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 Portugal
Isabella was the second child and eldest daughter of King Manuel I of Portugal and his second wife Maria of Aragon. She was named after her maternal grandmother and her aunt Isabella, who had been her father's first wife. Isabella was second-in-line to the throne until the birth of her brother Luis in 1506. However, as the oldest daughter of Manuel I of Portugal, she was a rather attractive candidate for marriage.