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Western expansion under the guise of "Manifest Destiny" took the final toll on the Natives. The idea that the Eastern colonies were ordained by God to claim for the American nation all the the lands between the Atlantic and Pacific Oceans. But there were numerous actions that took serious tolls along the way...the French Indian War had tribes pitted against each other for the purpose of European expansion into their lands by European countries, every treaty that was made and broken by the Americans was damaging, as the European/non-Native Americans populated the Eastern states tribes were pushed onto the plains (the Sioux were originally habitants of the Appalachian country). Every massacre...Sand Creek, the Wapelleta Massacre, Wounded Knee and the many other massacres that were waged under the white flag of the American government. The simple fact that the countries in Europe were overpopulated and the whites of that descent had a chance to sail to and populate the "New World" while bringing their totalitarian culture with them has been of the most serious of tolls. Are you looking for specific examples, or just a general understanding of what happened to the Native cultures during European expansion?
European expansion in the guise of a new nation. Like all world tribes, natives become casualties of globalization no matter what era of human history.
Westward expansion. They were forced out of their homelands onto reservations and many died.