Differential expression profile prioritization of positional candidate glaucoma genes: The GLC1C locus

Objectives: To develop and apply a model for prioritization of candidate glaucoma genes. Methods: This Affymetrix GeneChip (Affymetrix, Santa Clara, Calif ) study of gene expression in primary culture human trabecular meshwork cells uses a positional differential expression profile model for prioritization of candidate genes within the GLC1C genetic inclusion interval. Results: Sixteen genes were expressed under all conditions within the GLC1C interval. TMEM22 was the only gene within the interval with differential expression in the same direction under both conditions tested. Two genes, ATP1B3 and COPB2, are of interest in the context of a protein-misfolding model for candidate selection. SLC25A36, PCCB, and FNDC6 are of lesser interest because of moderate expression and changes in expression. Transcription factor ZBTB38 emerges as an interesting candidate gene because of the overall expression level, differential expression, and function. Conclusions:Only 1 gene in the GLC1C interval fits our model for differential expression under multiple glaucoma risk conditions. The use of multiple prioritization models resulted in filtering 7 candidate genes of higher interest out of the 41 known genes in the region. Clinical Relevance: This study identified a small subset of genes that are most likely to harbor mutations that cause glaucoma linked to GLC1C.