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HS Pawar, D Vaduva, T Darga, M Othman, CA Downs, T Guckian, G Skuta, S Sullivan, JE Richards; Nanophthalmos (NNO1) Candidate Gene Screening . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3397.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To prioritize candidate genes and screen them for mutations from the NNO1 gene critical region. Methods: Human genome project data was used to analyze the DNA sequence between the markers D114191 and D11S1883. The mRNAs from this region were analyzed using BLAST program for checking their identity. Links from www.ncbi.nlm.nih.gov and other databases were used to find the known or possible functions of the genes or the presence of conserved domains. Two affected and two unaffected individuals from our NNO1 pedigree were screened for mutations in each candidate gene by using ABI377 sequencing technology. Results: We have previously localized the NNO1 gene to a 14.7 cM interval between D11S905 and D11S987 on chromosome 11. Genotyping of additional members of the original NNO1 family identified recombination events that reduce the genetic interval for the NNO1 gene to about 5 Mb between D11S4191 and D11S1883. Consequently, we sought to prioritize the candidate genes and carry out mutation screening in our representative NNO1 family members. We identified more than 60 genes and mRNAs mapping to the NNO1 interval. We excluded the PAX6 gene by placing it outside of the NNO1 interval flanking markers. We have excluded, by direct DNA sequencing, at least 6 genes as causing the NNO1 defect. These include CHRM1 that is known to be involved in a chick model of form-deprived myopia, ROM1, VMD2, actin-binding protein encoded by LOC51035, MGC2574, and G-protein gene GNG3. Conclusion: More than 60 genes/mRNAs were identified in the NNO1 critical interval. The NNO1 defect is apparently not a defect in coding sequence or splice sites of PAX6, CHRM1, ROM1, VMD2, MGC2574, GNG3, or LOC51035. Additional candidate genes are being evaluated. Support: Grants from Midwest Eye Banks and Transplantation Center, and Research to Prevent Blindness.
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