Comparative analysis of aryl-hydrocarbon receptor interacting protein-like 1 (Aipl1), a gene associated with inherited retinal disease in humans

Abstract.

Mutations in AIPL1 cause Leber congenital amaurosis (LCA), the most severe form of inherited blindness in children; however, the function of this protein in normal vision remains unknown. To determine amino acid subsequences likely to be important for function, we have compared the protein sequence of several species. Sequence conservation is highest across the three Aipl1 tetratricopeptide (TPR) motifs and extends across the protein, except for a proline-rich amino acid sequence present only at the C-terminus of primate Aipl1. The length of the proline-rich region varies within primates; however, the length differences between human and primate Aipl1 do not correlate with evolutionary distance. These observations reinforce the importance of the TPR domains for function, the similarity of Aipl1 to a family of proteins that act as molecular chaperones, and the importance of comparative sequencing data for determination of whether AIPL1 sequence variants in patients are likely to cause retinopathy.