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GENETICS

GENETICS. GENETICS. Cells divide and pass on instructions coded in DNA of chromosomes Each chromosome is a huge DNA molecule with coded information DNA replicates to pass on information DNA is transcribed to make proteins that run cell metabolism

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GENETICS

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  1. GENETICS

  2. GENETICS • Cells divide and pass on instructions coded in DNA of chromosomes • Each chromosome is a huge DNA molecule with coded information • DNA replicates to pass on information • DNA is transcribed to make proteins that run cell metabolism • Cancer—example of what happens when genetic control goes awry • Normal inheritance and meiosis

  3. GENETICS • Cells divide and pass on instructions coded in DNA of chromosomes • Each chromosome is a huge DNA molecule with coded information • DNA replicates to pass on information • DNA is transcribed to make proteins that run cell metabolism • Cancer—example of what happens when genetic control goes awry • Normal inheritance and meiosis

  4. DNA and chromosomes • Long DNA molecules (millions of base pairs long) in nucleus are called chromosomes • Each chromosome is organized and packaged or wrapped up with proteins giving it a certain shape • In humans, 23 pairs of chromosomes • 1 of each pair from mother • 1 of each pair from father • Total view of all 23 pairs is called karyotype

  5. Mitosis—cell division • Why do cells divide? • Growth—so tissues/structures can become larger • Replacement—many tissues are constantly being replaced because they get worn out or used up. E.g. blood, skin, lining of gut, sperm • Repair—when tissues get damaged due to injury

  6. Mitosis—what happens (overview) • DNA/chrosomes replicate (make exact copies • Copies line up at center of cell • Copies pulled to opposite ends of cells by centromeres/spindles • Cell membrane pinches off and splits cell into two

  7. Mitosis—details/stages 1. Prophase 3. Anaphase 4. Telophase 2. Metaphase

  8. Chromosomes condense and become visible Nuclear envelope fragments Nucleolus disappears Centrosomes move to opposite poles Spindle fibers appear and attach to the centromere 1. Mitosis: Prophase

  9. Chromosomes line up at the middle of the cell (equator) Fully formed spindle 2. Mitosis: Metaphase

  10. Sister chromatids separate at the centromeres and move towards the poles 3. Mitosis: Anaphase

  11. Chromosomes arrive at the poles Chromosomes become indistinct chromatin again Nucleoli reappear Spindle disappears Nuclear envelope reassembles Two daughter cells are formed by a ring of actin filaments (cleavage furrow) 4. Mitosis:Telophase and cytokinesis

  12. Mitosis—constant, fast, keeps body functioning • Remember, mitosis produces two identical daughter cells • Mitosis is constantly happening in your body to allow for growth, replacement and repair • While you read this slide, millions of new cells were produced by mitosis in the tissues of your body! • Don’t forget cellular scale and intelligence—it’s a whole planet happening at the sub-microscopic level

  13. GENETICS • Cells divide and pass on instructions coded in DNA of chromosomes • Each chromosome is a huge DNA molecule with coded information • DNA replicates to pass on information • DNA is transcribed to make proteins that run cell metabolism • Cancer—example of what happens when genetic control goes awry • Normal inheritance and meiosis

  14. Chrosomes • REVIEW: Each chromosome is a single DNA molecule wrapped up within a special group of proteins giving it a particular shape

  15. DNA is structured to replicate • DNA is “double helix”—two complementary strands wound in a spiral • Strands separate and DNA replicates by filling in other half of each separated strand • Famous Watson-Crick model (Nobel prize)

  16. DNA replicates to pass on information (to daughter cells in mitosis)

  17. DNA is transcribed to make proteins that run cell metabolism • DNA is transcribed to mRNA • mRNA is translated to amino acid sequence • Amino acid sequence folds up into protein • Proteins catalyze reactions of cell metabolism • This process is called “gene expression”—the information in one region of the DNA—a “gene”—is being expressed so that the cell’s metabolism can function

  18. 2 steps of gene expression • Transcription – DNA is read to make a mRNA in the nucleus of our cells • Translation – Reading the mRNA to make a protein in the cytoplasm

  19. Transcription • Happens in nucleus • DNA double helix “opens up” • mRNA transcript is made from DNA template

  20. Translation • Happens outside nucleus • Ribosomes (special RNA particles or organelles) do the translation • They glom onto mRNA and line up amino acids according to mRNA sequence (see next slide for “code”

  21. RNA-protein translation code • Every three RNA bases codes for one amino acid • This code is very evolutionary conservative—works almost the same in all forms of life

  22. Overview of transcription and translation REMEMBER: A particular region of DNA that has the code to make a particular protein is called a “gene.” Details in web link video animations

  23. How does cell decide when to activate which genes to produce what proteins? • DNA must be unpackaged and uncoiled in order to be transcribed to mRNA • Lampbrush chromosome shows loops of DNA that are being transcribed • What determines which regions or genes are going to be transcribed and translated? • This is called regulation of gene expression

  24. Regulation of gene expression • Gene expression is regulated—not all genes are constantly active and having their protein produced • The regulation or feedback on gene expression is how the cell’s metabolism is controlled. • This regulation can happen in different ways: • 1. Transcriptional control (in nucleus): • e.g. chromatin density and transcription factors • 2. Posttranscriptional control (nucleus) • e.g. mRNA processing • 3. Translational control (cytoplasm) • e.g. Differential ability of mRNA to bind ribosomes • 4. Posttranslational control (cytoplasm) • e.g. changes to the protein to make it functional • When regulation of gene expression goes wrong—cancer!

  25. DNA technology • Recombinant DNA • DNA sequencing and Human Genome Project • “Genetic Engineering” NOTE: This is probably going to be the century for biological technology. What we’ve done with smart silicon systems will soon seem like nothing compared to what we will do with smart carbon/life-based systems. The technologies to understand, build, manipulate and control DNA, protein and cellular systems have been growing for the last fifty years and will undoubtedly keep doing so. Please view the web links and do the ethical issue essay for this part of the course. I think you’ll find the DNA technologies and our ability to manipulate cell metabolism fascinating!

  26. GENETICS • Cells divide and pass on instructions coded in DNA of chromosomes • Each chromosome is a huge DNA molecule with coded information • DNA replicates to pass on information • DNA is transcribed to make proteins that run cell metabolism • Cancer—example of what happens when genetic control goes awry • Normal inheritance and meiosis

  27. Characteristics of cancer cells • Lack differentiation and do not contribute to body functioning • Have abnormal nuclei that are enlarged and may have an abnormal number of chromosomes • Unlimited ability to divide • one way is through turning on the telomerase gene that allows telomeres on chromosomes to continually be built thus allowing a cell to divide over and over again • Form tumors • Benign tumors are usually encapsulated and do not invade adjacent tissue while a cancerous tumor usually is not encapsulated and eventually invades surrounding tissue • Can divide without growth factors • Become abnormal gradually through a multistage process • Undergo angiogenesis and metastasis

  28. The 3 phases in the development of cancer cells • Initiation – a single cell undergoes a mutation that causes it to divide repeatedly • Promotion – a tumor develops and cells within the tumor mutate • Progression – a cell mutates in such a way that allows it to invade surrounding tissue

  29. The genetic basis for cancer • Proto-oncogenes – products promote the cell cycle and prevent cell death (apoptosis) • Tumor-suppressor genes – products inhibit the cell cycle and promote apoptosis • Mutations in the genes above can cause cancer, in fact proto-oncogenes that have mutated are cancer-causing genes called oncogenes

  30. Comparing these genes in normal and cancer cells

  31. Types of cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Oncology – study of cancer • Carcinomas: cancers of the epithelial tissue • Adenocarcinomas: cancers of glandular epithelial cells • Sarcomas: cancers of muscle and connective tissues • Leukemias: cancers of the blood • Lymphoma: cancers of lymphatic tissues

  32. Causes of cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Genetics • Environmental carcinogens • Radiation • Environmental carcinogens (tobacco smoke and pollutants) • Viruses

  33. Genetic causes of cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Examples of genes associated with cancer: • BRCA1 and BRCA2 – tumor-suppressor genes that are associated with breast cancer • RB – a tumor-suppressor gene that is associated with an eye tumor • RET – proto-oncogene that is associated with thyroid cancer • Mutations of these genes predispose individuals to certain cancers but it takes at least one more acquired mutation during their lifetime to develop cancer

  34. Environmental causes of cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Radiation: • Environmental factors such as UV light (in sunlight or tanning lights) and x-rays can cause mutation in DNA • Organic chemicals: • Tobacco smoke: increases cancer of lungs, mouth, larynx and others • Pollutants: substances such as metals, dust, chemicals and pesticides increase the risk of cancer • Viruses: • Hepatitis B & C: virus that can cause liver cancer • Epstein-Barr virus: can cause Burkitt’s lymphoma • Human papillomavirus: can cause cervical cancer

  35. Seven warning signs of cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Change in bowel or bladder habits • A sore that does not heal • Unusual bleeding or discharge • Thickening or lump in breast or elsewhere • Indigestion or difficulty in swallowing • Obvious change in wart or mole • Nagging cough or hoarseness

  36. Self-examination – monthly exams of breasts and testicles starting at age 20 Colonoscopy – every 5 years starting at age 50 Mammogram – yearly after age 40 Pap smear – should begin these 3 years after vaginal intercourse or no later than age 21 Some routine screening tests for cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?

  37. Health Focus: Self exams CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?

  38. A – asymmetry B – border is irregular C – color varies from one area to another D – diameter is larger than 6mm Detecting skin cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?

  39. Other ways to detect cancer CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Tumor marker tests – blood tests for tumor antigens/antibodies • CEA (carcinoembryonic antigen) antigen can be detected in someone with colon cancer • PSA (prostate-specific antigen) test for prostate cancer • Genetic tests – tests for mutations in proto-oncogenes and tumor-suppressor genes • RET gene (thyroid cancer) • P16 gene (associated with melanoma) • BRCA1 (breast cancer) • A diagnosis of cancer can be confirmed by performing a biopsy

  40. Standard cancer treatments CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Surgery – removal of small cancers • Radiation therapy – localized therapy that causes chromosomal breakage and disrupts the cell cycle • Chemotherapy – drugs that treat the whole body that kills cells by damaging their DNA or interfering with DNA synthesis • Bone marrow transplants – transplant bone marrow from one individual to another

  41. Newer cancer therapies CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Immunotherapy – inject immune cells that are genetically engineered to bear the tumor’s antigens • Passive immunotherapy – antibodies that are linked to radioactive isotopes or chemotherapeutic drugs are injected into the body • p53 gene therapy – a retrovirus in clinical trial that is injected into the body where it will infect and kill only tumor cells (cells that lack p53 = tumor cells) • Angiogenesis inhibition - Angiostatin and endostatin are drugs in clinical trials that appear to inhibit angiogenesis

  42. Bioethical focus: Control of tobacco CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT? • Food for thought: • Smoking diminishes the health of the smoker and damages nearly every major organ • Within minutes of smoking, a smoker’s body begins to heal • Smoking low-tar or low-nicotine is no different than smoking any other cigarette • The tobacco industry targets young people (9 out of 10 smokers start before age 18) • It is the single most preventable cause of death and disease in the US • Give your thoughts: • Who should pay for the medical bills associated with smoking? • Should the government prevent the sale of tobacco or leave it up to the individual?

  43. GENETICS • Cells divide and pass on instructions coded in DNA of chromosomes • Each chromosome is a huge DNA molecule with coded information • DNA replicates to pass on information • DNA is transcribed to make proteins that run cell metabolism • Cancer—example of what happens when genetic control goes awry • Normal inheritance and meiosis

  44. How are genetic traits combined and passed on from parent to offspring • Meiosis produces gametes or sex cells (eggs and sperm) with just one member of each chromosome pair • Fertilization results in union of female gamete (egg) with male gamete (sperm) • Subsequent embryonic, fetal and embryonic development by mitosis and differentiation of cell types produces new individual

  45. 18.3 Meiosis Overview of meiosis • Two nuclear divisions occur to make 4 haploid cells (cells with just one member of each chromosome pair) • Meiosis results in gametes (egg and sperm) • Has 8 phases (4 in each meiosis I & II)

  46. Alleles • A particular gene, or protein-coding region of DNA along a chromosome might have a few different variations, called alleles • The combination of alleles, at a particular gene, or chromosome region, that you get from your mother and father determine your hereditary traits • Please see the Dragon Genetics lab to understand this (in online lab links for this section)

  47. Fertilization • After meiosis, male and female gametes (sperm and egg) unite to form a new cell—a zygote—that has the full set of 23 pairs of chromosomes.

  48. Embryonic development—mitosis produces tissues/structures of adult

  49. Some adult features are coded for genetically in alleles or gene varieties of sperm and egg Be sure to see sickle cell anemia example in Web Links for this section of the course

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