Gregor Mendel discovered fundamental rules of genetics by raising pea plants. He realized that hidden factors — we now know them to be genes — were passed down from parents to offspring.
It wasn't until the early 1900s, long after Mendel's death, that doctors discovered that some diseases, it turns out, are inherited in humans too — they're Mendelian.
Today, scientists have identified more than 7,000 Mendelian diseases, and many are discovered with screenings of children and adults. But a new study suggests that many disorders go undetected.
With a database of electronic health records and DNA samples, a team of scientists has found that 3.7 percent of patients in a hospital system carried a genetic variant linked to a disease. It's possible that as many as 4.5 percent of cases of apparently nongenetic diseases, from infertility to kidney failure, are the result of such mutations.
The study suggests that it may be possible to catch more of these hidden disorders with a computer program that flags suspicious clusters of symptoms. That would be a big step forward for patients coping with unexplained ailments.
The study, published in Science, represents the first large-scale search of electronic health records for hidden Mendelian diseases. But study co-author Dr. Joshua C. Denny, a biomedical informatics researcher at the Vanderbilt University School of Medicine, suspected that it only revealed the tip of a genetic iceberg. Much larger databases including DNA and records for hundreds of thousands of people are being built, and searching them may uncover many more hidden mutations.
Denny and his colleagues gathered data from Vanderbilt's electronic health records system, which has more than 2 million patients. More than 225,000 volunteered for genetic research. The researchers picked 21,701 patients from the database and surveyed all the symptoms recorded for each one. They then compared the symptoms to those seen in 1,204 Mendelian diseases.
It was a difficult task. These disorders can produce a number of symptoms, and each patient may have a different combination of them. And some symptoms linked to a Mendelian disease may also be signs of other diseases.
Denny and his colleagues developed a scoring system to determine how likely it was that each patient in their study suffered each Mendelian disease.
The team found 807 patients carrying mutations in genes linked to 17 diseases, such as cystic fibrosis or hemochromatosis, which causes iron to build up in the blood. Only eight of these patients received a test that revealed the mutation. In other cases, doctors had tested for the wrong disease. Many times, the doctors hadn't ordered any genetic tests.
The mutations often didn't fit the standard profile for the diseases. Heidi L. Rehm, a molecular geneticist at Brigham and Women's Hospital, said many doctors do not suspect a Mendelian disorder unless their patients have severe textbook symptoms.
Overlooking the genetic causes of diseases can seriously harm patients. Denny said, "There are people here who had kidney and liver transplants that could potentially have been avoided."