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The usual answer is Infectious Diseases that Columbus and Co brought with them from Europe - diseases that had previously been unknown in the Americas and against with the Native Americans had therefore not built up immunity or even resistance.

By the way, I wouldn't call that an American holocaust as was not deliberate killing.

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Q: When discussing the question of an American holocaust your text concludes that most of the terrible decimation of the Native American population after 1500 resulted from?
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