Manuel I of Portugal
Manuel's mother was the granddaughter of King John I of Portugal, whereas his father was the second surviving son of King Edward of Portugal and the younger brother of King Afonso V of Portugal. In 1495, Manuel succeeded his first cousin, King John II of Portugal, who was also his brother-in-law, as husband to Manuel's sister, Eleanor of Viseu.
Isabella of Aragon, Queen of Portugal
Manuel later married Isabella's younger sister, Maria of Aragon, who bore him his son and heir, John III. Portugal and Spain were finally united between 1580 and 1640, after Philip II of Spain, Isabella's great-nephew via her sisters, Maria and Joanna, successfully claimed the throne of Portugal as a son of Isabella of Portugal, the daughter of Maria and Manuel.