An Australian researcher has found the third and final missing piece in the genetic puzzle of an unusual form of hemophilia, more than 20 year after he discovered the first two pieces.
Professor Merlin Crossley, of the University of New South Wales, and his international team studied the blood-clotting disorder, hemophilia B Leyden, which is unusual because symptoms improve after puberty.
The results, published in The American Journal of Human Genetics, explain how more than half of the cases of this rare, hereditary bleeding disorder occur, and could help improve understanding of other conditions such as thrombosis.
The find also demonstrates the importance of curiosity-driven research, says Crossley, who is dean of science at UNSW.
"Science is advanced by people who get caught up in puzzles that are important to them and they never forget them. Curious investigators never give up," he says.
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 hemophilia B Leyden, carried out at the University of Oxford in the late 1980s.
People with the disorder have three different categories of mutations in the gene that produces clotting factor IX, which prevents excessive bleeding. Crossley was able to work out how two of them operate, while at Oxford.
He found the two sets of mutations prevent two key proteins from attaching to the DNA, which turns the gene off as a result. Symptoms improve in young men after puberty because a different protein that responds to the hormone testosterone is able to bind to the DNA and boost the gene's production of clotting factor IX.
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 others at UNSW, including Dr Alister Funnell, and researchers in the UK, New Zealand and Belgium, to show the newly identified protein, ONECUT, was the missing piece in the puzzle of hemophilia B Leyden, which affects about 80 families worldwide.
The original research allowed families to be informed that their children were likely to get better after puberty.
While the new research will not alter the method of treatment for people with hemophilia B Leyden, it could lead to new approaches to regulating genes in general for experimental, or ultimately, therapeutic purposes.
"Understanding the molecular regulation of the coagulation factor IX gene may aid in the development of therapies for other blood-clotting disorders such as thrombosis," says Funnell.
University of New South Wales: http://www.unsw.edu.au
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Scientists never understood what became of the Paleo-Eskimos who once peopled the north. Now they know—and there's new reason to miss them
NOAA whittles down initial list of 66 species to be covered by Endangered Species Act
Unusual fish with lungs have developed walking techniques and bodies like those of the ancestors of four-legged animals after being raised on land
A new atlas draws on thousands of records reaching back to the 18th century and describes more than 9000 species, ranging from microbes to whales
The frailty of remembrance might have an upside: When a memory is recalled, two research teams reported on Wednesday, it can be erased or rewired so that a painful recollection is physically linked in the brain to joy and a once-happy memory to pain.
There were some fine vintages 3,000 years ago, and a new study reveals how ancient mixologists made them finer still
Growing nerve tissue and organs is a sci-fi dream. I met the pioneering researcher who grew eyes and brain cells
Australian researchers want tourists to send in photos of flukes so they can track eastern humpback whale movements
Scientists produce a simple mathematical model that explains how a single sheepdog can herd a large number of sheep.
A North Texas family, who discovered the skeleton of a 20,000- to 40,000-year-old mammoth while mining through sediment on their farm, is preparing to turn over the remains to a local museum.