Genomic Organization of TBK1 Copy Number Variations in Glaucoma Patients
| Autor: | Young H. Kwon, Robert Ritch, Alan L. Robin, Edwin M. Stone, Wallace L.M. Alward, Todd E. Scheetz, Adam P. DeLuca, John H. Fingert, Kazuhide Kawase, Jeffrey M. Liebmann |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine DNA Copy Number Variations DNA Mutational Analysis Interspersed repeat Alu element Protein Serine-Threonine Kinases Gene dosage Article 03 medical and health sciences 0302 clinical medicine Humans Medicine Low Tension Glaucoma Copy-number variation Intraocular Pressure Chromosome 12 Genomic organization Genetics business.industry Chromosome DNA Interspersed Repetitive Sequences Pedigree Ophthalmology 030104 developmental biology Mutation 030221 ophthalmology & optometry Female business |
| Zdroj: | Journal of Glaucoma. 26:1063-1067 |
| ISSN: | 1057-0829 |
| DOI: | 10.1097/ijg.0000000000000792 |
| Popis: | BACKGROUND Approximately 1% of normal tension glaucoma (NTG) cases are caused by TANK-binding kinase 1 (TBK1) gene duplications and triplications. However, the precise borders and orientation of these TBK1 gene copy number variations (CNVs) on chromosome 12 are unknown. METHODS We determined the exact borders of TBK1 CNVs and the orientation of duplicated or triplicated DNA segments in 5 NTG patients with different TBK1 mutations using whole-genome sequencing. RESULTS Tandemly duplicated chromosome segments spanning the TBK1 gene were detected in 4 NTG patients, each with unique borders. Four of 5 CNVs had borders located within interspersed repetitive DNA sequences (Alu and long interspersed nuclear element-L1 elements), suggesting that mismatched homologous recombinations likely generated these CNVs. A fifth NTG patient had a complex rearrangement including triplication of a chromosome segment spanning the TBK1 gene. CONCLUSIONS No specific mutation hotspots for TBK1 CNVs were detected, however, interspersed repetitive sequences (ie, Alu elements) were identified at the borders of TBK1 CNVs, which suggest that mismatch of these elements during meiosis may be the mechanism that generated TBK1 gene dosage mutations. |
| Databáze: | OpenAIRE |
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