Hlth 103 - Biological Determinants of Health - Genes & Genetics - PDF

HLTH 103 – Biological Determinants of Health Genes & Genetics Health Sciences PART A Genes & Genetics  PART A:  Case Study: Sickle Cell Anemia & Malaria  Part B:  Gregor Mendel & Mendelian Genetics  Patterns of Inheritance Beyond Mendel  Part C:  Genes, Genetics, and Ge...

HLTH 103 – Biological Determinants of Health Genes & Genetics Health Sciences PART A Genes & Genetics  PART A:  Case Study: Sickle Cell Anemia & Malaria  Part B:  Gregor Mendel & Mendelian Genetics  Patterns of Inheritance Beyond Mendel  Part C:  Genes, Genetics, and Genomics  Nucleic Acids (Cellular Building Blocks)  Processing of Genetic Content Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Malaria & Sickle Cell Anemia Case Study: Malaria & Sickle Cell Anemia  What is Malaria?  What is sickle cell disease?  What are the physiological consequences of sickle cell disease?  What is the inheritance pattern of sickle cell disease?  What is the molecular sequence of hemoglobin? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  Tony Allison grew up in Kenya and became interested in human evolution and eventually malaria, which he contracted at age 10  Malaria is a disease caused by a parasite carried by the Anopheles mosquito and can be fatal Source: BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2243 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  Malaria is a serious infection with serious health consequences in the human population  transmitted by: mosquito of the genus Anopheles  caused by: Protozoan of genus Plasmodium  most common genus and species: Plasmodium falciparum  single celled  eukaryotic organism  no flagella  penetrates human RBC (red blood cells)  destroys human RBCs  can infect other human cells Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Infected Red blood Penetration of Red blood Cells Cells Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  malaria infection can involve general malaise, fatigue, vague aches, and nausea  some people may experience chills, fever, and sweating  treatment will involve efforts to alleviate pain and discomfort  a combination of antimalarial drugs will also be used  prevention will involve a variety of efforts …  in-class Q&A: what are at least 4-preventative efforts? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  Dr. Allison, after receiving his medical degree in England, returned to Kenya in 1949  Collected blood samples from various tribes and tested them for red blood cell membrane proteins to see whether there may be a genetic relationship  Also tested for the presence of sickle cells, an abnormal type of red blood cell  The presence of sickle cells indicates sickle cell disease, an inherited disorder where red blood cells appear sickle shaped  No pattern emerged when looking at the red blood cell membrane proteins  However, more than 20% of individuals living near water had the sickle cell trait Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  Sickle cell disease is a severe inherited genetic disorder.  In sickle cell disease, red blood cells that are normally disc shaped and flexible become rigid and pointy shaped.  Sickled cells get stuck in blood vessels, which can lead to blood clots and other serious physical consequences, including kidney failure, paralysis, and heart failure.  The inheritance of the gene associated with sickle cell disease also confers resistance against malaria. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Global Distribution of Malaria Source: CDC Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria  Dr. Allison was interested in whether there was a relationship between the possession of the sickle cell trait and resistance to malaria  He designed three studies to test this hypothesis  All three studies led to the conclusion that the possession of the sickle cell trait afforded some protection against malaria  Dr. Allison discovered a connection between malaria & sickle cell anemia in the 3-studies shown in the figure  He discovered that the inheritance of the gene associated with sickle cell disease also confers resistance or protection against malaria infection! Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Study #1 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Study #2 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Study #3 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Study #3 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Sick Cell Disease  Dr. James Herrick examined some blood taken from a person with anemia, a disease in which a person is deficient in hemoglobin (the protein that carries oxygen in the blood)  He noticed that the red blood cells were sickle-shaped  Later, it was discovered that the red blood cells would become sickle- shaped under a low-oxygen condition  Sickle cell disease is the most common inherited blood disorder in the United States  Normal red blood cells are flexible, but sickle cells are rigid and can get stuck, forming blood clots Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Sick Cell Disease  In sickle cell anemia red blood cells become abnormally shaped and rigid  sickle shaped or shaped like a comma  sickled cells get stuck in blood vessels, which can lead to blood clots and other serious physical consequences, including kidney failure, paralysis, and heart failure.  sickle cell disease is a severe inherited genetic disorder of red blood cells.  HbA: normal hemoglobin  HbS: abnormal hemoglobin Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Sick Cell Disease Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Pathophysiology Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Sick Cell Disease – Molecular Structure of Hemoglobin  Dr. James Herrick examined some blood taken from a person with anemia, a disease in which a person is deficient in hemoglobin (the protein that carries oxygen in the blood)  Once HbA gives up oxygen it goes back to its normal shape.  Once HbS gives up oxygen it forms long fibers. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Inheritance Pattern  Inheriting one copy of HbA and one copy of HbS means that the person will be a carrier of the disorder  Inheriting one copy of HbA and one copy of HbS means that the person will be a carrier of the disorder  to get sickle cell disease, the person has to inherit one copy of HbS from the mother, and one copy of HbS from the father as shown in the pedigree analysis in the figure Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Molecular Structure of Hemoglobin Could Molecular Medicine Prevent Sickle Cell Disease?  Linus Pauling became interested in using sickle cell disease. He wanted to see if the disease could be studied, prevented or cured at the biochemical level  Began by studying HbA and HbS to see if they were chemically different Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Molecular Structure of Hemoglobin Could Molecular Medicine Prevent Sickle Cell Disease?  He discovered that they had a different distribution and localization of electrical charges on their surfaces  He also demonstrated that carriers contained an equal mix of HbA and HbS  He was able to show that one could trace the cause of a disease to an alteration in the structure of a protein  Pauling argued that because sickle cell disease was inherited, genes must determine the structure of proteins  Ushered in the age of molecular medicine and how it aims to understand the way genes, proteins, and other molecules work in order to diagnose and treat disease Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Molecular Structure of Hemoglobin Could Molecular Medicine Prevent Sickle Cell Disease?  It wasn’t until much later that the exact difference between HbA and HbS was discovered  Vernon Ingram was able to show that they differ in just one amino acid (the building blocks of proteins) Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Sick Cell Disease – Molecular Structure of Hemoglobin Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Case Study Connection Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Case Study: Sickle Cell Disease & Malaria Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press