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Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.
- Source :
-
PLoS genetics [PLoS Genet] 2010 Feb 05; Vol. 6 (2), pp. e1000836. Date of Electronic Publication: 2010 Feb 05. - Publication Year :
- 2010
-
Abstract
- A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Aged
Case-Control Studies
Chromosomes, Human, Pair 10 genetics
Cohort Studies
Enzyme Assays
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Haplotypes genetics
High-Temperature Requirement A Serine Peptidase 1
Humans
Luciferases metabolism
Male
Polymorphism, Single Nucleotide genetics
Proteins metabolism
Serine Endopeptidases metabolism
Utah
Macular Degeneration genetics
Proteins genetics
Serine Endopeptidases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 6
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 20140183
- Full Text :
- https://doi.org/10.1371/journal.pgen.1000836