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The absence of the selection pressure malaria. Without selection, in the form of the malarial environment, the sickle cell allele will be lost in the overall US population. Even the heterozygous condition is somewhat deleterious and, statistically without malarial selection pressure the allele will be selected out.

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Q: What was primarily acting to change the frequency of the sickle-cell allele in the overall U.S. population?
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