1. Dr. Faisal Al-AllafAssistant Professor of Geneticsand Molecular MedicineUmm Al-Qura University Faculty ofMedicine, Makkah, Saudi Arabiafallaf@uqu.edu.saTel/Fax: 5270000 Ext: 4198The Cellular andMolecular Basisof Inheritance1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 1

2. . . . . :http://el.uqu.edu.sa/jusur/index.php?un_id=uqu :http://www.uqu.edu.sa/faallaf 72/30/1341Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa2 3. Course contents (syllabus)GENOME, TRANSCRIPTOME, AND PROTEOMECell, DNA and RNAGenome organization, gene structure and genetic codesCell Cycle and DNA replicationTranscription and post-transcriptional modificationTranslation and post-translational modificationCHROMOSOMES AND CELL DIVISIONChromosomes morphology and classificationCell cycle divisionMitosisMeiosis1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 3 4. Haploid and Diploid cellsThe cell is the basic functional component ofthe body (the unit of life), we are made up ofcells. The cells consists mostly ofcarbohydrates, lipids, proteins, and nucleicacids.The zygote is a stem cell (diploid) which candifferentiate into multiple linage. It is madeup of integration of two haploid cells; onefrom the father (Sperm) and one from themother (Egg)Gene is the basic unit of inheritance. Genesare coded massages written into anenormously long molecule called DNA.Comparing genomes amongspeciesreveals(unificationof thecreator)evolutionary relatedness.1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 4 5. What is genetics?Genetics can be considered atthe levels of DNA, genes,chromosomes, genomes, cells,tissue,organs,individuals,families, and populationsGenetics isthe studyofinheritanceDuring embryonic developmentcells in different parts of thebody become exposed todifferent influencesandacquired divergent properties,as they express differentcombinations of the >30000gene pairs they each contain1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 5 6. DNA makes RNA makes ProteinGenome is the complete set ofgenetic instructions in the cell ofa particular type of organismincluding nuclear andmitochondrial DNATranscriptome is the entiremRNA content of a cellProteome is the collection offunctioning proteins synthesizedby a living cell1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 6 7. Genomic DNA The zygote is a stem cell Both somatic cells and zygote contain the same DNA but their gene expression profile are different Genome is a genetic content of a cell includingnuclear and mitochondrial DNA The human genome project is a major international collaborative effort to map and sequence the entire human genome1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 7 8. Chromosomes The DNA is distributed between 23 pairs of homologous chromosomes. Of these, 23 chromosomes came through our mothers egg and 23 came through our fathers sperm A normal sperm contain 22autosomes (chromosome that does not have agene that determines sex) and one (either Xor Y) sex chromosome. A normal egg contain 22autosomes and one sex chromosome (always X). A normal female has 44 autosomes and two XX sex chromosomes. A normal male also has 46 chromosomes, but in place of one X is a much smaller Y, that carries gene(s) responsible for triggering male development. Each chromosome is made of two sister chromatids, which are held together by the centromere.1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 8 9. Genes are coded massages written intoan enormously long molecule called DNAA typical nucleus contains around 2m ofDNA divided unequally between 46chromosomesPrior cell division this is reduced to lessthan 5um by interact coiling and packingGenetics is the study of inheritance andhow traits are passed from one generationto the next or from parents to the offspringGene is the unit of inheritance. Genes aremade up of DNA and contain instructionsfor making a specific protein1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 9 10. The amount of A equals that of T and theamount of C equals that of GBase pairing involve the formation ofhydrogen bonds between the twocomplementary strands of DNA inwhich A always pairs with T and Galways pairs with C. Thus, %GC=%G + %C, if 42% GC {G 21%, C21%, A 29%, and T 29%}A-T base pairs have two connectinghydrogen bonds; G-C base pairshave threeWhat is important about basepairing?Can predict sequence of one strandbased on the sequence of the other.Replication and TranscriptionRepair of damaged DNA1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 10 11. Phosho-diester link between 3-OH ofribose and 5 phosphate of next nucleotide The backbone of each chain is formed by phosphodiester bonds between the 3 and 5 carbons of adjacent sugars. The two chains being held together by hydrogen bonds between the nitrogenous bases which point in towards the centre of the helix, forming base pairs (bp). The DNA chain end terminated by the 5 carbon atom of the sugar molecule is referred to as the 5 end (5 prime), and the end terminated by the 3 carbon atom is called the 3 end (3 prime). In the DNA duplex the 5 end of one strand is opposite the 3 end of the other.1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 11 12. The structure of DNAEach chromosome is composed of an extremely long molecule of DNAcomplexes with proteins and RNA to form a substance known as chromatinThe unit of length of DNA is the base pair (bp) and 1kilobase (1kb) gives1000bpThe lightly stained region of the DNA called euochromatin (GC rich (R band),transcriptionally active) and the dark stained region of the DNA calledheterochromatin (AT rich (G band), transcriptionally inactive)1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 12 13. The structure of nucleotide DNA consists of polymer of nucleotides within two interlinked, coiled chains called DNA. A nucleotide is a phosphorylated nucleoside. Each unit of purine (A and G) or pyrimidine (T and C) base together with one attached deoxyribose sugar and one phosphate group constitute a nucleotide Each nucleotide contains one of four bases and it is the sequence of these bases that contains the coded instructions There are two types of nitrogenous bases; the purines are adenine (A) and guanine (G) and the pyrimidines are thymine (T), cytosine (C) and uracil (U). Uracil presents in the RNA only1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 13 14. DNA: the hereditary material Nucleic acid is composed of a long chain of individual molecules called nucleotides Each nucleotide is composed of nitrogenous base,a sugar moleculeand aphosphate molecule Each base on one chain is matched by a complementary partner on the other and each sequence provides a template for synthesis of a copy of the other1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 14 15. DNA and RNARNA is present in both the cytoplasm and in particularly high concentrations inthe nucleolus of the nucleus.DNA is found mainly in the nucleus and mitochondria.In the Ribonucleic acid (RNA), the carbon atom at position 2 of the ribose sugarcontain a hydroxyl group.In the Deoxyribonucleic acid (DNA) in which the hydroxyl group at the position 2of the ribose sugar is replaced by a hydrogen, i.e. an oxygen molecule is lost.1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa15 16. Comparison between DNA and RNAThere are two types of Nucleic acids. DNA exists as twostrands, twisted together into a right handed helix, calledthe double helix. Each strand is a polymer of repeating unitscalled nucleotides.Feature DNARNADeoxyribose at the position 2Sugar of the ribose sugar RiboseBase pairingA-T and G-CA-U and G-C Single strandedStructure Double helix structureStrand length Long ShortCarries protein-encodingMaintain RNA-, andinformation andprotein-encodingcontrols howFunctioninformation.information is used.DNA cannot function asRNA can function as anan enzyme 1431/03/27enzyme Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 16 17. DNA coiling and packaging1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 17 18. 1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 18 19. 1431/03/27 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 19 20. References and Private Reading These slides are only a handout and the students must read the text book (Emerys element of medical genetics)1. Emerys Elements of Medical Genetics, 13th edition 2007, by Peter TURNPENNY and Sian ELLARD. Churchill Livingstone ELSEVIER. ISBN: 978-0-7020-2917-22. Medical Genetics at a Glance, 2nd edition 2008, by Dorian PRITCHARD and Bruce KORF. Blackwell Publishing. ISBN: 978-1-4051-4846-73. Genetics for Dummies, 2005, by Tara Robinson, Wiley Publishing, Inc. ISBN: 978-0-7645-9554-74. Cell Biology and Genetics, Crash Course, 2nd edition 2006, by Manson, Jones, Morris, Michael STEEL and Dan HORTON-SZAR. MOSBY ELSEVIER. ISBN: 0-7234-3248-15. Human Molecular Genetics, 3rd edition, 2003, by STRACHAN T. and A. READ. Garland science/Taylor and Francis group. ISBN: 978-0-8153-4182-66. Genomes, 3rd edition 2006, by T.A. BROWN. Garland science, ISBN: 978-0- 8153-4138-31431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa20 21. Acknowledgments For the providers of all the educational materials (video clips, pictures, diagrams and charts) including publishers, pharmaceutical companies or unknown internet users who made their material available for use, in this and other presentations, I offer heartfelt thanks and deep appreciation. I feel particularly grateful to faculty, staff, and our brilliant students who provided a unique intellectual and wonderful environment for work.1431/03/27Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 21