Using new, whole-genome sequencing technology coupled with classic methods of genetic investigation, scientists at Duke University, along with colleagues at Johns Hopkins, have discovered two mutations in the same gene that seem to cause metachondromatosis in humans.

This is a rare, heritable disease that leads to bony growths, mostly on the hands and feet. The discovery, published June 17 in the open-access journal PLoS Genetics, was accomplished by sequencing the entire genome of just one individual from a family with multiple cases of metachondromatosis, a feat that until recently would not have been possible.

In the past, determining the genetic causes of rare heritable diseases could be time-consuming and costly, and for some cases, simply proved impossible. In the case of metachondromatosis, next-generation sequencing quickly implicated a deletion in the gene PTPN11, and tests confirmed that each individual affected with metachondromatosis in the studied family carried this mutation.

The findings may also reveal the molecular basis of other diseases, like Maffucci syndrome and Ollier's disease, since individuals with those disorders have similar physical characteristics as people with metachondromatosis.

Furthermore, David Goldstein, Director of the Centre for Human Genome Variation at Duke and senior author of the paper, said: 'One exciting feature of the study is that similar modest linkage evidence is sometimes observed for common diseases too, suggesting that such family-based sequencing may also prove valuable for the more difficult-to-study common complex diseases.'

The researchers say the next steps are to investigate the biological effects of the mutations and whether related syndromes are influenced by the same gene. These findings suggest that next-generation sequencing may allow the rapid resolution of many of the familial diseases that have so far eluded researchers, and provide encouragement for sequencing-based studies of common disease.