Yeast model puts genetic code variations in context for development of POAG

Hum Mol Genet. 2009:18(7):1276-1287.

In a study that further demonstrates the range of circumstances necessary for a genotypic expression to lead to phenotypic pathology, researchers have identified a possible co-factor in the genetic cause of primary open-angle glaucoma.

While previous research has identified a possible genetic link to primary open-angle glaucoma (POAG) in the WDR36 gene, rare variants in that gene have been identified both in POAG patients and healthy subjects. Therefore, it may be likely that some sequence alterations are causative of ocular pathology, while others are innocuous.

The researchers created a model using yeast Utp21p, which is similar to WDR36. As well, Utp21p is part of the small subunit processome complex and is integral in the development of 18s ribosomal RNA (rRNA).

Sequence variations thought to be associated with POAG introduced to UTP21, the code sequence for protein Utp21p, did not alter cell viability. However, when domain STI1 was disrupted, five of 11 samples tested had either elevated or decreased cell viability, which corresponded to pre-rRNA levels in the cell.

According to the study, the findings confirm the role of WDR36 in glaucoma formation, but only in context of other genetic variations.