Thesis ID: CBB001567174

Explaining the Evolution of Common Genetic Disease (2010)

unapi

Valles, Sean A. (Author)


Wade, Michael J.
Allen, Colin
Indiana University
Gliboff, Sander
Wade, Michael J.
Allen, Colin
Lloyd, Elisabeth A.
Gliboff, Sander


Publication Date: 2010
Edition Details: Advisor: Lloyd, Elisabeth A; Committee Members: Gliboff, Sander, Wade, Michael J., Allen, Colin.
Physical Details: 305 pp.
Language: English

My dissertation is primarily a philosophical analysis of the long-standing deadlock among the researchers who wish to explain why certain single-gene genetic diseases occur at elevated rates. Researchers have long struggled to explain why diseases such as Tay Sachs (among Ashkenazi Jews), cystic fibrosis (among European descendents) and Huntington's disease (among populations across the globe) have risen to such high rates. Despite decades of research, the debates surrounding these diseases' evolution have made little progress toward a consensus. After a historical introduction to the literature, I apply a combination of novel and existing philosophical tools to explain why this long-standing deadlock persists. Most importantly, I use three scientific model evaluation frameworks to analyze the strengths and weaknesses of the existing models/explanation of common genetic disease rates. Two of these frameworks evaluate the models' formal population genetic equations. The third framework, evaluates the models' underlying assumptions about relevant biochemical mechanisms. I find that models assuming the operation of natural selection through heterozygote advantage (as opposed to random non-directed evolutionary forces) have been inappropriately favored by researchers, despite serious empirical weaknesses. I contend that much of the problem can be attributed to the 1954 malaria-resistance (for gene carriers) hypothesis of sickle cell anemia rates, which was so successful that researchers have ever since tried to find analogous models for other common genetic diseases. I also demonstrate the importance of what I term "phenomenon choice," the choice of precisely which problem one wishes to explain, which I show is a surprisingly difficult issue in this literature, and has long contributed to the general confusion in the literature.

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Description Cited in Dissertation Abstracts International-A 71/07, Jan 2011. Proquest Document ID: 725992239.


Citation URI
https://data.isiscb.org/isis/citation/CBB001567174/

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Authors & Contributors
Grodwohl, Jean-Baptiste
Peirson, B. R. Erick
Green, Lisa Anne
Eugene, Earnshaw-Whyte
Veuille, Michel
Sober, Elliott R.
Concepts
Evolution
Natural selection
Population genetics
Biology
Models and modeling in science
Philosophy of biology
Time Periods
20th century, late
20th century
19th century
18th century
Places
United States
Italy
Institutions
Club of Rome
Massachusetts Institute of Technology, MIT
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