![Page 1: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/1.jpg)
| |
CCR5-Δ32 deletion allele and sickle cell trait
22.09.15 Larissa von Buol & Salome Bechtler 1
Polymorphism and disease resistance
![Page 2: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/2.jpg)
| |
§ 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
![Page 3: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/3.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 3
CCR5-receptor and HIV-1
Img. 1
![Page 4: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/4.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 4
Distribution of the allele
Img. 2
![Page 5: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/5.jpg)
| |
§ Ca. 1350-1750
§ Affects all ages
§ Episodic occurence with high death rates (15-40% of population)
§ Transmission by rodents
22.09.15 Larissa von Buol & Salome Bechtler 5
Bubonic plague
Img. 3
![Page 6: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/6.jpg)
| |
§ Until1978 § Affects mainly children
§ More continuous, 5 year peaks (30% case fatality)
§ Transmission between humans
22.09.15 Larissa von Buol & Salome Bechtler 6
Smallpox
Img. 4
![Page 7: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/7.jpg)
| |
§ 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)
22.09.15 Larissa von Buol & Salome Bechtler 7
Modell description
![Page 8: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/8.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 8
Dominance: plague
Img. 5
![Page 9: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/9.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 9
Dominance: smallpox
Img. 6
![Page 10: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/10.jpg)
| |
§ Heterozygotes have 50% protection
§ Plague: s = 0.09
§ Smallpox s = 0.17
§ Smallpox would need 1135 years
22.09.15 Larissa von Buol & Salome Bechtler 10
Incomplete dominance
![Page 11: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/11.jpg)
| |
§ Smallpox affects younger people (reproductive potential!)
§ Smallpox existed until 1978 (start of AIDS)
§ HIV and poxvirus: disease similarities
§ Geographical distribution
22.09.15 Larissa von Buol & Salome Bechtler 11
Discussion
![Page 12: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/12.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 12
Distribution of the allele
![Page 13: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/13.jpg)
| |
§ Sickle-Cell anaemia § Malaria § Relation between Malaria and Sickle-cell Trait
§ Observation
§ Discussion
22.09.15 Larissa von Buol & Salome Bechtler 13
Agenda: Sickle cell trait
![Page 14: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/14.jpg)
| | 22.09.15 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
![Page 15: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/15.jpg)
| | 22.09.15 Larissa von Buol & Salome Bechtler 15
Malaria
Img. 8
• Mosquito-borne infectious disease
• Female Anopheles mosquito • Parasitic protozoans (Plasmodium)
à Fever, fatigue, vomiting, headaches
![Page 16: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/16.jpg)
| |
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
22.09.15 Larissa von Buol & Salome Bechtler 16
Relation between Malaria and Sickle-cell Trait
![Page 17: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/17.jpg)
| |
22.09.15 Larissa von Buol & Salome Bechtler 17
Observation 1
Img. 9
![Page 18: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/18.jpg)
| | 22.09.15 Larissa von Buol & Salome Bechtler 18
Observation 2
Img. 10
![Page 19: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/19.jpg)
| |
§ 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
22.09.15 Larissa von Buol & Salome Bechtler 19
Discussion
![Page 20: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/20.jpg)
| |
§ 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
22.09.15 Larissa von Buol & Salome Bechtler 20
Sources
![Page 21: Polymorphism and disease resistance · Bubonic plague vs. smallpox ! Model description ! Dominant vs. incomplete dominace ! ... Evaluating plague and smallpox as historical selective](https://reader035.vdocuments.mx/reader035/viewer/2022071608/6146e8aff4263007b1357b1c/html5/thumbnails/21.jpg)
| |
§ 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.
22.09.15 Larissa von Buol & Salome Bechtler 21
Sources: Images