Doing some research for a game led me to a potentially deep seam of material - the Trail of Tears was the route taken by the forced migration of five Indian nations into Oklahoma by the American Government at the behest of Andrew Jackson whose ignorance of treaties and court rulings in favour of Indian independence led to the deaths of thousands and spending of millions for their lands.
The Choctaw Trail of Tears
After negotiating a treaty in which about a quarter (some 5000 or so) of their tribe were allowed to remain on land ceded to the US Government, the Choctaw left peacefully, unwilling to be ruled by laws in which they had no part. President Jackson intended the Choctaw removal to be a model one - however it led to nearly 100 years of persecution by neighbouring white settlers.
The first migration in the winter of 1831 led to the migration of about 17,000 Choctaw, of whom 2,500 died due to hunger, harsh weather and being lost in the Lake Providence swamps by incompetent guides - when Alexis de Tocqueville, a French philosopher witnessed the migration, he asked one Choctaw why he was leaving to receive the solemn reply "To be free."
Future removals displaced hundreds until in 1930, only 1,700 Choctaw remained in their native lands around the Mississippi. During this, they were persecuted having '...our habitations torn down and burned, our fences destroyed, cattle turned into our fields and we ourselves have been scourged, manacled, fettered... until by such treatment some of our best men have died.'
The Seminole Wars
In 1832, the Seminole were given an offer to move west and assimilate into the Creek nation, which they had left. This offer was declined based on fears of Creek retribution, a lack of trust in the US Government and lack of authority in the chiefs approached. Some tribes moved west, others did not and the local Florida government chose to send the military in to force the issue.
This met fierce resistance - with the help of escaped slaves, the Seminole killed 107 soldiers, leaving only three survivors from an Army company. For the next 27 years, the Army and Seminoles fought a series of running wars as warriors were bribed with rifles and money to relocate and the Seminole caused dramatic casualties in set-piece battles in the Florida swamps.
After wars costing millions of US dollars, thousands of lives and requiring continued Army presence and raising militias, a series of raids on Seminole villages and significantly increased bribes helped to re-settle the majority of Seminole until only about 200 of them were left in their ancestral lands. They subsequently declined to participate in the governance of Florida.
The more I look at this, the more in awe I am of the authors of Colonial Gothic. You could adopt this story into the system of your choice and come up with encounters and vignettes that would highlight the conflict yet they did a lot of this work for you and the scholarship and research on their Indian player characters is impressive.