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Unformatted text preview: IB35ac Class 18: Blood There is a lot of variation within the various characteristics of our blood, and much of this variation has been, and continues to be patterned by different environmental factors around the world. Today we will talk about the impacts of mosquitoes and diarrhea on human variation. 10/26/2009 IB35 Human Biological Variation Class #18 Topics for Today Founders & affected phenotypes Sickle cell anemia Blood types ABO Rh+ and Rh- Topics for today:
Blood & Disease How disease has affected the pattern of human variation Worldwide causes of death What is a founder?
Other diseases Digestive diseases Respiratory disease Injuries TB HIV Respiratory Infections Malaria Other infections Stroke A person who has a mutation that is then passed down through generations. Everyone with the mutation is related they have it in common because they are "identical by descent". Other Cancer Heart Disease Diabetes Hereditary hemochromatosis ->Over-abundance of iron in the body ->1 founder event Large percentage of causes of deaths due to diseases What is an affected phenotype?
->Some populations have higher frequencies of certain diseases due to founder mutations leading to trickle down effect ->Importance of geographic ancestry
Crossing Over ->Occurs during meiosis ->Gametes 1 10/26/2009 ->Reduction in the number or volume of RBCs ->Or when protein in RBC not functioning properly Sickle Cell Anemia Sickle Cell Anemia
Symptoms: -- abnormally shaped red blood cells -- local tissue death -- skin lesions infection -- episodes of excruciating pain -- greatly reduced lifespan classic example simple genetic disorder RED BLOOD CELLS ->Transport oxygen from lungs to all parts of the body ->Release oxygen at tissues and take up carbon dioxide Hemoglobin ->Protein in RBC that carries oxygen ->Helps in uptake of carbon dioxide Sickle Cell Anemia
abnormally shaped red blood cells What causes RBCs to sickle? Missense mutation = abnormal hemoglobin Change of 1 base pair What causes RBCs to sickle?
6th amino acid chain hemoglobin What causes RBCs to sickle? Glutamic Acid
hydrophilic Missense Mutation Valine
hydrophobic HbS hemoglobin crystallizes into long rods within RBCs when deoxygenated. HbA HbS 2 10/26/2009 How is sickle cell anemia inherited?
autosomal recessive HbA dominant HbS recessive HbA/HbA and HbA/HbS individuals have an essentially normal phenotype only HbS/HbS suffer sickle cell anemia ->Heterozygotes have sickle-cell traits (Carriers) ->Homozygous recessive have sickle cell disease In which populations is sickle cell anemia common? Sub-Saharan Africa North Africa N th Af i Arabia Southern Europe Central India ->Kids with sickle cell traits do not get malaria Infected female Anopheles mosquitoes spread the parasitic protozoa In which populations is sickle cell anemia common?
malarial environments What is malaria? Illness that causes spells of chills, fever and weakness Caused by 4 species of parasitic protozoa that infect human red blood cells Complex life cycle, need both a mosquito and a human host Genus: Plasmodium Species: falciparum, vivax, ovale, malariae (most serious)->(milder)
->Different variants of malaria for different animals ->MRCA 130mya 3 10/26/2009 Sickle Cell Anemia
An example of a balanced polymorphism
HbA/HbA dying of malaria HbA/HbS not dying of malaria or sickle cell HbS/HbS dying of sickle cell heterozygote advantage both homozygotes selected against, but for different reasons and to possibly different degrees MALARIA ->Episodic VS Chronic ->find out more, something to do with infecting animals instead of humans during certain periods Summary: Sickle Cell Anemia An autosomal recessive disease caused by a point mutation in the hemoglobin beta gene (HbB) found on chromosome 11. Carrier frequency of HbS varies significantly around the world, with high frequencies associated with zones of high malaria incidence. Evidence for Selection Carrier frequencies range from 5-40% across sub-Saharan Africa, the Middle East and parts of the Indian subcontinent. Higher frequencies in populations living in higher malarial-risk areas. ->Malaria accounts for 2-5% of all deaths ->Half the world's population at risk of contracting malaria ->Inherited autosomal co-dominant blood disease ->Underproduction of normal globin proteins ->May lead to formation of abnormal hemoglobin molecules causing anemia ->Decreased chance of contracting malaria How does this protect against malaria? The parasite inside the red cell produces acid. In the presence of acid, HbS has a tendency to polymerize which causes the cells to sickle. Since sickled cells are destroyed as the blood c cu a es oug circulates through the sp ee , the pa as es a e e spleen, e parasites are destroyed as well. Another thing that happens under low oxygen conditions is that potassium leaks out of HbScontaining cells. The parasite needs high potassium levels to develop. This may be the reason the parasite fails to thrive in red blood containing HbS. Is this the only genetic protection against malaria? Only homozygote has immunity Thalessemia HbC (parts of West and North Africa) HbE (eastern of Indian sub-continent) FY/Duffy gene ovalocytosis Only affected if person has Thalessemia as well Is sickle cell anemia an example of a founder event in human evolution? How would you test this hypothesis? ->By seeing if people share the base pairs around the allele for the HbS ->Crossing over moves huge chunks of DNA, so base pairs directly around the allele stay the same over many generations ->With sickle cell anemia, identified 6 founder events ->Oval or elliptical RBC ->Heterozygotes only ->Homozygotes inviable ->Immunity to P.falciparum ->Knocks out Duffy antigen on RBC ->P.vivax uses Duffy to enter RBC ->Restricted regions in West Africa ->Immunity for homozygotes 4 10/26/2009 Blood Groups A, B, AB, & O Rh+ and RhDuffy Others... ANTIGENS ->Situated on the cells ->Prompts generation of antibodies ANTIBODIES ->Float around in the bloodstream ->Used to neutralize foreign objects e.g. Bacteria and viruses Pictured here is a color-enhanced image of blood cells and platelets, magnified over 5,200 times by a scanning electron microscope. Fragments of precursor bone marrow cells that assist in blood clot formation Delivers oxygen to the body tissues Filled with hemoglobin hence red in color What is blood made up of?
Platelet Red blood cell Blood type is determined by a gene I that encodes a cell surface protein. The alleles are: IA, IB, and IO. A and B alleles produce a slightly different version of a gene product, and O produces no gene product. White blood cell Liquid component of blood Plasma Defend against infectious disease and foreign objects Blood Type Antigens Antibodies A A B B B A AB A+B None O None A+B The mutations... The gene makes galactosyl transferase A and B have 7 nucleotide differences 3 are silent
A allele O blood type (null) B allele O has just one nucleotide difference with A Deletion = frameshift mutation ->O Blood Type high frequency in the Americas ->A, B Blood Types high frequency in Europe and Asia 5 10/26/2009 What patterns the ABO blood groups? Drift or migration? Disease resistance? 1960s recognized a connection between blood groups and diarrhoea 1980s recognized that O blood type is much more susceptible to cholera infection Cholera Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period, from less than one day to five days, and produces an enterotoxin that causes a copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. Vomiting also occurs in most patients. ->Living in cities led to lower O blood type ->Better Hygiene standards ->Europe and Asia more dense so less O blood type ->Spread from contaminated food and water ->Hard to diagnose, because diarrhoea is a symptom of many other diseases What patterns the ABO blood groups? Drift or migration? Disease resistance? g 1960s recognized a connection between blood groups and diarrhoea 1980s recognized that O blood type is much more susceptible to cholera infection Resistance: AB, A, B, O Heterozygote advantage Some other things to think about Other examples of genetic resistance mice Genetic resistance to intestinal parasites in humans Conclusions The majority of genetic variation in disease resistance/susceptibility is clinal. Human migration Disease location & spread Host-parasite relationships have been and still been, are important in shaping the allele frequencies of many genes. Founder events can tell you about the nature of the disease and the selection pressure. Natural immunity = insights for developing vaccines and cures 6 ...
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This note was uploaded on 01/19/2011 for the course IB 35AC taught by Professor Hlusko during the Spring '08 term at Berkeley.
- Spring '08