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CCR5-Δ32 deletion allele and sickle cell trait
22.09.15 Larissa von Buol & Salome Bechtler 1
Polymorphism and disease resistance
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§ Mechanism and distribution
§ Bubonic plague vs. smallpox
§ Model description
§ Dominant vs. incomplete dominace
§ Discussion
22.09.15 Larissa von Buol & Salome Bechtler 2
Agenda: CCR5-Δ32 deletion allele
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CCR5-receptor and HIV-1
Img. 1
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Distribution of the allele
Img. 2
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§ Ca. 1350-1750
§ Affects all ages
§ Episodic occurence with high death rates (15-40% of population)
§ Transmission by rodents
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Bubonic plague
Img. 3
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§ Until1978 § Affects mainly children
§ More continuous, 5 year peaks (30% case fatality)
§ Transmission between humans
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Smallpox
Img. 4
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§ 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)
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Modell description
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Dominance: plague
Img. 5
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Dominance: smallpox
Img. 6
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§ Heterozygotes have 50% protection
§ Plague: s = 0.09
§ Smallpox s = 0.17
§ Smallpox would need 1135 years
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Incomplete dominance
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§ Smallpox affects younger people (reproductive potential!)
§ Smallpox existed until 1978 (start of AIDS)
§ HIV and poxvirus: disease similarities
§ Geographical distribution
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Discussion
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Distribution of the allele
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§ Sickle-Cell anaemia § Malaria § Relation between Malaria and Sickle-cell Trait
§ Observation
§ Discussion
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Agenda: Sickle cell trait
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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
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Malaria
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• Mosquito-borne infectious disease
• Female Anopheles mosquito • Parasitic protozoans (Plasmodium)
à Fever, fatigue, vomiting, headaches
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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
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Relation between Malaria and Sickle-cell Trait
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Observation 1
Img. 9
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Observation 2
Img. 10
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§ 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
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Discussion
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§ 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.
§ https://en.wikipedia.org/wiki/HIV, 18.09.15 § https://en.wikipedia.org/wiki/Malaria, 20.09.2015 § https://en.wikipedia.org/wiki/Sickle-cell_disease, 20.09.2015
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Sources
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§ Img. 1:http://www.hindawi.com/journals/isrn/2013/728392/fig2/, 18.09.15 § Img. 2: Galvani, A. et al. (2005). The Geographic spread of the CCR5- Δ32 HIV resistance allele. PLOS.
§ Img. 3: http://yourstory.com/2014/07/bubonic-plague/, 19.09.15 § Img. 4: https://en.wikipedia.org/wiki/Smallpox, 19.09.15 § Img. 5 & 6: Galvani, A. & Slatkin, M. (2003). Evaluating plague and
smallpox as historical selective pressures for the CCR5- Δ32 HIV-resistance allele. PNAS.
§ Img. 7: https://en.wikipedia.org/wiki/Sickle-cell_disease ,19.09.2015 § Img. 8: http://rstb.royalsocietypublishing.org/content/366/1579/2806 ,
20.09.2015 § Img. 9,10: Allison, A. (1954). Protection afforded by sickle-cell trait
against subtertian malarial infection. The Basis of sensation.
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Sources: Images