Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE

Area of Science:

• Genomics
• Ophthalmology
• Molecular Biology

Background:

• The human macula transcriptome is crucial for understanding retinal function and disease.
• Identifying genes associated with inherited retinal dystrophies (IRDs) is essential for diagnosis and treatment.

Purpose of the Study:

• To create a large-scale, high-throughput annotation of the human macula transcriptome.
• To identify and prioritize candidate genes for IRDs using ocular expression profiles.

Main Methods:

• Generated Serial Analysis of Gene Expression (SAGE) libraries from human retina and retinal pigment epithelium (RPE)/choroid.
• Integrated SAGE and microarray data into the EyeSAGE relational database.
• Validated differential gene expression using quantitative and single-cell RT-PCR.

Main Results:

• Elevated cone photoreceptor-associated gene expression was observed in macula transcription profiles.
• Enhanced tag-to-gene mapping identified alternatively spliced genes.
• The Bardet-Biedl syndrome gene (BBS5) was prioritized as a top candidate for IRDs.

Conclusions:

• The EyeSAGE database is a powerful resource for defining retina and RPE transcriptomes.
• It facilitates the identification of retina-specific genes, including alternatively spliced transcripts.
• The database aids in prioritizing candidate genes within mapped retinal disease regions.