Nine new genes determining bone strength have been discovered with a new and rapid functional screening approach, and could provide clues to human skeletal diseases.
An international team of researchers used high-throughput multi-parameter phenotype screening to identify functionally significant skeletal phenotypes in 100 mice engineered such that a single gene had been inactivated in their genome. They assessed mineral content, strength and flexibility of bones, finding nine genes related to bone strength not been previously implicated in bone disorders such as osteoporosis.
“We are developing new ways of finding genes that are essential for normal development of the skeleton, and which maintain the structure and integrity of bone during adulthood,” said Professor Graham Williams from Imperial College London. “These genes will provide new understanding of the mechanisms responsible for bone diseases and may ultimately lead to the development of new treatments.”
Of the nine new genes discovered, five were related to low bone mass, while four were related to a higher bone mass. One of the random genes selected – Sparc – is a well-studied gene whose deletion results in weak, brittle bones. Screening positively identified this gene as affecting bone health and this acted as a well-characterised positive control for the identification of the nine new genes that the study uncovered.
“Our study is an example of where approaching biology without any prior assumptions and looking broadly at the effects of inactivating a gene allows you to find new biological insights that wouldn’t be possible in other, more focussed studies,” said Dr Jacqueline White from the Wellcome Sanger Institute.
The study – published in PLoS – shows loss of function of these genes can disrupt the structure and composition of bone. The disruption can be classified into three different categories; weak and flexible bone with low mineral content like postmenopausal osteoporosis; weak and brittle with low mineral content similar to osteogenesis imperfect; and high bone mass, which is rare in humans.