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Retinitis pigmentosa is a genetic disease that causes the breakdown and loss of retinal cells. Retinitis...

Retinitis pigmentosa is a genetic disease that causes the breakdown and loss of retinal cells. Retinitis pigmentosa often starts with decreased night vision and will progress to blindness as retinal cells die.

Several genes have been linked to Retinitis pigmentosa, one of which is GADD. Mice lacking GADD (these mice were experimentally created so that the GADD region of the genome was deleted) have increased expression of non-retinal genes in retinal cells. In other words, in these mutant mice, genes that are not normally expressed in the retina are expressed.  

Crx is a key retinal transcription factor. Crx binds regulatory elements called CBRs (Crx-binding regions). GADD has two CBRs, one immediately proximal to the transcription start site (TSS), and one a few hundred base pairs downstream of the TSS.

You have received DNA from three patients with Retinitis pigmentosa. From the DNA, you sequence the GADD gene and its proximal/core promoter region.   

None of the patients have mutations in the coding region of GADD. All of the mutations you find are in the CBRs. Your findings are below:

  • Patient 1 – Mutation in CBR1
  • Patient 2 – Mutation in CBR2
  • Patient 3 – Mutation in CBR1 and CBR2

Based on the phenotype of the mice lacking GADD, and what we’ve learned about gene expression what type of protein might GADD be? Explain your answer.

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Answer #1

Here, we learn about gene expression that expression of a gene is controlled by other genes called regulatory genes. Here, GADD is acting as regulatory gene for in expression of those genes which are not normally expressed. When GADD got deleted, its control on these genes was lost and hence, these genes started expressing. Hence, GADD is controlling the expression of these genes.

The protein formed by GADD is a suppressor protein because when GADD was expressed i.e. when GADD protein was being formed, the other genes (which are not expreesed normally)  were not expressed. It means GADD protien is supressing the expression of the gene which are not expressed normally.

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