Cheltenham Gold Cup winner Synchronised and Junior are both now single-figure prices to win the Grand National at 9/1 following the news that former favourite Prince De Beauchene will miss out on a trip to Aintree.
The duo were previously 10/1 behind Prince De Beauchene, who was well fancied after seemingly getting in off a low weight for Aintree following a victory in a traditional Grand National trial at Fairyhouse.
However, some problems at home led trainer Willie Mullins to take the horse to the vet and the finding was that Prince De Beauchene has a stress fracture around his hip area, which will require about eight weeks of rest.
The news is unfortunate for all concerned and if the horse was to return for another crack next year, it is almost certain that he will be treated much more harshly by the handicapper.
For owner Graham Wylie, his only solace is that he does have another of the 2012 Grand National runners in On His Own, who is also trained by Mullins.
On His Own is 20/1 to win the Grand National and assuming his inexperience is not too much of a hindrance, he could go close.
Jockey Ruby Walsh is another impacted by developments as it was strongly believed that he would ride Prince De Beauchene and so now he will have to choose between On His Own or Seabass, who is trained by his father Ted.
With still a week to go until Aintree, there remains a possibility that other big fancies will not line up and there are suggestions that 16/1 fancy Sunnyhillboy is a doubt.
Like Synchronised, Sunnyhillboy was a winner at the Cheltenham Festival and although little is known of his current condition, there is a chance that he may not have fully recovered from his exploits last month.