Polymorphism and disease resistance
CCR5-Δ32 deletion allele and sickle cell trait
Larissa von Buol & Salome Bechtler |
22.09.15
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Agenda: CCR5-Δ32 deletion allele
§  Mechanism and distribution
§  Bubonic plague vs. smallpox
§  Model description
§  Dominant vs. incomplete dominace
§  Discussion
Larissa von Buol & Salome Bechtler |
22.09.15
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CCR5-receptor and HIV-1
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Distribution of the allele
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Bubonic plague
§  Ca. 1350-1750
§  Affects all ages
§  Episodic occurence with high death rates (15-40% of
population)
Img. 3
§  Transmission by rodents
Larissa von Buol & Salome Bechtler |
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Smallpox
§  Until1978
§  Affects mainly children
§  More continuous, 5 year peaks
(30% case fatality)
§  Transmission between humans
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Modell description
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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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Dominance: plague
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Dominance: smallpox
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Incomplete dominance
§  Heterozygotes have 50% protection
§  Plague: s = 0.09
§  Smallpox s = 0.17
§  Smallpox would need 1135 years
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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 |
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Distribution of the allele
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Agenda: Sickle cell trait
§  Sickle-Cell anaemia
§  Malaria
§  Relation between Malaria and Sickle-cell Trait
§  Observation
§  Discussion
Larissa von Buol & Salome Bechtler |
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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
•  Mosquito-borne infectious disease
•  Female Anopheles mosquito
•  Parasitic protozoans (Plasmodium)
à  Fever, fatigue, vomiting, headaches
Img. 8
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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
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Observation 1
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Observation 2
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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
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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.
§  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: Images
§  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 CCR5Δ32 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 HIVresistance 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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