The discovery, which is reported in the April 10 advance online section of Nature Genetics, proves that genes behind very rare inherited diseases can now be found, offering excellent opportunities to strengthen understanding of craniofacial and limb development, health and disease beyond the rare disease itself, say the researchers.
Because of advances in technology and computer analysis, the researchers were able to find the Roberts gene, called ESCO2, by studying samples from just 15 Roberts syndrome families from Colombia, Turkey, Canada and Italy and to provide insight into its biological effect.
"For decades now, we've known that the appearance and number of chromosomes were abnormal in people with Roberts syndrome, but we hadn't been able to figure out why or how," says Ethylin Jabs, M.D., a professor in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins. "Just within the last few years have the genetic techniques, the genomic information, and the computer analysis become powerful enough to find the genetic mutations behind a disease as rare as Roberts."
Some of the techniques they used -- such as that to make many copies of DNA from a small sample -- have been around in some form for more than a decade. But others are much more recent developments. For example, the researchers found important genetic changes in part by comparing different species' genetic sequences, most of which were published only within the last four years.
"In 1989, we were collecting samples and characterizing the chromosome problem in cells from people with Roberts syndrome," Jabs remembers. "