Genetics Spring Final Review.docx

Cancer - caused by an uncontrolled division of abnormal cells in a part of the body a. Cancer is caused by an accumulation of detrimental variation in the genome over the course of a lifetime b. There are four main types i. Carcinoma: Arise in epithelial tissue that is found in the...

Cancer - caused by an uncontrolled division of abnormal cells in a part of the body a. Cancer is caused by an accumulation of detrimental variation in the genome over the course of a lifetime b. There are four main types i. Carcinoma: Arise in epithelial tissue that is found in the internal and external lining of the body. Adenocarcinomas develop in an organ or gland. Squamous cell carcinomas develop in the squamous epithelium of organs, including the skin, bladder, esophagus, and lung ii. Sarcoma: Arise from connective tissue that is found in bones, tendons, cartilage, muscle, and fat iii. Leukemia: Cancers of the blood that originate in bone marrow iv. Lymphoma: Cancers of the lymph system c. Types of Mutations: v. **Activating:** **c**auses the gene to be expressed at the wrong time, at the wrong level, or with a new function 1. *Activating* *mutations* *in* *[oncogenes]* *are* *tumorigenic.* vi. **Inactivating:** causes reduced function of a gene (less RNA or protein is made) 2. *Inactivating* *mutations* *in* [*tumor* *suppressors*] *are* *tumorigenic.* d. Somatic mutations are acquired by a *somatic* cell (all cells except eggs or sperm) that are passed on to daughter cells during cell proliferation. These mutations [cannot] be inherited by offspring. e. Germline mutations (aka inherited mutations) are present in a germ cell (egg or sperm) and are inherited by offspring -- genetic variation we are born with. vii. Women who inherit a BRCA1/2 mutation are at increased risk for breast cancer. viii. Individuals who inherit a CDH1 mutation are at increased risk for stomach cancer. f. Two Hit Hypothesis: Reminder: Humans have 2 copies of every gene ("diploid") -- one maternal, one paternal. Even if one copy (*allele*) of the gene is mutated, the other copy allows the protein to operate normally. ix. For a gene to be cancer-inducing, *both* copies of the gene must be affected. The second "hit" may alter the DNA (mutation) or alter the expression of the DNA (epigenetic). g. See slides on "Ten Cellular Hallmarks of Cancer Cells" 1. 1. 1. 2. 3. 4. 1. 1. b. 1. Normal human cells have a finite ability to undergo mitosis due to the ends of chromosomes (telomeres) shortening after each mitotic division 1. Once normal human cells reach the Hayflick's limit (generally 40-60 mitotic divisions), cells can go into G0 phase of cell cycle 1. Cancer cells are very different---they can greatly exceed "Hayflick's limit" and continue to undergo mitosis 1. Cancer cells are able to do this because they can elongate their telomeres using an enzyme called **[telomerase]** 1. c. 1. 1. These mutations are found in the oncogene and tumor suppressor genes discussed in Section 2 above d. 1. 1. However, due to Hallmark 2, most cancer cells avoid normal growth suppressor signals in the G1 checkpoint in order to continue proliferating 1. A Tumor Suppressor Gene, **p53,** functions as a central regulator of cell death because it stops the cell cycle upon detection of DNA damage e. 1. Normal cells can initiate apoptosis in response to abundant DNA damage and other cellular stresses 1. f. 1. Cancer cells have the ability to proliferate due to the aforementioned Hallmarks 1--4 as well as to over-active oncogenes  1. g. 1. Normal cells break glucose down (glycolysis) to pyruvate which provides energy adenosine triphosphate (ATP) for the cell 1. 1. This allows the cancer cell to divert metabolites for useful processes such as mitosis h. 1. The ever-alert immune system surveils the human body to destroy viruses, pathogens, and other foreign cell types, including tumor cells 1. Cells of the immune system that engulf and destroy foreign particles are B cells (secrete antibodies and cytokines), T lymphocytes, macrophages, and natural killer cells 1. **Cancer cells** can protect themselves by inhibiting T cells that would normally attack these cancer cells by having the **PDL-1** (Programmed Death Ligand -1) or **PDL-2** antigen which deflects the immune response i. 1. The presence of a tumor stimulates an inflammatory signal which brings red blood cells to the tumor site 1. j. 1. 1. 1. 1. 1. 1.  These new blood vessels provide a way for tumor cells to get into the bloodstream k. 1. ii. ii. ii. 1. 2. **Metastasis** 1. Definition - The process by which tumor cells move from the primary tumor to a different organ via lymph and/or blood (e.g.; prostate cancer cells metastasize to bone) 1. Terms to know 1. *Metastasize,* verb:  the act of moving from primary tumor to secondary organ 1. *Metastatic,* adjective: the state of being able to metastasize 1. *Metastases,* noun:  multiple metastatic tumors 1. **Benign** tumors are masses of cells that are unable to invade neighboring tissue or metastasize 1. **Malignant** tumors are cancerous masses of tumor cells that are able to invade neighboring tissue and metastasize 1. All tumors are capable of metastasizing 1. Dangers of metastasis: 1. 1. 1. 1. 1. 1. Including treatments for pain 1. 1. g. 1. **Primary tumor growth** - Cells grow uncontrollably until they become a mass; **[some never become metastatic and remain benign]** ii. iii. ** ** iv. v. vi. vii. 1. As depicted in the chart, the most common secondary sites for cancer are in the lung and liver 2. Evolution - change in populations over time A. The scientific theory that all living organisms on Earth descended from a common ancestor. 1. The structures and functions of all living organisms are encoded in the same basic nucleic molecules, DNA and RNA. B. Principles of Darwinian Evolution 2. Variation 3. Heritability 4. Overproduction 5. Reproductive Advantage C. Organisms that are best matched to their environment are more likely to survive and reproduce D. Adaptation -- a trait that improves an organism's change for survival and reproduction E. Natural Selection - Organisms with traits that help them survive and reproduce pass their characteristics to their offspring. 6. Helpful traits survive and spread through the population 7. Harmful traits disappear over time 8. As a result, a population may evolve into a new species F. Important to remember: Variation exists among individuals within a population 9. An individual with variations that make them poorly adapted to the environment will not survive and reproduce 10. Remember genotypes (genes) and phenotypes (expression of genes) 11. Evolution occurs as a population's genes and their frequencies change over time G. Extinction is a natural and important part of evolution 12. It is estimated that 999 of every 1,000 species that have ever lived on Earth have become extinct 13. The average species survives between 2 and 10 million years 14. Even the most highly adapted species become extinct. H. Two Main theories of Evolution: 15. Gradualism -- the idea that species originate through a gradual change of adaptations 16. Punctuated Equilibrium -- hypothesis that speciation occurs relatively quickly, in rapid bursts, with long periods of genetic equilibrium in between 1. Environmental changes, or introduction of competitive species can lead to rapid changes 2. Happens quickly -- in about 10,000 years or less 17. [Both gradualism and punctuated equilibrium are supported by fossil evidence] 3. Genetic Engineering - Changing the DNA in living organisms to create something. These organisms are called **[Genetically Modified Organism (GMO)]** I. Artificial selection - : breeders choose which organism to mate to produce offspring with desired traits. They cannot control what genes are passed. When they get offspring with the desired traits, the maintain them. A. selective breeding - when animals with desired characteristics are mated to produce offspring with those desired traits. Passing of important genes to next generation. (e.g., Champion race horses, cows with tender meat, large juicy oranges on a tree.) B. hybridization - two individuals with unlike characteristics are crossed to produce the best in both organisms. Example: Luther Burbank created a disease resistant potato called the Burbank potato. He crossed a disease resistant plant with one that had a large food producing capacity. Result: disease resistant plant that makes a lot of potatoes. C. inbreeding - breeding of organism that genetically similar to maintain desired traits. Dogs breeds are kept pure this way. It keeps each breed unique from others. Risk: since both have the same genes, the chance that a baby will get a recessive genetic disorder is high. J. **2.** Cloning - creating an organism that is an exact genetic copy of another. Identical twins are naturally created clones. 18. Clone: group of cells or organisms that are genetically identical as a result of asexual reproduction. They will have the same exact DNA as the parent. Image Detail K. Gene splicing - DNA is cut out of one organism and put into another organism. A trait will be transferred from one organism to another. For example: the human insulin gene can be removed from a human cell. It can be put into a bacterial cell. The bacterial will now make human insulin. **Gene therapy**: when disease causing genes are cut out and good gene are inserted. 4\. Gel electrophoresis: analyzing DNA. a technique used to compare DNA from two or more organisms. Why compare DNA: 1. Find genetic relatives 2. Who committed a crime. 3. How closely species are related.