The University of New South Wales’ (UNSW) Dean of Science, Professor Merlin Crossley, has tracked down the third and final missing piece of the genetic puzzle of an unusual form of haemophilia, over 20 years after he first discovered the first two pieces.

The discovery promises to improve our understanding of other blood-clotting conditions, such as thrombosis.

Professor Crossley and his international team, including UNSW's Dr Alister Funnell, studied the blood-clotting disorder, haemophilia B Leyden, which is unusual because symptoms improve after puberty.

Crossley spotted the final genetic clue two years ago, when he was on an aeroplane, marking a young researcher’s PhD project. Data in the thesis reminded him of his own PhD project on haemophilia B Leyden, carried out at the University of Oxford in the late 1980s.

Crossley, and many other researchers after him, tried to find the key protein associated with the third group of mutations, which accounts for more than half the cases of the disease, but it remained elusive. “Things moved on, but I never forgot,” he says.

Two decades later, on the plane, he realised the young researcher was describing a DNA-binding site for a newly discovered protein that had a very familiar ring to it. “I remembered it. It was the same sequence as for the binding site for the third group of mutations,” Crossley says.

He joined forces with other researchers at UNSW, in the UK, New Zealand and Belgium, to show the newly identified protein, ONECUT, was the missing piece in the puzzle of haemophilia B Leyden, which affects about 80 families worldwide.