Fritsche, Lars G. and Loenhardt, Thomas and Janssen, Andreas and Fisher, Sheila A. and Rivera, Andrea and Keilhauer, Claudia N. and Weber, Bernhard H. F. (2008) Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. NATURE GENETICS, 40 (7). pp. 892-896. ISSN 1061-4036, 1546-1718
Full text not available from this repository. (Request a copy)Abstract
Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of the central retina(1-3). Genetic variants at two chromosomal loci, 1q31 and 10q26, confer major disease risks, together accounting for more than 50% of AMD pathology(4-9). Signals at 10q26 center over two nearby genes, ARMS2 (age-related maculopathy susceptibility 2, also known as LOC387715)(8,9) and HTRA1 (high-temperature requirement factor A1)(10,11), suggesting two equally probable candidates. Here we show that a deletion-insertion polymorphism in ARMS2 (NM_001099667.1: c.*372_815del443ins54) is strongly associated with AMD, directly affecting the transcript by removing the polyadenylation signal and inserting a 54-bp element known to mediate rapid mRNA turnover. As a consequence, expression of ARMS2 in homozygous carriers of the indel variant is not detectable. Confirming previous findings(12), we demonstrate a mitochondrial association of the normal protein and further define its retinal localization to the ellipsoid region of the photoreceptors. Our data suggest that ARMS2 has a key role in AMD, possibly through mitochondria-related pathways.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPLEMENT FACTOR-H; X-LINKED RETINOSCHISIS; MACULOPATHY; HTRA1; SUSCEPTIBILITY; POLYMORPHISM; HAPLOTYPE; DISEASE; VARIANT; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 05:36 |
| Last Modified: | 29 Oct 2020 05:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30699 |
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