Single-Nucleotide Variation in the N-Glycosylation Sequon of Human Genes
Reference #: 2012-034
N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. Single nucleotide variations in the genome also create new N-glycosylation sites and can result in the gain of glycosylation. Investigators at Georgetown University have developed a system and method to perform genome-wide analysis and a database to study the protein structure/functional differences as a result of the changes. A significant number of the proteins identified that have gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. Changes in N-glycosylation modification may also be relevant to the prediction and detection of diseases in patients. For example, highly branched sialylated N-glycoproteins facilitate metastatic cancer diseases.
Invention will improve the design of targeted studies analyzing association of various diseases with non-synonymous single nucleotide variations.
As the genomes of more and more human patients are sequenced, the system and method of the invention will be able to rapidly determine whether any of the single nucleotide variations in a patient’s genome may cause gain or loss of glycosylation that could ultimately result in disease.
Genomic sets of probes will be developed that will be used for rapid diagnostic testing so that the entire genome of a patient need not be sequenced.
Stage of Development
The analysis done thus far indicates the presence of 1091 different proteins that have modified N-glycosylation sequons (loss and gain) due to non-synonymous single nucleotide variations. Some of the identified proteins have gained more than one glycosylation site. Development of specific probes has begun.
No references or resources available.
Provisional patent application filed