American and British scientists have made several key discoveries that dramatically narrow their long search for the elusive gene that causes cystic fibrosis, the most common fatal genetic disease in the Western world. The new findings are also expected to lead soon to a diagnostic test for those at highest risk of getting the disease.
Cystic fibrosis causes the body to produce abnormally thick mucus that clogs the lungs and digestive system. The average life expectancy is age 21. There have been advances in treating the symptoms, but no treatment or cure for the disease.
In a series of four papers reported in this week's issue of Nature, three teams report independently for the first time that the cystic fibrosis gene is located on chromosome 7, one of 23 pairs of gene-carrying structures found in each human cell.
Two of the teams identify new genetic markers that may signal the presence of the cystic fibrosis gene and are physically close enough to apply new molecular techniques to pinpoint it. Identification of the gene could lead toward treatments for the underlying biological defect.
In the meantime, scientists say that these new markers may mean speedy development of a diagnostic test that might be used in prenatal diagnosis to see if a fetus is likely to have the disease or in testing adult family members to see if they are carriers before they attempt to have children.
There are at least 30,000 cystic fibrosis patients in the United States; about one in 2,000 infants is born with the disease. They must inherit a defective gene from both parents to get it. About 10 million Americans -- one in 20 Caucasians -- are thought to be asymptomatic carriers of the defective gene.
The newly reported discoveries "signal the beginning of the end of the hunt for the cystic fibrosis gene, defects of which are responsible for the disease," says an enthusiastic commentary by Nature's deputy editor, Peter Newmark.
The recent findings have "outpaced the previous advances over the past 25 years in cystic fibrosis," said Dr. Robert J. Beall, of the Cystic Fibrosis Foundation, which funded part of the research.
While it has been known for nearly four decades that cystic fibrosis is likely the result of a defective gene, only in recent years have scientists been able to apply revolutionary molecular techniques to probe the genetic material for signs of it.
The hereditary material of the body is carried in DNA, or deoxyribonucleic acid, which forms about 100,000 genes that are carried on 46 chromosomes found in each cell. Until recently, scientists did not know where among them the cystic fibrosis gene might be found.
Initial signs of success came in late summer, and last month researchers from Boston's Collaborative Research Inc. and Toronto's Hospital for Sick Children reported that they had located a rough genetic marker that singled out the 1 percent of all human genetic material containing the cystic fibrosis gene. It comprised about 30 million of the 3 billion or so basic units that make up human DNA.
The new papers by the Boston and Toronto group and two other groups report that the gene is "now certain" to be on chromosome 7, Nature magazine says. Most importantly, collaborative efforts by researchers at the University of Utah and the National Cancer Institute, as well as a separate international effort headed by scientists at the University of London's St. Mary's Hospital, have found two new genetic markers that appear to be at least 10 times closer to the target gene, within a few million units.
This is significant, Nature notes, because the new markers may have payoffs in prenatal diagnosis and screening for the disease, even before the cystic fibrosis gene is located. Both Utah and NCI researchers emphasized, however, that this would only be applicable to families in which there is a known history of the disease, but not specific enough to use as a screening test in the general population.
"Six months to a year from now, I'm confident that this test will be available," said Utah's Dr. Ray White, although it would be premature to use until technical refinements are achieved.
The search for the actual cystic fibrosis gene, he estimated, could take at least a "year or two" or longer.
The new genetic probe was successfully tested by White on 25 families afflicted with cystic fibrosis.