Study of genomic variability in the genetic susceptibility to psychiatric disorders: SNPs, CNVs and miRNAs
In this thesis we have studied genetic elements potentially contributing to the pathophysiology of psychiatric disorders, focusing on different sources of human genome variability, including SNPs and CNVs, which can affect not only coding genes but also RNA regulatory elements, such as miRNAs. First...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2010 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/7221 |
| Online Access: | http://www.tdx.cat/TDX-0207111-142731 http://hdl.handle.net/10803/7221 |
| Access Level: | Open access |
| Keyword: | gens candidats ritmes circadians trastorns afectius trastorns psiquiàtrics susceptibilitat genètica variabilitat genòmica candidate genes SNPs CNVs microRNAs circadian rhythms genetic susceptibility psychiatric disorders mood disorders genomic variability 575 |
| Summary: | In this thesis we have studied genetic elements potentially contributing to the pathophysiology of psychiatric disorders, focusing on different sources of human genome variability, including SNPs and CNVs, which can affect not only coding genes but also RNA regulatory elements, such as miRNAs. First, we have interrogated different candidate genes for psychiatric disorders overlapping with known CNVs, finding 14 different genes variable in copy number in psychiatric disorders but not in control individuals. Then, narrowing the analysis on mood disorders, we explored GSK3β gene considering both SNPs and a partially overlapping CNV. The GSK3β promoter and intron 1 region was found significantly associated with an earlier onset of the major depressive disorder. Finally, we have found evidence possibly pointing to a precise post-transcriptional regulation of circadian rhythms by miRNAs in mood disorder patients. Concretely, a variant in the precursor form of miR-182 could play an important role in fine-tuning its target sites involved in the control of sleep/wake cycles. Overall, we have provided evidence of different types of genome variation on neuronal genes or miRNA regulatory regions that can potentially contribute to the development of psychiatric disorders. |
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