: history & concepts 10.30-10.45 Coffee break 10.45-11.45 Robert Kraaij Molecular genetics (1) 11.45-12.00 Coffee break 12.00-13.00 Robert Kraaij Molecular genetics (2) 13.00-13.45 Lunch 13.45-14.45 André Uitterlinden Introduction to complex genetics (1) 14.45-15.00 Coffee break 15.00-16.00 André Uitterlinden Introduction to complex genetics (2)
http://r2blog.com/r2s-picture-phun/
SOME HISTORY Photo Credit: The Warder Collection, NY
CHARLES DARWIN (1809-1882) UK 1859 : launched evolution theory _life evolves from one species to another _evolution is driven by natural selection _and characteristics can somehow be past on to next generations and change
Mendel (Austria) 1822 - 1884 1860 CHARACTERISTICS ARE TRANSMITTED
WHAT IS MENDELIAN INHERITANCE ? X bb BB X Bb Bb Bb Bb BB Bb Bb bb
SEARCH FOR THE “inheritance molecule” 1869 Friedrich Miescher (Switserland) 1878 Albrecht Kossel (Germany) 1919 Phoebus Levene (Litouwen, USA) 1928 Frederick Griffith (UK) 1927 Nikolai Koltsow (Russia) 1937 William Astbury (UK) 1943 Oswald Avery (Canada, USA) Colin MacLeod (Canada) Maclyn McCarty (USA) 1951 Linus Pauling (USA) 1952 Alfred Hershey, Martha Chase (USA) 1952 Rosalind Franklin, Maurice Wilkins (UK) 1953 Francis Crick, James Watson (USA)
X-RAY CRYSTALLOGRAPHY 1953 Rosalind Franklin Maurice Wilkins London’s King’s College: “DNA is a molecule in which two “strands” form a tightly linked pair”.
MODEL OF THE DNA DOUBLE HELIX Watson and Crick proposed: that the structure of DNA was a winding helix in which pairs of bases Adenine -- Thymine Guanine --- Cytosine held the two strands together. James Watson (age 25; still alive!) Francis Crick (age 36)
Publication of Watson and Crick in Nature in April 1953
http://www.flickr.com/photos/dullhunk/3965917511/sizes/m/in/photostream/ In 1962 Francis Crick, James Watson and Maurice Wilkins were awarded the Nobel Prize in Physiology or Medicine, for their discovery of the structure of DNA Rosalind Franklin, had passed away before then (1958).
SOME OTHER MILESTONES 1970 Discovery that DNA can be cleaved by Restriction Enzymes and isolation of the first restriction enzyme HindII Hamilton O. Smith (Nobel Prize Physiology/Medicine 1978) 1977 Development of the DNA Sanger sequencing method Fred Sanger (Nobel Prize Chemistry 1958) 1985 DNA can be replicated in vitro by Polymerase Chain Reaction – PCR Kary Mullis (Nobel Prize Chemistry 1993) 1989 Introduction of the term fingerprinting and use of DNA polymorphisms in paternity testing and murder cases…, using PCR Alec Jeffreys (Knighted by Queen Elizabeth in 1994) 1988-1989 Identification of the gene for Cystic Fribrosis on chromosome 7, the first disease gene identified by positional cloning Francis Collins and Lap-Chee Tsui 1990 Start Human Genome Project – sequence total human DNA 1998 first large scale detection of Single Nucleotide Polymorphisms (SNPs) using PCR and Sanger sequencing
SOME OTHER MILESTONES 1999 start of The SNP consortium: aim: to discover 300.000 SNPs in the human genome in two years result: described 1.4 million SNPs 2001-2003 Human Genome Project : from working draft to “finished” Sequence MAP 2002 start International HapMapProject: aim: investigate SNPs in populations 2005 Start publications on Population studies with Genome Wide Association Studies (GWAS) 2007 Start development techniques for Next Generation Sequencing 2010 First paper on gene finding with Next Generation Sequencing 2012 ENCODE project consortium: our junk DNA isn’t junk: many regulatory elements present 2011-2017 Development op Non-invasive prenatal testing = NIPT test 2014-2017 Clinical exome sequencing
HUMAN GENETICS BASICS
body some NUMBERS Cells in your body: 100.000.000.000.000 cells = 10 14 Cell nucleus: contains DNA consisting of chromosome pairs 23 Length of DNA in one nucleus: m 2 Genome: base pairs 3.000.000.000 = 3 x 10 9 codes for genes 22.000 http://www.turbosquid.com/3d-models/3d-human-body-cell-model/125447
THE GENOME = the entire genetic information of an organism stored in all chromosomes together, all genes (coding) + non-coding sequences , all basepairs chromosomes provided by Diane van Opstal and Laura van Zutven Clinical Genetics EMC
BUILD UP of a CHROMOSOME bases form pairs (G-C and A-T) DNA consist of 4 bases: A : adenine on a backbone of T : thymine _dexoyribose sugar G : guanine _phosphate groups C : cytosine 1. 2. 3. 4. 5. The complex of DNA and attached proteins in the cell nucleus = Chromatin = very tightly packed 2 sorts of chromatin (after G-banding coloring): Dark bands : Heterochromatin: very compact and not very active Light bands :Euchromatin: less compact and contains most genes and is active
KARYOGRAM All chromosomes in somatic cells are in pairs = 2n = diploid
TYPES OF CHROMOSOMES telomere p-arm short arm -p centromere q-arm long arm -q telomere Meta-centric Sub-metacentric Acro-centric Telo-centric arms equal length arms unequal not in humans length 12 1 4 13 mouse 7 16 2 5 14 19 17 3 8 15 20 18 6 9 21 X 10 22 Y 11
REPLICATION 1 pair sister chromatids homologous chromosomes
MITOSIS DIVISION OF SOMATIC CELLS https://www.khanacademy.org/science/biology/cellular-molecular-biology/mitosis/v/mitosis transcription occurs chromosomes have DNA is condense in “interphase” doubled (replication) (prophase) DNA less condensed genes are not transcribed = chromatin (S phase = synthesis Chromosomes line Sister chromatids are 2 new cells with up in the middle separated, are again normal chromosome (metaphase) independent chromosomes content (telophase) (anaphase)
MITOSIS DIVISION OF SOMATIC CELLS http://www.youtube.com/watch?v=AhgRhXl7w_g als wmv
MEIOSIS https://www.khanacademy.org/science/biology/cellular-molecular-biology/meiosis/v/comparing-mitosis-and-meiosis GERM CELL DIVISION Meiosis I: recombination between homologous chromosomes and separation of homologous chromosomes Meiosis II: separatio of the sisterchromatids
MEIOSIS GERM CELL DIVISION 1. recombination 2. pairs of chromosomes between homologous are separated chromosomes during production of germ cells chromosomes exchange pieces of DNA = recombination or crossing over to create genetic diversity 3. sister chromatids are separated
MEIOSIS DIVISION OF GERM CELLS https://www.youtube.com/watch?v=D1_-mQS_FZ0
STRUCTURE OF A GENE Consists of: a promoter region: binding of proteins for regulation 5’ UTR region : for stability of mRNA Exons: together code for a protein Introns: separate exons, are non coding 3’ UTR region: for stability of mRNA splice sites: on the exon-intron boundaries, sequense necessary for correct splicing out of introns Promoter Exon1 Intron1 Exon2 Intron2 Exon3 DNA 5’UTR AG GT………….…. AG G-T/A AG GT ………….…. AG G-T/A 3’UTR all exons from all 22.000 genes together are called the EXOME
FROM GENE TO PROTEIN Promoter Exon1 Exon2 Exon3 Intron1 Intron2 DNA GT………….…. AG 3’UTR 5’UTR GT ………….…. AG Transcription pre-mRNA Splicing mRNA Translation Protein amino acids
DNA versus RNA Deoxyribonucleic - Ribonucleic acid double strand - single strand stable - unstable OH H OH H Uracil CH 3 OH H H OH
GENE REGULATION methylation e from a distance p i g e n histon modification e t i c s http://www.roadmapepigenomics.org/
GENE METHYLATION AND EXPRESSION EXPLAINED WITH BEETHOVEN http://www.nature.com/news/epigenome-the-symphony-in-your-cells-1.16955
miRNA lncRNA 22 nt > 200 nt http://www.nature.com/nmeth/journal/v8/n5/pdf/nmeth0511-379.pdf pseudo genes http://www.pseudogene.org/
HUMAN GENETICS diseases
PHENOTYPE-GENOTYPE Phenotype : all physical and mental properties of an organism Genotype: the order and composition of your base pairs Your genotype largely determines your phenotype
HUMAN DISEASES CAUSED BY MISTAKES IN THE DNA INHERITED NEWLY ARISEN MUTATION DE NOVO MUTATION new mutation occurs in germ cell parent or arises in the early embryo
BASIC AIM IN HUMAN GENETICS TO FIND THE GENETIC CAUSE OF A HEREDITARY DISORDER MUTATION IN THE DNA ASSIGN A DEFINITE DIAGNOSIS ! connecting the phenotype with a genotype STUDY AND UNDERSTAND THE CAUSE OF DISEASE DEVELOP MEDICINE and/or TREATMENT CURE?? PREVENTION??
Recommend
More recommend
