GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism
| Autor: | Jie Zheng, Uma Dandekar, Alejandra Young, C. Avery Sader, Calvin Pan, Richard A. Lewis, Debora B. Farber |
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| Přispěvatelé: | Lewin, Alfred S |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Candidate gene lcsh:Medicine GTP-Binding Protein alpha Subunits Gi-Go Biochemistry Gi-Go Exon Untranslated Regions Models 2.1 Biological and endogenous factors Aetiology lcsh:Science 3' Untranslated Regions Base Pairing Genetics Sanger sequencing Multidisciplinary Messenger RNA Homozygote Genomics Single Nucleotide Exons Albinism Ocular GTP-Binding Protein alpha Subunits Nucleic acids Phenotypes 5' Utr Albinism symbols Ocular albinism type 1 Sequence Analysis Research Article Ocular albinism Heterozygote General Science & Technology Biology Genome Complexity Research and Analysis Methods Polymorphism Single Nucleotide Frameshift mutation 03 medical and health sciences symbols.namesake Sequence Motif Analysis Ocular medicine Humans Genetic Predisposition to Disease Polymorphism Molecular Biology Techniques Sequencing Techniques Gene Molecular Biology Eye Disease and Disorders of Vision Genetic Association Studies 030102 biochemistry & molecular biology Biology and life sciences Base Sequence lcsh:R Neurosciences Computational Biology Reproducibility of Results Molecular Sequence Analysis DNA DNA medicine.disease eye diseases Introns 030104 developmental biology Genetic Loci Mutation RNA lcsh:Q sense organs 5' Untranslated Regions Sequence Alignment |
| Zdroj: | Young, A; Dandekar, U; Pan, C; Sader, A; Zheng, JJ; Lewis, RA; et al.(2016). GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. PLOS ONE, 11(9). doi: 10.1371/journal.pone.0162273. UCLA: Retrieved from: http://www.escholarship.org/uc/item/9hd4r6w4 PloS one, vol 11, iss 9 PLoS ONE, Vol 11, Iss 9, p e0162273 (2016) PLoS ONE |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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