"This whole-genome study, which took only two months, got us to a place where otherwise we wouldn't have arrived very quickly, if ever," says David Valle, M.D., Henry J. Knott Professor and director of the Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "It's a great example of the power of a broad, agnostic approach."
By comparing the one whole genome of the affected individual with eight non-affected control genomes as well as to a database of single-letter variations known to occur in more than one percent of the population, and to other sequencing data, the researchers came up with a list of 100 possible candidate genes. These were analyzed in light of the linkage evidence which, although modest, allowed the team to narrow its search for variants to just a fraction of the genome and narrowed the list to half a dozen genes. Then they combed the literature to understand what was known of the biological function of these candidates, looking for any that might be involved in bone development.
Nara Sobreira, a graduate student in human genetics at Johns Hopkins and a lead author of the study, found that lots had been published about one of the six genes, PTPN11. Mutations in this gene made it hyperactive, causing Noonan syndrome, a genetic disorder that prevents normal development in various parts of the body, including the skeleton.
This newly discovered mutation or altered version involved a so-called "deletion" in which a piece of the genetic code is missing and like
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Johns Hopkins Medical Institutions