Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download A functional polymorphism in miRNA
Document related concepts
Pathogenomics wikipedia , lookup
Population genetics wikipedia , lookup
Genetic engineering wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Long non-coding RNA wikipedia , lookup
RNA interference wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Heritability of IQ wikipedia , lookup
History of genetic engineering wikipedia , lookup
Minimal genome wikipedia , lookup
Gene expression programming wikipedia , lookup
Genomic imprinting wikipedia , lookup
Human genetic variation wikipedia , lookup
Genome evolution wikipedia , lookup
Neuronal ceroid lipofuscinosis wikipedia , lookup
Ridge (biology) wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Behavioural genetics wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Fetal origins hypothesis wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Medical genetics wikipedia , lookup
Gene expression profiling wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Genome (book) wikipedia , lookup
Transcript
A functional polymorphism in miRNA-1229 influences the risk of Alzheimer’s disease Mohsen Ghanbari1,2, M. Arfan Ikram1 , Hans W.J. de Looper3, Albert Hofman1, Stefan J. Erkeland3, Oscar H. Franco1, Abbas Dehghan1. 1. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. 2. Department of Genetics, School of medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Department of Hematology, Erasmus University Medical Center, Cancer Institute, Rotterdam, the Netherlands. Genome-wide association studies (GWAS) have enabled us to identify a large number of genetic variants associated with Alzheimer’s disease (AD). However, the vast majority of the identified variants are non-genic that their biological relevance to the disease remain to be elucidated. MicroRNAs (miRNAs) serve as key post-transcriptional regulators of gene expression and are involved in various biological processes. Genetic variation in miRNArelated sequences has been shown to interfere with miRNA gene regulation and subsequently affect disease risk. Here, we investigated the extent to which variants fall in miRNAs and miRNA-binding sites could constitute a part of the functional variants associated with AD. Using data from the thus far largest GWAS on late-onset AD, we found that rs2291418 (Chr5;179798324:G>A) within the pre-miR-1229 sequence is associated with an increased risk of AD (p-value=6.8×10-5 and β=0.18). In silico analysis showed that rs2291418 affect the processing of pre-miR-1229 and in vitro assays demonstrated that the mutant allele enhance the level of mature miR-1229-3p. Subsequently, we found a number of miR-1229-3p target genes that may mediate the miRNA-effect on AD. Furthermore, we identified 11 variants in the 3’UTR of 10 genes linked with AD that would potentially interfere with miRNAmediated regulation of the host genes by disrupting, creating or modifying miRNA binding sites. With this approach, we further found two new genes, DMWD and HBEGF, that are associated with AD. These findings may improve our understanding of the role of miRNAs in the pathophysiology of AD and contribute to better annotation of GWAS findings.
