Polymorphism and disease resistance
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1 Polymorphism and disease resistance CCR5-Δ32 deletion allele and sickle cell trait Larissa von Buol & Salome Bechtler
2 Agenda: CCR5-Δ32 deletion allele Mechanism and distribution Bubonic plague vs. smallpox Model description Dominant vs. incomplete dominace Discussion Larissa von Buol & Salome Bechtler
3 CCR5-receptor and HIV-1 Img. 1 Larissa von Buol & Salome Bechtler
4 Distribution of the allele Img. 2 Larissa von Buol & Salome Bechtler
5 Bubonic plague Ca Affects all ages Episodic occurence with high death rates (15-40% of population) Img. 3 Transmission by rodents Larissa von Buol & Salome Bechtler
6 Smallpox Until1978 Affects mainly children More continuous, 5 year peaks (30% case fatality) Transmission between humans Img. 4 Larissa von Buol & Salome Bechtler
7 Modell description Temporal disease patterns Age specific nature of disease Plague: upper mortality estimates Smallpox: 30% case fatality Erradication: Plague: 1750 Smallpox: 1978 s = the average selection coefficient per generation acting on the resistance allele Time period: 700 years (28 generations) Larissa von Buol & Salome Bechtler
8 Dominance: plague Img. 5 Larissa von Buol & Salome Bechtler
9 Dominance: smallpox Img. 6 Larissa von Buol & Salome Bechtler
10 Incomplete dominance Heterozygotes have 50% protection Plague: s = 0.09 Smallpox s = 0.17 Smallpox would need 1135 years Larissa von Buol & Salome Bechtler
11 Discussion Smallpox affects younger people (reproductive potential!) Smallpox existed until 1978 (start of AIDS) HIV and poxvirus: disease similarities Geographical distribution Larissa von Buol & Salome Bechtler
12 Distribution of the allele Larissa von Buol & Salome Bechtler
13 Agenda: Sickle cell trait Sickle-Cell anaemia Malaria Relation between Malaria and Sickle-cell Trait Observation Discussion Larissa von Buol & Salome Bechtler
14 Sickle-Cell anemia Hereditary blood disorder Abnormality in the oxygen-carrying haemoglobin molecule in RBCs Abnormal, sickle-like shape à Various acute and chronic complications Img. 7 Larissa von Buol & Salome Bechtler
15 Malaria Mosquito-borne infectious disease Female Anopheles mosquito Parasitic protozoans (Plasmodium) à Fever, fatigue, vomiting, headaches Img. 8 Larissa von Buol & Salome Bechtler
16 Relation between Malaria and Sickle-cell Trait Beet (1946) 102 sicklers à 10 (9,8%) showing malaria parasites 491 non-sicklers à 75 (15,3%) showing malaria parasites à Statistically highly significant Larissa von Buol & Salome Bechtler
17 Observation 1 Img. 9 Larissa von Buol & Salome Bechtler
18 Observation 2 Img. 10 Larissa von Buol & Salome Bechtler
19 Discussion Individuals with the Sickle-cell trait suffer from malaria less often and less severely than those without the trait Polymorphism: heterozygote has an advantage over either homozygote Larissa von Buol & Salome Bechtler
20 Sources Allison, A. (1954). Protection afforded by sickle-cell trait against subtertian malarial infection. The Basis of sensation. Franklin Bunn, H. (2015). The triumph of good over evil: protection by the sickle gene against malaria. Perspectives. Galvani, A. & Slatkin, M. (2003). Evaluating plague and smallpox as historical selective pressures for the CCR5- Δ32 HIV-resistance allele. PNAS Larissa von Buol & Salome Bechtler
21 Sources: Images Img. 1: Img. 2: Galvani, A. et al. (2005). The Geographic spread of the CCR5- Δ32 HIV resistance allele. PLOS. Img. 3: Img. 4: Img. 5 & 6: Galvani, A. & Slatkin, M. (2003). Evaluating plague and smallpox as historical selective pressures for the CCR5- Δ32 HIVresistance allele. PNAS. Img. 7: Img. 8: Img. 9,10: Allison, A. (1954). Protection afforded by sickle-cell trait against subtertian malarial infection. The Basis of sensation. Larissa von Buol & Salome Bechtler
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