GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism.
Ocular albinism type 1 (OA), caused by mutations in the OA1 gene, encodes a G-protein coupled receptor, OA1, localized in melanosomal membranes of the retinal pigment epithelium (RPE). This disorder is characterized by both RPE macro-melanosomes and abnormal decussation of ganglion cell axons at the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5015898?pdf=render |
| _version_ | 1818922926393524224 |
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| author | Alejandra Young Uma Dandekar Calvin Pan Avery Sader Jie J Zheng Richard A Lewis Debora B Farber |
| author_facet | Alejandra Young Uma Dandekar Calvin Pan Avery Sader Jie J Zheng Richard A Lewis Debora B Farber |
| author_sort | Alejandra Young |
| collection | DOAJ |
| description | Ocular albinism type 1 (OA), caused by mutations in the OA1 gene, encodes a G-protein coupled receptor, OA1, localized in melanosomal membranes of the retinal pigment epithelium (RPE). This disorder is characterized by both RPE macro-melanosomes and abnormal decussation of ganglion cell axons at the brain's optic chiasm. We demonstrated previously that Oa1 specifically activates Gαi3, which also signals in the Oa1 transduction pathway that regulates melanosomal biogenesis. In this study, we screened the human Gαi3 gene, GNAI3, in DNA samples from 26 patients who had all clinical characteristics of OA but in whom a specific mutation in the OA1 gene had not been found, and in 6 normal control individuals. Using the Agilent HaloPlex Target Enrichment System and next-generation sequencing (NGS) on the Illumina MiSeq platform, we identified 518 variants after rigorous filtering. Many of these variants were corroborated by Sanger sequencing. Overall, 98.8% coverage of the GNAI3 gene was obtained by the HaloPlex amplicons. Of all variants, 6 non-synonymous and 3 synonymous were in exons, 41 in a non-coding exon embedded in the 3' untranslated region (UTR), 6 in the 5' UTR, and 462 in introns. These variants included novel SNVs, insertions, deletions, and a frameshift mutation. All were found in at least one patient but none in control samples. Using computational methods, we modeled the GNAI3 protein and its non-synonymous exonic mutations and determined that several of these may be the cause of disease in the patients studied. Thus, we have identified GNAI3 as a second gene possibly responsible for X-linked ocular albinism. |
| first_indexed | 2024-12-20T02:01:18Z |
| format | Article |
| id | doaj.art-6467a785dc48450a8ddbece4c801fcbf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:01:18Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6467a785dc48450a8ddbece4c801fcbf2022-12-21T19:57:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016227310.1371/journal.pone.0162273GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism.Alejandra YoungUma DandekarCalvin PanAvery SaderJie J ZhengRichard A LewisDebora B FarberOcular albinism type 1 (OA), caused by mutations in the OA1 gene, encodes a G-protein coupled receptor, OA1, localized in melanosomal membranes of the retinal pigment epithelium (RPE). This disorder is characterized by both RPE macro-melanosomes and abnormal decussation of ganglion cell axons at the brain's optic chiasm. We demonstrated previously that Oa1 specifically activates Gαi3, which also signals in the Oa1 transduction pathway that regulates melanosomal biogenesis. In this study, we screened the human Gαi3 gene, GNAI3, in DNA samples from 26 patients who had all clinical characteristics of OA but in whom a specific mutation in the OA1 gene had not been found, and in 6 normal control individuals. Using the Agilent HaloPlex Target Enrichment System and next-generation sequencing (NGS) on the Illumina MiSeq platform, we identified 518 variants after rigorous filtering. Many of these variants were corroborated by Sanger sequencing. Overall, 98.8% coverage of the GNAI3 gene was obtained by the HaloPlex amplicons. Of all variants, 6 non-synonymous and 3 synonymous were in exons, 41 in a non-coding exon embedded in the 3' untranslated region (UTR), 6 in the 5' UTR, and 462 in introns. These variants included novel SNVs, insertions, deletions, and a frameshift mutation. All were found in at least one patient but none in control samples. Using computational methods, we modeled the GNAI3 protein and its non-synonymous exonic mutations and determined that several of these may be the cause of disease in the patients studied. Thus, we have identified GNAI3 as a second gene possibly responsible for X-linked ocular albinism.http://europepmc.org/articles/PMC5015898?pdf=render |
| spellingShingle | Alejandra Young Uma Dandekar Calvin Pan Avery Sader Jie J Zheng Richard A Lewis Debora B Farber GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. PLoS ONE |
| title | GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. |
| title_full | GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. |
| title_fullStr | GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. |
| title_full_unstemmed | GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. |
| title_short | GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. |
| title_sort | gnai3 another candidate gene to screen in persons with ocular albinism |
| url | http://europepmc.org/articles/PMC5015898?pdf=render |
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