Sickle-Cell Anemia & other malaria related human polymorphisms

Questions to answer about the beta globin gene sequences.

1. The gene sequences of the typical and sickle-cell allele code for identical proteins except
   for one amino acid (highlighted – note that a single letter amino-acid code is commonly
   used). There is one additional sequence difference between the alleles (also highlighted).
   Can you suggest what the association (called “linkage disequilibrium”) of these two
   changes in all of the sequences of the sickle-cell allele might mean?
2. This additional DNA base change illustrates an important feature of the genetic code.
   Explain. There are two other features of eukaryote genes illustrated by (i) the * and (ii) the
   xxx. What are they?
   Questions to answer from Allison (1964) “Polymorphism and natural selection in human
   populations”.
3. Why was the relatively high frequency of sickle-cell allele in parts of Africa unexpected,
   causing him to propose in 1954 that resistance to malaria may favor the allele?
4. By 1954, Allison had confirmed his hypothesis. How did he do this? (Bear in mind that
   natural selection responds to differences in fitness). Pay particular attention to Tables 1, 2
   & 3, and Figures 1 & 2. Come prepared to discuss how these data were analyzed.
5. Which two factors does Allison consider to account for the low frequency of sickle-cell
   trait in the African American population?
6. What do the positive (Fig. 3 with Fig 6 showing roughly the same thing for a different
   region) and negative correlations (Figs 4 & 5) suggest? Background information: G-6-PD
   deficiency, and the mutant beta-hemoglobin alleles HbβC and HbβT (causing βthalassemia) all confer some resistance to malaria.