Genetics Lecture Notes PDF

Genetics DNA Mutation LECTURE (11) DR. El-Sawy 0  Genetics DNA Mutation  When num...

Genetics DNA Mutation LECTURE (11) DR. El-Sawy 0  Genetics DNA Mutation  When number of bases removed from DNA.  Resulting in protein with fewer amino acids than normal. Deletion  Occurs when a portion of a chromosome is repeated. Duplication  Orientation of DNA segment reverses. Inversions  Large DNA segment moves to new location.  It is very common in some cancers  diagnosis of disease.  Example: exchange ( ) chromosomes 9 and 22 in 90% of patients with chronic myelogenous leukemia (CML). Translocations DR. El-Sawy 1  Genetics DNA Mutation  Instead of making single copy of a region of a chromosome, many copies are produced  production of many copies of genes located on that region of chromosome.  The genes on each of copies  transcribed and translated  overproduction of mRNA & protein corresponding to the amplified genes. Clinical significance 1. Gene amplification occurs quite often in cancer cells : If oncogene is included in amplified region  overexpression of that gene  deregulated cell growth. Gene Examples: myc oncogene in a wide range of tumors. Amplification 2. Contribute to one of the biggest problems in cancer TTT  Drug resistance Drug resistant tumors can continue to grow & spread even in presence of chemotherapy drugs. Gene commonly involved  MDR (multiple drug resistance). The protein product of this gene acts as a pump located in membrane of cells. It is capable of selectively ejecting molecules from cell, including chemotherapy drugs. This removal renders the drugs ineffective. DR. El-Sawy 2  Genetics DNA Mutation  Genes that protect against cancer.  They normally limit how much a cell can grow by: 1. Controlling how fast cells divide. Definition 2. Fixing mistakes in DNA. 3. Controlling when a cell dies.  Variants in tumor suppressor gene  allow cells to grow out of control  eventually form a tumor. 1. Mutation in BRCA1, BRCA2 gene: Increase risk of hereditary Breast, Ovarian, Pancreatic, and Prostate cancer. Increase risk of melanoma. 2. p53 or TP53 gene: Examples The most common tumor suppressor gene that mutates in people with cancer. This gene is missing or damaged in ˃ 1/2 of all cancers. ↑ risk of many different types of cancer. Inherited p53 mutations are rare. DR. El-Sawy 3  Genetics DNA Mutation  Mutated gene that has the potential to cause cancer.  Before oncogene becomes mutated, it is called proto-oncogene  play a role in regulating normal cell division. Definition  HER2: This gene makes a protein that controls cancer growth. Found in some cancer cells, as breast & ovarian cancer. If a breast cancer is "HER2 negative  HER2 gene is not making Examples this needed protein.  The RAS family of genes: These genes make proteins that help cells communicate with each other, grow normally, and die when they are supposed to. Mutations in these genes can turn healthy cells into cancer cells. DR. El-Sawy 4  Genetics DNA Mutation Definition:  The study of the molecular basis of benign (anemia) & malignant (leukemia) hematological disorders. Example:  Benign disorders as hemoglobinopathies :  Group of disease related to abnormal hemoglobin synthesis. Def  The best example for point mutation. 1. Sickle cell Disease (SCD) Examples 2. Beta thalassemia. 3. Alpha thalassemia. DR. El-Sawy 5  Genetics DNA Mutation β-Thalassemia Alpha Thalassemia Sickle Cell Disease (SCD) (Cooley’s, Mediterranean Anemia) (α thalassemia) Inheritance Autosomal recessive (AR). Type of  Missense point mutation.  More than 200 different gene mutations.  Large (exon or gene) deletion mutation. mutation  Mutation in codon 6 of beta globin gene (GAG→ GTG) → This change 6th amino acid in beta- chains of HB from glutamic  Mutation in α1-globin gene on Causes  Mutations on chromosome 11. acid to valine. chromosome 16.  This leads to polymerization of Hb & distortion of RBCs into a sickle shape.  Reduced synthesis of hemoglobin beta chain  Decreased alpha-globin production → that results in : excess of β chains in adults. a. ↓↓ amount of hemoglobin A (HbA)  The excess β chains form unstable  Chronic hemolytic anemia. Characterized b. ↑↑ amount of HB A2 and HB F. tetramers (called Hemoglobin H or  Presence of abnormal insoluble by c. microcytic hypochromic anemia HbH of 4 beta chains) which have hemoglobin S (Hb S).  It include all types of mutation. abnormal oxygen dissociation curves.  One patient may have one or more of these mutations. DR. El-Sawy 6  Genetics DNA Mutation  RBCs that are sickle shaped  lack flexibility  vaso Pathogenesis occlusive crisis  muscle pain and injury to tissues.  Fever.  Fatigue from anemia. Symptoms  Swelling of hands and feet.  Stroke.  Organ failure.  Blood transfusions which aid with ↑ number of normal RBCs Treatment  Bone marrow transplantation  produce healthy RBCs DR. El-Sawy 7