John Isner has been forced to withdraw from the Australian Open, which starts next week, because of a troublesome knee injury.
The world number 13 and leading American player reached the fourth round in Melbourne three years ago and admits it is extremely disappointing to miss out this time.
He said: "I've been feeling some discomfort in my knee and have recently learned that I have a bone bruise.
"My doctors have told me that continuing to play on the knee could result in a more serious injury, so I have regrettably decided not to compete in Melbourne and use the time to fully recover."
The latest odds have Roger Federer at 4/1 to win the Australian Open while Andy Murray can be backed at 5/2 to win back-to-back Grand Slam titles following his success at last year's US Open.
Meanwhile, there was mixed news for two British women after Johanna Konta moved into the second round of qualifying for the tournament but Anne Keothavong missed out.
Konta, the British number four, beat Latvia's Anastasija Sevastova 6-3 6-7 6-4 in a marathon match while Keothavong slumped to a disappointing 7-5 7-5 defeat to the American Grace Min.
Konta is currently 153rd in the world rankings and seems certain to soon overtake the former British number one Keothavong who has slipped to 142nd.
Konta will now play Yi-Miao Zhou, the world number 169, on Friday, in the next round of qualifying. Konta is 8/11 to progress while the Chinese woman can be backed at 1/1.
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