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| 1496 |
| | | Diego Columbus, brother of the explorer, establishes the first secure Spanish colony at Santo Domingo | |
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| 1497 |
| | | Henry VII commissions the Italian navigator John Cabot to cross the Atlantic in search of new territories for England | |
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| 1497 |
| | | John Cabot, searching for a trade route to China, probably reaches Newfoundland | |
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| c. 1500 |
| | | The Portuguese establish trading posts in east Africa, on the coast of Mozambique | |
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| c. 1500 |
| | | European diseases bring death on a massive scale to an American population that has no immunity | |
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| 1502 |
| | | Vasco da Gama wins a trading treaty for Portuguese merchants after bombarding the Indian port of Calicut into submission | |
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| 1503 |
| | | The Portuguese set up a trading post on the east African island of Zanzibar | |
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| 1505 |
| | | The Portuguese establish a presence in Sri Lanka, trading in the island's crop of cinammon | |
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| 1510 |
| | | The Portuguese seize Goa and make it their colonial capital in India | |
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| 1511 |
| | | The Portuguese take control of Malacca, in the Malay peninsula, as a base for trade further east | |
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