Do not get infected by hiv ccr5 causes resistance to

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do not get infected by HIV ! CCR5 causes resistance to HIV Frequency of ! CCR5 allele is higher in uninfected individuals Frequency of ! CCR5 genotypes is higher in uninfected individuals ! CCR5 genotypes are lower than expected by chance within the sample of infected individuals door & doorknob (door) (doorknob) Repeat
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To getter a better measure of the association between Δ CCR5 and AIDS we need to know what we should expect if Δ CCR5 had no benefit. To gain more information we can analyze: genotype proportions GENOTYPE CCR5 / CCR5 CCR5 / Δ CCR5 % 89.2 10.8 Δ CCR5 / Δ CCR5 0.0 N N % 582 114 645 78 82.7 16.2 8 0 1.1 (infected) (uninfected) Stronger evidence that Δ CCR5 is protective for AIDS, but we can obtain even more evidence antibody (-) FOR HIV antibody (+) FOR HIV We need to compare Observed vs. Expected -expected when DCCR5 has no benefit, i.e., selectively neutral antibody (-) FOR HIV GENOTYPE CCR5 / CCR5 CCR5 / Δ CCR5 Δ CCR5 / Δ CCR5 antibody (+) FOR HIV Observed Expected ? ? ? % 82.7 16.2 1.1 % Observed ? ? ? Expected % 89.2 10.8 0.0 % --Provides a benchmark for comparison To calculate expected genotype frequencies we need Null Model of NO Natural Selection operating Gamete Pool Zygote Pool (fertilized eggs) Adult Pool Syngamy (sperm & eggs) Survival Gametogenesis Most multicellular organisms cycle between a short-lived haploid stage (gametes) and a long-lived diploid stage (Zygotes & Adults). How does genetic organization map between the stages? (uninfected) (infected) 15 If we know what is in one box, how do we figure out what will be in the other boxes? Suggestive, but can we obtain more convincing evidence (-) for HIV antibody(+) for HIV (N=704) (N=723) infected uninfected antibody proportion of the Δ CCR5 allele 0.054 0.092 We will calculate the expected % by constructing a “null model” that assumes that no natural selection is acting Null models are commonly used in all branches of science Constructing the null model:
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Gamete Pool Zygote Pool Adult Pool Syngamy Survival Gametogenesis Adult Pool Gamete Pool N = Number mating adults The answer requires a null model of no selection: 5 Simplifying Assumptions: 1) Sexual reproduction 2) Diploid adults & short-lived haploid gametes 3) Non-overlapping generations (like annual plants) 4) No evolutionary forces operating -Null Model for comparison (NO mutation, selection, migration, or sampling error) 5) Random mating Consider an arbitrary gene locus: The A-locus with alleles A1 and A2 Definitions: P = proportion of the A1A1 genotype H = proportion of the A1A2 genotype Q = proportion of the A2A2 genotype Zygote Pool Syngamy Survival Gametogenesis
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