final exam-genetic mech of disease resistance.txt

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final exam-genetic mech of disease resistance.txt
2013-04-29 00:42:48
final exam genetic mech disease resistance

final exam-genetic mech of disease resistance.txt
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  1. Name the two genes associated with cell surface receptors talked about during lecture and the disease each confers resistance to. Focus your answer on the how the genes are similar, how they are different, and explain how each confers resistance to its disease.
    • 1. Cystic fibrosis transmembrane conductance regulator (CFTR) gene: confers resistance to typhoid fever
    • 2. South Asian ovalocytosis (SAO) gene: confers resistance to strand of cerebral MALARIA
    • BOTH arise from deletions: CFTR from 3 nucleotide at pos. 508. SAO from 27bp deletion in band 3 protein.
    • DIFF in action: CFTR deletion PREVENTS entry of typhoid bacteria into body. SAO deletion causes CONFORMATIONAL change to RBCs to increase rigidity of membrane, making it difficult for MALARIA parasite to attach and enter cell.
  2. Explain the differences between individuals with the active and inactive forms of the CASPASE-12 gene.
    • Most of global pop. expresses INACTIVE form: STOP codon at aa 225.
    • These individuals thought to be RESISTANT to systemic inflammatory response syndrome (sepsis).
    • ACTIVE form: these full length caspase protein produces LOWER cytokine levels after LPS stimulation.
    • This leads to LOW initial immune response, and HIGH danger of immune overreaction and sepsis if bacterium comes into cell
  3. In the paper by Xia et al. 2011, one of the final conclusions of the paper was that they believed they identified an effective anti-HIV siRNA gene to target viral RNA. Do you think their data supported this conclusion, why or why not? If not, what would you do to provide further experimental evidence?
    • The data showed that in cells treated with antiHIV adenovirus, p24 expression remained at a low level, while it increased with untransduced cells
    • HOWEVER, the data did not show a control using a copy of the adenovirus without CCR5 siRNA gene removed. This would help to see if CCR5 siRNA was directly responsible for this reduction of p24 expression, or if it was another portion of this plasmid that was transduced.
  4. What disease does Sickle Cell Anemia (SCA) mutation provide resistance to, what gene is affected, and what is the mode of inheritance (i.e. dominant vs. recessive and autosomal vs. sex-linked)? Specifically, how does the SCA mutation provide this resistance? Is there any fitness cost to being heterozygous for the SCA mutation?
    • SCA mutation provides resistance to MALARIA
    • It effects the gene for HEMOGLOBIN by either a point mutation or a change in one nucleotide.
    • It is an AUTOSOMAL RECESSIVE genetic blood disorder
    • If a carrier has both copies of the mutated gene: SCA
    • If carrier has only one copy: no SCA, but MALARIA RESISTANT
  5. Explain the difference between being Duffy-negative and Duffy-positive specifically relating to Plasmodium falciparum malaria and P. Vivax? In what area(s) of the world do we see the highest frequency of the Duffy-negative allele?
    • Duffy-negative: RESISTANT to infection by P. Vivax because the Duffy antigen receptor is missing and P. Vivax depends on this receptor to gain entry to cell. BUT…
    • Duffy-negative: More SUSCEPTIBLE to P. falciparum malaria because the Duffy receptor needed to protect and help kill the Plasmodium falciparum parasite.
    • Duffy negative seen most in sub-Saharan African populations
  6. The paper by McMorran, et al. 2012, described the involvement of two molecules involved in the ability of platelets to kill Malaria, what where they? What role does each molecule play in killing the parasite Plasmodium falciparum?
    • In killing Plasmodium falciparum, two molecules are involved:
    • 1. Platelet factor 4 (PL4): penetrates RBCs infected by the parasite and kills it directly.
    • 2. Duffy antigen: Serves as a docking site for PF4 to attach and enable it to attack parasite.
  7. The Sickle Cell Anemia (SCA), Southeast Asian Ovalocytosis (SAO) and Duffy-negative (Fy-) mutations all confer resistance to malaria. What are the proteins that these genes code for, what are their normal functions and what are the mechanisms by which they confer resistance to malaria?
    • SCA: hemoglobin protein is affected from point mutation. Normal role of hemoglobin is to carry oxygen from lungs to rest of the body. The mutation here causes resistance to malaria
    • SAO: the band3 protein mutation is what it encodes. Normal function of Band 3 is a transport protein mediating Chloride to bicarbonate exchange across plasma membranes in erythrocytes. By blocking Band 3, Less clustering of this protein is possible due to rigid structure of RBC, so of this makes it more DIFFICULT for malaria to ATTACH and enter cell.
    • Duffy-Neg: Protein, normally functioning by acting as a receptor for chemicals secreted by blood cells during inflammation…however it also functions as receptor for P. vivax and P. knowlesi malaria parasites. When Duffy-neg, no receptor for these malaria parasites to bind to so they are resistant to them.