By inspecting the sequence of all 3 billion "letters" that make up the genome of a single person affected with a rare, inherited disorder, a Johns Hopkins and Duke University team ferreted out the single genetic mutation that accounts for the disease.
Reporting their results in the June 17 issue of PLoS Genetics, the team says an altered version of the gene PTPN11 is the cause of metachondromatosis, a disorder characterized by bony growths, often on the hands and feet.
The study, the scientists say, demonstrates that new, whole-genome sequencing technology can efficiently and accurately lead investigators to the identification genes that cause Mendelian diseases those caused by mutations in a single gene and passed on according to classic genetic patterns.
The traditional way of collaring a Mendelian disease-causing gene entails time-consuming and labor-intensive genetic analyses of numerous related individuals across generations. Known as "linkage," this approach depends on collecting families, especially large families with multiple affected members. This can be difficult and time consuming and often does not have sufficient resolution to identify the responsible gene. In fact, the definitive catalog of genes and disorders maintained at Johns Hopkins, Online Mendelian Inheritance in Man (OMIM), lists more than 1,500 disorders for which linkage studies have identified a large genomic region but have failed to pinpoint the responsible gene.
The failures were often due to the absence of enough related and affected individuals to provide linkage evidence of sufficient strength and resolution to identify the genes responsible for rare inherited diseases. Another weakness of linkage studies is that an affected individual may be so mildly affected that they are erroneously classified as unaffected, thereby skewing study results.
Success for metachondromatosis came when researchers combined a linkage study of 11 family m
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions