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Since the Targaryens have been in Westeros for about 300 years, it seems odd that there is only one (verified) of the bloodline left, what happened to the rest?

I think there were but eight Targaryens in 'living memory': Aemon (maester) Aerys; Rhaella; Rhaegar; Viserys; Daenerys; Rhaenys; Aegon

Was their inbreeding so extreme to result in so few numbers? What about all the bastards/Blackfyres or those with confirmed close heritage ?

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    Ok; Blackfyres have been coming and going for about 100 years now - the last of which was Maelys "The Monstrous" (slewn by Barristan) - see the various Blackfyre Rebellions; then there was the Spring Sickness which resulted in te death of many, before that there was the Dance if Dragons; and most recently the Tragedy at Summerhall. You are correct that their in-breeding has whittled their numbers to a very low number. Bastards and off-Shoot branches (Velaryons and Plumms) are becoming a rarity too. – Möoz Apr 7 '15 at 23:26
  • @Mooz In the 'History and Lore' section of the season 1 blu-ray, Charles Dance (Tywin) has line saying that during the Sack of King's Landing be 'removed the remnants of the Royal family as quickly and efficiently as possible'. Is there canon to support this? – Gridley Quayle Apr 7 '15 at 23:43
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    There is another Targaryen: (Maester) Aemon. – user8719 Apr 8 '15 at 7:01
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    @GridleyQuayle Tywin had Rhaegar's children (Rhaenys and Aegon) put to death after the sack. Remember Prince Oberyn yelling at The Mountain? That's what all that was about - Rhaegar was married to Oberyn's sister (Elia Martell), and Gregor killed her children at the order of Tywin. Tywin had come late to the war and used this ploy to curry favour with Robert Baratheon. – Möoz Apr 8 '15 at 9:31
  • @Mooz For some reason I thought she was being guarded outside King's Landing. Got Elia confused with Lyanna in the Tower of Joy. Aerys kept Elia to ensure that Dorne stayed in line correct? – Gridley Quayle Apr 8 '15 at 12:18
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Short answer: they were killed through war, disease and horrible disasters.

Longer answer:

The 300 years of Targaryen rule has been extremely bloody. And while the people of Westeros stood no chance against the dragon riders, the Targaryens were not immune against themselves. Several incidents served to whittle down the Targaryen clan (which was never very large in the first place).

The Dance of the Dragons: The first Targaryen civil war. When King Viserys I died, a successsion crisis erupted between his heir apparent Rhaenyra Targaryen and her half brother Aegon (the eldest male child). The Targaryens (and Westeros) were split in half and a bloody war ensued that saw both sides utilizing dragons. In the end Aegon II was crowned king, but not before both sides suffered great losses in both Targaryens and dragons. It was this war and it's immediate aftermath that lead to the decline of the Targaryen dragons You can read more about that war in the prequel novella The Princess and the Queen.

The Blackfyre Rebellion: The second Targaryen civil war. Just before King Aegon IV died he legitimized a number of his bastards, chief among them Daemon Blackfyre. When Aegon died, many noblemen could not stomach his bookish heir Daeron II and flocked around the classically martial Daemon who claimed the Iron Throne for himself. The rebellion was quelled, but again not without serious loss of life. Heirs of Blackfyre would continue to plague Westeros, later even managing to kill King Maekar I.

The Great Spring Sickness: A plague that ravished Westeros leaving tens of thousands of dead in its wake. Amongst the victims were King Daeron II and several Targaryens including several of the king's grandsons.

The Tragedy of Summerhall: A mysterious event that killed several Targaryens, including King Aegon V and his heir. Fandom speculated that it was an attempt to revive dragons that went horribly wrong.

Robert's Rebellion: 'Nuff said.

  • Good point on "the Targaryen clan...wasn't too large to begin with". – Möoz Apr 8 '15 at 9:33
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There were several reasons why only a few Targaryens remained after 300 years:

  • The Targaryen custom of incestuous marriage (including brother/sister) meant there were fewer branches of the family tree to carry on the name. In the real world, members of incestuous family lines are likely to have harmful genetic conditions, which may make them infertile or cause them to die at a young age.
  • In times of war, members of the family might have died young in battle, before they could have (as many) children.
  • Some male family members would have become maesters (like Aemon), septons, or joined the Night's Watch, so they would be unable to have legitimate children.
  • Rebels against the King, such as the Blackfyres, would have been executed. This would have thinned out the ranks further.
  • The family name only descends through the male line. For example, Robert Baratheon's claim to the throne came from his Targaryen grandmother -- but he was still a Baratheon, not a Targaryen.

For a historical example, look at the Habsburg Kings of Spain from 1516-1700. They lasted less than 200 years before dying out in the male line. Inbreeding was a significant contributor to their demise. The Habsburgs didn't practice sibling marriage, but marriages between first cousins were commonplace, and over the generations this led to an extreme degree of inbreeding.

If anything, it's remarkable the Targaryens have lasted so long -- they seem far less debilitated by inbreeding than one would expect. This is presumably some effect of their magical or Valyrian heritage.

Even without extreme inbreeding, royal dynasties did disappear for the other reasons mentioned above. For example, the Valois family ruled France for 231 years (1358-1589), but eventually died out in the male line and was replaced by the house of Bourbon.

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