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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Hayesmoore, Jesse B.G.
Languages: English
Types: Doctoral thesis
Subjects:
In recent years, molecular genetics research has identified a large number of putative susceptibility genes for a variety of complex psychiatric and neurodegenerative disorders. However, in most instances, the particular functional variants involved have not been identified, and it is typically unclear by what mechanism the pathogenic effect is mediated. Where a genetic association does not appear to be fully explicable by variants that alter the amino acid sequence of a protein, it is a reasonable hypothesis that the association might be mediated by cis-acting variants that alter gene expression. This hypothesis was tested in this thesis in relation to 10 putative susceptibility genes for psychiatric and neurodegenerative disorders. The genes were DISCI, RELN, GABRA4, GABRA5, GABRB1, GABRB2, GABRG2, GABRG3, NOS1AP and MAPT. Each one of these genes was investigated by assays of relative allelic expression applied to a large number of post mortem human brain samples. Samples were also genotyped for relevant variants that had previously shown association with disease in order to test those variants for a putative cis-regulatory effect. Cis-regulatory variation manifested as unequal expression of each parental gene copy at the mRNA level was detected in nearly all of the genes in at least one tissue sample. However, for only two genes (RELN and MAPT) was evidence obtained that specific variants implicated in disease influenced expression.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

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