Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA.

@article{citeulike:2924193, abstract = {Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of the central retina. Genetic variants at two chromosomal loci, 1q31 and 10q26, confer major disease risks, together accounting for more than 50\% of AMD pathology. Signals at 10q26 center over two nearby genes, ARMS2 (age-related maculopathy susceptibility 2, also known as LOC387715) and HTRA1 (high-temperature requirement factor A1), 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, 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.}, address = {[1] Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. [2] These authors contributed equally to this work.}, author = {Fritsche, Lars G G. and Loenhardt, Thomas and Janssen, Andreas and Fisher, Sheila A A. and Rivera, Andrea and Keilhauer, Claudia N N. and Weber, Bernhard H F H. }, citeulike-article-id = {2924193}, doi = {http://dx.doi.org/10.1038/ng.170}, issn = {1546-1718}, journal = {Nature genetics}, keywords = {degeneration, htra1, macular, snp}, month = {May}, posted-at = {2008-06-24 20:23:59}, priority = {2}, title = {Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA.}, url = {http://dx.doi.org/10.1038/ng.170}, year = {2008} }

TY - JOUR ID - citeulike:2924193 L3 - citeulike-article-id:2924193 TI - Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. JF - Nature genetics AD - [1] Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. [2] These authors contributed equally to this work. SN - 1546-1718 N2 - Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of the central retina. Genetic variants at two chromosomal loci, 1q31 and 10q26, confer major disease risks, together accounting for more than 50% of AMD pathology. Signals at 10q26 center over two nearby genes, ARMS2 (age-related maculopathy susceptibility 2, also known as LOC387715) and HTRA1 (high-temperature requirement factor A1), 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, 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. KW - degeneration KW - htra1 KW - macular KW - snp AU - Fritsche, Lars G AU - Loenhardt, Thomas AU - Janssen, Andreas AU - Fisher, Sheila A AU - Rivera, Andrea AU - Keilhauer, Claudia N AU - Weber, Bernhard H F PY - 2008/05/30/ UR - http://dx.doi.org/10.1038/ng.170 ER -