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The Gamma Quadrant is a term designating a quarter of the Milky Way Galaxy, encompassing most of the Dominion, who control most of the quadrant. Earth is approximately 30,000 light years from the closest point of the Gamma Quadrant. (Star Trek: Deep Space Nine)
After discovering the wormhole, several Alpha Quadrant races, including the Vulcans, Humans and Klingons, explored the Gamma Quadrant, using Starfleet space station Deep Space 9 as a base of operations. (DS9: "A Man Alone", "Move Along Home", "Vortex", "The Sword of Kahless", "Q-Less") The Bajorans and Klingons even set up colonies in the Gamma Quadrant, with the Bajoran colony New Bajor being wiped out by the Jem'Hadar in 2370. (DS9: "Dramatis Personae", "The Storyteller", "Crossover", "The Jem'Hadar")
In 2370, Starfleet send the USS Prospect to make first contact with the Founders, but the ship barely escaped a Jem'Hadar attack, with Captain John Greene ordering a saucer separation, detonating the stardrive section to destroy the Jem'Hadar attack force. (Star Trek: The Prospect Chronicles) The Deep Space 9 crew, aboard the USS Defiant, made the first successful first contact with the Founders in early 2371. (DS9: "The Search, Part I", "The Search, Part II")
In late 2371, the Romulan Tal Shiar and Cardassian Obsidian Order launched a pre-emptive strike against the Founders, attempting to destroy the Founders' homeworld. They failed. (DS9: "Visionary", "The Die Is Cast")
In that same year, the experimental Starfleet starship USS Rutherford, testing a new folded space drive prototype, faced a fault in the drive, jumping to the Gamma Quadrant. Starfleet sent the Special Operations starship USS Prospect-A to investigate, and the Rutherford was found abandoned. The Prospect-A crew destroyed the Rutherford to stop it falling into enemy hands. (Star Trek: The Prospect Chronicles: "Directive")
To stop the Dominion progression into the Alpha Quadrant, the Federation placed mines around the Bajoran wormhole's entrance in 2373: an act contributing to the start of the Dominion War. (DS9: "Call to Arms", "Sacrifice of Angels", "Tears of the Prophets")