Bone Abstracts

The massive amount of genetic information made available by next generation sequencing (NGS) has already changed our clinical and scientific approach to skeletal disorders. As one consequence the gap between rare monogenic disorders and common complex disorders is becoming more permeable. On the one hand this is due to the finding that rare variants with larger effect sizes also have significance for common disorders. On the other hand, broader testing strategies reveal a considerable portion of rare disorders among the label of common disorders. As another consequence, analysis of a growing portion of the non-coding genome is becoming normality. The interpretation of non-coding variants is still a major challenge, but important lessons have been learned from the investigations of structural variants. These novel insights would not have been possible without an improved understanding of the 3D structure of the genome, which again was deciphered by NGS technology. At the same time, genome editing has greatly facilitated the generation of models for a better understanding of genetic variants identified by NGS. However, there are still major bottlenecks preventing a sufficient throughput of variant testing. These different points will be highlighted using different skeletal malformations, skeletal dysplasias, and disorders of bone homeostasis as examples.

Disclosure: The authors declared no competing interests.