Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA
| Autor: | Sheila A. Fisher, Andreas Janssen, Lars G. Fritsche, Thomas Loenhardt, Andrea Rivera, Bernhard H. F. Weber, Claudia N. Keilhauer |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Genotype genetic structures Polyadenylation RNA Stability DNA Mutational Analysis Molecular Sequence Data Biology Models Biological Polymorphism Single Nucleotide Linkage Disequilibrium Macular Degeneration chemistry.chemical_compound Gene Frequency Genetics medicine Humans Tissue Distribution Amino Acid Sequence RNA Messenger Indel Gene Aged Aged 80 and over Messenger RNA Base Sequence Serine Endopeptidases Proteins Retinal High-Temperature Requirement A Serine Peptidase 1 Macular degeneration medicine.disease eye diseases chemistry Case-Control Studies HTRA1 Maculopathy Female sense organs |
| Zdroj: | Nature Genetics. 40:892-896 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.170 |
| Popis: | Bernhard Weber and colleagues identify a previously unknown insertion-deletion polymorphism in ARMS2 (LOC387715), a gene associated with age-related macular degeneration. The variant leads to rapid mRNA turnover of the ARMS2 transcript, suggesting a role for this gene in AMD. Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of the central retina1,2,3. Genetic variants at two chromosomal loci, 1q31 and 10q26, confer major disease risks, together accounting for more than 50% of AMD pathology4,5,6,7,8,9. 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 findings12, 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. |
| Databáze: | OpenAIRE |
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