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They established relations with the Coosa chiefdom, as they recorded assisting the Coosa in a raid against the rebellious province of Napochín, in what is now known as Tennessee.Exposed to new Eurasian infectious diseases, these mound builder peoples suffered high mortality rates, as they lacked immunity; within 20 years the community was abandoned.There is some debate over whether Hernando de Soto was the first Spanish conquistador to encounter Native Americans in the area now known as Rome, but it is usually agreed that he passed through the region with his expedition in 1540.In 1560, Tristán de Luna sent a detachment of 140 soldiers and two Dominican friars north along de Soto's route.
National leaders such as Major Ridge and John Ross resided here before Indian Removal.
It is the largest city in Northwest Georgia and the 19th largest city in the state.
Rome was built at the confluence of the Etowah and the Oostanaula rivers, forming the Coosa River.
A Cherokee village named Chatuga was settled in this area during the late eighteenth century, in the period of the Cherokee–American wars (1776–94) during and after the American Revolutionary War.
The Cherokee referred to this area as "Head of Coosa".