Determine the Genetic Element on Human Chromosome 9 That Increases Risk for Glaucoma

Human genetic studies show glaucoma is caused by a combination of genetic risk factors. However, few specific changes have been determined. This is severely hampering our ability to identify those at risk of developing glaucoma and developing new treatments. In this study we aim to determine the specific genetic element in a genomic region that shows one of the strongest associations with glaucoma.

The aim of this research is to use mouse models to understand the mechanisms by which a region of the human genome increases risk for glaucoma. Multiple studies have shown that genetic variations in a region on human chromosome 9, containing a number of genes including CDKN2A, CDKN2B and CDKN2B-AS increase risk for glaucoma but the primary reasons behind this are not clear. In the first aim, we will use state-of-the-art genomic methods to identify and better characterize the genetic elements that are present in this region. To do this, we will use mouse models that develop high intraocular pressure. In the second aim, we will create a mouse model that allows us to remove the CDKN2B-AS gene. Unlike many genes, this gene does not code for a protein, but functions to control the expression of other protein-coding genes (such as CDKN2B). With this new mouse strain, we will be able to very precisely remove the CDKN2B-AS gene without disturbing the architecture of the surrounding genes. This work will lay the foundation to understand why the CDKN2B-AS locus modifies risk for glaucoma.