Retinitis pigmentosa is a genetic disease that causes thebreakdown and loss of retinal cells. Retinitis pigmentosa oftenstarts with decreased night vision and will progress to blindnessas retinal cells die.
Several genes have been linked to Retinitis pigmentosa, one ofwhich is GADD. Mice lacking GADD (these mice were experimentallycreated so that the GADD region of the genome was deleted) haveincreased expression of non-retinal genes in retinal cells. Inother words, in these mutant mice, genes that are not normallyexpressed in the retina are expressed. Â
Crx is a key retinal transcription factor. Crx binds regulatoryelements called CBRs (Crx-binding regions). GADD has two CBRs, oneimmediately proximal to the transcription start site (TSS), and onea few hundred base pairs downstream of the TSS.
You have received DNA from three patients with Retinitispigmentosa. From the DNA, you sequence the GADD gene and itsproximal/core promoter region.  Â
None of the patients have mutations in the coding region ofGADD. All of the mutations you find are in the CBRs. Your findingsare below:
- Patient 1 – Mutation in CBR1
- Patient 2 – Mutation in CBR2
- Patient 3 – Mutation in CBR1 and CBR2
How can mutations in non-coding regions cause a changein phenotype (in this case leading to retinitispigmentosa)? Note: you do not have to give all possible reasons,explanations of one or two ways mutations in non-coding regions canhave phenotypic effects is sufficient.
