Anton Persikov, PhD
Lewis-Sigler Institute for Integrative Genomics
Princeton University 

Research Funded by Ehlers-Danlos National Foundation

Glycine mutations in type III collagen gene often lead to the Vascular Type of Ehlers-Danlos syndrome. My study showed that these substitutions result in destabilization of collagen triple helix, which varies depending on the amino acid residue replacing for glycine, as well as amino acid environment of the mutation site. The level of this destabilization may determine whether mutation will or will not lead to disease. In particular, when proline residue is found next to the mutated glycine, the triple helix destabilization is more dramatic, leading more frequently to pathological EDS phenotypes. The least destabilizing mutations, when glycine is replaced by alanine, cysteine or serine, and these residues are not followed by proline, lead to minimal destabilization of the collagen and normal phenotypes. I will continue studying how mutations observed in EDS affect collagen ability to bind other molecules in extracellular matrix. Understanding of molecular basis for EDS together with modern machine learning methods will allow prediction of phenotype from the knowledge of genotype. In another words, from DNA analysis it will be possible to predict whether alterations in collagen gene will or will not lead to disease.