lecture 1 Introduction.pptx medical labrotry

gentic molecular biology

1. Lecture 1: Introduction to Molecular diagnostics Program: Master of Clinical Laboratory Sciences (Molecular Diagnostics) Course: Principle of molecular and cellular biology

2. History of molecular biology Central dogma of Molecular biology Epigenetics Bioinformatics Application Content

3. Objectives Describe the concept of molecular biology Explain how the cells organize their DNA inside the nucleus and replicate it during cell division.

4. Introduction 1- Definition of Molecular Biology: is the branch of biology that deals with molecular basis of biological activity. It overlaps with other fields such as, Biology, genetics and biochemistry. 2- Molecular biology: The branch of biology that deals with the formation, structure, and function of macromolecules essential to life, such as nucleic acids and proteins.

5. History of Molecular Biology 1865 – Gregor Mendel published his work on laws of inheritance – dominance, segregation, and independent assortment) 1910 – Thomas H Morgan provided evidence for the chromosome theory of inheritance – i.e. chromosomes carry genes.

6. History of Molecular Biology 1929 – Phoebus Levene identified the components (the four bases, the sugar and the phosphate chain) and he showed that the components of DNA were linked in the order phosphate-sugar-base. 1940 – George Beadle and Edward Tatum demonstrated the existence of a precise relationship between genes and proteins . 1944 – Oswald Avery demonstrated that genes are made up of DNA .

7. History of Molecular Biology 1952  – Alfred Hershey and Martha Chase confirmed that the genetic material of the bacteriophage , the virus which infects bacteria, is made up of DNA . 1953  – James Watson and Francis Crick discovered the double helical structure of the DNA molecule. 1957  – Crick laid out the “Central Dogma” , which foretold the relationship between DNA, RNA, and proteins, and articulated the “sequence hypothesis.” 1958  – Meselson-Stahl experiment proves that DNA replication was semiconservative , a critical confirmation of the replication mechanism that was implied by the double-helical structure.

8. History of Molecular Biology 1961  – Francois Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA . 1961  – The genetic code was deciphered. Crick and Brenner identified the triplet codon pattern , while Marshall Nirenberg and Heinrich J. Matthaei cracked the codes for the first 54 out of the 64 codons .

9. The central dogma of molecular biology

10. Structure of nucleic acid Nucleic acid either DNA or RNA is long chain polymers of small chemical compound called nucleotides . Nucleotides are ring shaped compounds composed of: Nitrogenous base: classified into: Purine: double ringed structure (Adenine and Guanine). Pyrimidine: single ring structures (cytosine, thymine and uracil). Sugar Phosphate group

11. DNA Structure Deoxyribonucleic Acid (DNA): contain the structural blueprint for all the genetic instructions that is responsible for preserving, copying and transmitting information within cells and from generation to generation. It is a double strand ( α –helix) that twisted around each other, and move in opposite direction (antiparallel) and stabilized by hydrogen bonds. Each strand has a 5’ end (free phosphate group) and a 3’-end (free –HO). The sugar-phosphate backbones on the outside and base pairs on the inside. Nuclleotides are linked by phosphodiester bonds.

12. DNA packaging: Nuclear DNA molecules complexed with other proteins (nucleoprotein), to form a complex structure (chromatin) which allow some configurations of the DNA and types of control that are unique for the eukaryotic system

13. Nucleosomes They are condensed several times to form the intact chromatids.

14. Chromatin It consists of very long DNA molecules nearly an equal mass of rather small basic protein termed histone as well as small amount of non histone proteins and small quantity of RNA. Histone: heterogeneous group rich of arginine and lysine proteins. Which together make up fourth amino acid residue. These proteins are positively charged which allow them to bind tightly to the negatively charged sugar phosphate backbone of the DNA. Functionally, histones provide for the compaction of the chromatin.

15. RNA 1- RNA (ribonucleic acid) is a single stranded. 2- The pyrimidine thymine replaced by uracil (U) and ribose sugar replaces deoxyribose.

16. RNA types: There are three major classes of RNA: Messenger (mRNA) Transfer ( tRNA ) Ribosomal ( rRNA ). Minor classes of RNA include small nuclear RNA

17. mRNA: is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the process of transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). Subsequently, RNA processing mechanisms remove introns and keep exons in the mature mRNA transcript.

18. mRNA The primary mRNA undergoes three processes to give mature mRNA: Splicing: removal of noncoding sequence. Capping: addition of 7 methyl-guanosine triphosphate to 5' terminus. Addition of poly (A) tail: involves cleavage of its 3' end and then the addition of about 200 adenine residues.

19. rRNA It is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. Ribosome is the factory for protein synthesis, composed of ribosomal RNA and ribosomal proteins (known as a ribonucleoprotein or RNP). rRNA is a ribozyme which carries out protein synthesis in ribosomes.

20. tRNA It is an adaptor molecule that provides the physical link between the genetic code in messenger RNA (mRNA) and the amino acid sequence of proteins, carrying the correct sequence of amino acids to be combined by the protein-synthesizing machinery, the ribosome.

21. Protein Also known as polypeptide , are made of amino acid and arranged in a linear chain and folded into globular form.

22. Gene expression Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein. It consists of 2 processes: Transcription: Transcription is when the DNA in a gene is copied to produce an RNA transcript called mRNA Translation: Translation occurs after the messenger RNA (mRNA) has carried the transcribed ‘message’ from the DNA to protein-making factories in the cell, called ribosomes.

23. Transcription Location=nucleus. The information found in a gene in DNA is transcribed into an mRNA molecule RNA polymerase II (eukaryotic) binds to the gene’s promoter leading to DNA unwinds. RNA polymerase II adds the complementary RNA nucleotides. Transcription proceeds until the RNA polymerase II reaches a a sequence called terminators which signal that RNA transcription is complete. Both RNA polymerase II and mRNA detached. The DNA strand will twist back up.

24. RNA processing reaction: In eukaryotes, the primary RNA transcript of a gene needs further processing before it can be translated. This step is called “RNA processing”. Also, it needs to be transported out of the nucleus into the cytoplasm. Steps in RNA processing: Add a cap to the 5’ end. Add a poly-A tail to the 3’ end. splice out introns

25. Translation: Location: ribosomes the mRNA is "read" according to the genetic code, which relates the DNA sequence to the amino acid sequence in proteins

26. Epigenetics Epigenetics is the study of heritable changes in gene expression that are not encoded in the DNA of the genome. Epigenetics changes are linked to oncogenesis, progression and treatment of cancer , the regulation of development and function of the nervous system , gene regulation , cellular stress events , nutrigenomics , aging and DNA repair

27. Bioinformatics: Bioinformatics is an interdisciplinary field that develops algorithms and improves upon methods for storing, retrieving, organizing and analyzing biological data. A major activity in bioinformatics is to develop software tools to generate useful biological knowledge.

28. Applications: Genotyping Research Diagnosis Transplantation Detection of mutations Drug design identifying abnormalities in human and forensic medicine.

29. Thank you