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Molecular Genetics Genetics, GEN 301

Molecular Genetics Genetics, GEN 301. Genetics Molecular. A A. Abugabal. GEN 301. The Aims of the course . Acquire the students with good basic grounding in the molecular structure, organization and function of genetic material

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Molecular Genetics Genetics, GEN 301

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  1. Molecular Genetics Genetics, GEN 301

  2. Genetics Molecular A A. Abugabal GEN 301

  3. The Aims of the course • Acquire the students with • good basic grounding in the molecular structure, organization and function of genetic material • To distiguish between different types of molecular markers • To critically appraise the different methods used in molecular mapping • To study the application of genetic analysis in different organisms

  4. Assessment Details: Assessment Details

  5. Introduction • The history of genetics is quite extensive. • It has taken the work of many brilliant scientists to finally conceive the structure of the DNA molecule or to even conceive it as the hereditary material life. • In this opening genetics section it is important to understand scientists' achievements. • Appreciate and understand their method, do not get caught up in history and dates.

  6. The History of Molecular Genetics

  7. The early contributions: setting the stage • Gregor Mendel: mid 1800’s

  8. Gregor Mendel 1865 Gregor Mendel • By studying pea plants, • discover the basic rules of heredityof garden pea. • Characteristics are inherited in discrete units (later called genes) • An individual organism has two alternative heredity units for a given trait (dominant trait vs. recessive trait)

  9. Major events in the history between1800 - 1870 • 1869 Johann Friedrich Miescher discovered DNAand named it nuclein. 1881 Edward Zacharias showed chromosomesare composed of nuclein. Johann Miescher

  10. Major events in the history of Molecular genetics 1880 - 1900 • 1899 Richard Altmann renamed nuclein to nucleic acid. • By 1900, chemical structures of all 20 amino acidshad been identified • 1902 - Emil Hermann Fischer wins Nobel prize: showed amino acids are linked and form proteins Emil Fischer

  11. Major events in the history of Molecular Biology 1900-1911 • Thomas Hunt Morgan • Worked at Columbia University; later at CalTech • Studied fruit fly eye color, determining that trait was sex-linked • Won the Nobel Prize in 1933 for his work on chromosomes and genetics • 1911 – Thomas Hunt Morgan discovers genes on chromosomes are the discrete units of heredity Thomas Morgan

  12. The early contributions: setting the stage early 1900’s • Studied fruit fly eye color, determining that trait was sex-linked • 1911 – Thomas Hunt Morgan discovers genes on chromosomes are the discrete units of heredity • Won the Nobel Prize in 1933 for his work on chromosomes and genetics

  13. The early contributions: setting the stage • By this point, it was known that genetic material was located on a chromosome • This genetic material was in discrete units called genes

  14. All Life depends on 3 critical molecules Components Involve in Molecular Biology DNA RNA Protein By this stage , It was NOT known whether the gene was simply a protein, or whether it was composed of DNA

  15. A Brief History • Since the late 1950s and early 1960s, molecular biologists have learned to • Characterize, isolate, and manipulate the molecular components of cells and organisms, which are: • DNA, the storage of genetic information • RNA • Proteins, the major structural and enzymatic type of molecule in cells.

  16. Discovery of DNA • 1930’s • Various experiments identify chromosomes as the source of genetic information • Chromosomes are composed of mainly proteins and deoxyribonucleic acid (DNA) • The DNA molecule was considered too simple to be important so proteins were thought to carry the genetic information

  17. The Molecular Basis of Inheritance Evidence that DNA is a genetic material Came from

  18. Important Early Discoveries Fred Griffith (1928)– Experiments with pneumonia and bacterial transformation determined that there is a molecule that controls inheritance. Oswald T. Avery (1944)- Transformation experiment determined that DNA was the genetic material responsible for Griffith’s results (not RNA). Erwin Chargaff (1947)– noted that the the amount of A=T and G=C and an overall regularity in the amounts of A,T,C and G within species. Hershey-Chase Experiments (1952)– discovered that DNA from viruses can program bacteria to make new viruses.

  19. Frederick Griffith • Late 1920’s Frederick Griffith from Britain worked with bacteria “Streptococcus pneumoniae” • Defined the term, “TRANSFORMATION”

  20. In 1944, Oswald Avery, Maclyn McCarty, and Colin MacLeod announced that the transforming substance was DNA • Their conclusion was based on experimental evidence that only DNA worked in transforming harmless bacteria into pathogenic bacteria

  21. 1952, Hershey-Chase Bacteriophage Experiment Hershey and Chase concluded that the injected DNA of the phage provides the genetic information that makes the infected cells produce new viral DNA and proteins, which assemble into new viruses.

  22. Conclusions about these early experiments: Griffith 1928 & Avery 1944: DNA (not RNA) is transforming agent. Hershey-Chase 1953: DNA (not protein) is the genetic material. - RNA (not protein) is genetic material of some viruses, - but no known prokaryotes or eukaryotes use RNA as their genetic material. Alfred Hershey Nobel Prize in Physiology or Medicine 1969

  23. THE RACE IS ON!Who discovers the double helix?

  24. Linus Pauling • Won Nobel prize in chemistry in 1954 for work in chemical bonding; • Nobel peace prize in 1962 for his campaign against above-ground nuclear testing • He also worked on the structure of DNA, but came up with a TRIPLE HELIX • He thought DNA was 3 strands with the phosphates on the inside

  25. DNA Structure based on Two primary sources of information: • 1950 – Edwin Chargaff find • CytosinecomplementsGuanine • andAdeninecomplementsThymine • X-ray diffraction studies of Rosalind Franklin & Maurice H. F. Wilkins to study the structure of DNA. • The diffraction pattern can be used to deduce the three-dimensional shape of molecules. Edwin Chargaff What about? Rosalind Franklin

  26. Franklin and Wilkins • Their results using X-ray crystallography gave Watson and Crick the necessary information they needed to come up with the double helix structure • Width of the helix • Spacing of the nitrogenous bases • DNA molecule was made up of two strands, forming a double helix

  27. James Watson and Francis Crick 1953 proposed the Double Helix Model based on two sources of information

  28. Structure of DNA • Base composition studies of Erwin Chargaff • indicated double-stranded DNA consists of • ~50% purines (A,G) and ~50% pyrimidines (T, C) • amount of A = amount of Tand • amount of G = amount of C (Chargraff’s rules) • %GC content varies from organism to organism Examples: %A %T %G %C %GC Homo sapiens 31.0 31.5 19.1 18.4 37.5 Zeamays25.6 25.3 24.5 24.6 49.1 Drosophila 27.3 27.6 22.5 22.5 45.0 Aythyaamericana25.8 25.8 24.2 24.2 48.4

  29. Two sources of information Structure of DNA James D. Watson/Francis H. Crick 1953 proposed the Double Helix Model based on two sources of information: X-ray diffraction studies by Rosalind Franklin & Maurice Wilkins Conclusion-DNA is a helical structure with distinctive regularities, 0.34 nm & 3.4 nm.

  30. Watson, J.D. and F.H. Crick, “Molecular Structure of Nucleic Acids. Francis H.Crick James D.Watson 1962: Nobel Prize in Physiology and Medicine Conclusion-DNA is a helical structure with distinctive regularities, 0.34 nm & 3.4 nm.

  31. Major events in the history of Molecular Biology 1950 - 1952 • 1941 – George Beadle and Edward Tatum identify thatgenes make proteins • 1950s – Mahlon Bush Hoagland first to isolate tRNA • 1952 – Alfred Hershey and Martha Chase makegenes from DNA George Beadle Edward Tatum • 1956 George Emil Palade showed the site of enzymes manufacturing in the cytoplasm is made on RNA organelles called ribosomes. George Emil Palade Mahlon Hoagland

  32. Major events in the history of Molecular Biology 1970 • 1970 Howard Temin and David Baltimore independently isolate the first restriction enzyme • This means that: DNA can be cut into reproducible pieces at specific site by restriction enzymes called endonuclease • The pieces can be linked to bacterial vectors and introduced into bacterial hosts.This is called (gene cloning or recombinant DNA technology)

  33. Major events in the history of Molecular Biology 1970- 1977 • 1977 Phillip Sharp and Richard Roberts demonstrated that pre-mRNA is processedby the excision of introns and exonsare spliced together. Phillip Sharp Richard Roberts

  34. Major events in the history of Molecular Biology 1986 - 1995 • 1986 Leroy Hood: Developed automatedsequencing mechanism • 1986Human Genome Initiative announced • 1995 Moderate-resolution maps of chromosomes 3, 11, 12, and 22 were published • These maps provide the locations of “markers” on each chromosome to make locating genes easier Leroy Hood

  35. Major events in the history of Molecular Biology 1995-1996 • 1995 John Craig Venter: First bacterial genomes sequenced • 1995 Automated fluorescent sequencing instruments and robotic operations • 1996 First eukaryotic genome-yeast-sequenced John Craig Venter

  36. Major events in the history of Molecular Biology • Molecular Biology 1997-1999 • 1999First human chromosome (number 22) sequenced • Molecular Biology 2000-2001 • 2001 International Human Genome Sequencing published the first draft of the sequence of the human human genome

  37. Major events in the history of Molecular genrtics 2003- Present • April 2003 Human Genome Project Completed • Mouse genome is sequenced. • April 2004 Rat genome sequenced. • Next-generation sequencing – genomes being sequenced by the dozen

  38. Molecular genetics • Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. • Molecular genetics employs the methods of genetics and molecular biology to elucidate molecular function and interactions among genes. It is so called to differentiate it from other sub fields of genetics such as ecological genetics and population genetics. • Molecular genetics helps in understanding developmental biology, genetic mutations that can cause certain types of diseases. • Through utilizing the methods of genetics and molecular biology, molecular genetics discovers the reasons why traits are carried on and how and why some may mutate.

  39. Thank you

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