PowerPoint Presentation - Complex trait analysis, develop-ment, and genomics


	Ctbp2 should also be considered a high priority biological candidate gene responsible for modulating App expression levels. The C-terminal binding protein 2 is a transcriptional co-repressor also known as Ribeye. The gene produces two transcripts encoding distinct proteins. The short form is a transcriptional repressor that binds a Pro-X-Asp-Leu-Ser peptide motif and interacts with several transcription factors including EVI1, ZFPM1, and ZFHX1A (aka TCF8, deltaEF1). The longer isoform is a major component of specialized synapses in photoreceptors. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases.

	Notes:
	1. To find out more about CTBP2 protein and the Ctbp2 gene, link to iHOP at http://www.pdg.cnb.uam.es/UniPub/iHOP/ and type in CTBP2
	Try Arrowsmith at http://arrowsmith.psych.uic.edu/cgi-test/arrowsmith_uic/pubsmith.cgi
	2. Both APP and CTBP2 are involved in oxidoreducatase activity or Notch signaling. To establish this common gene ontology visit NCBI http://www.ncbi.nih.gov/entrez/query.fcgi?db=gene and enter each gene symbol.
	3. You can get interesting hints regarding Ctbp2 expression partners by examining the genetic correlations between Ctbp2 probe set 1422887_a_at and all other transcripts on the M430 Affymetrix array. Use the Striatum data set because we already know from previous work (the previous slide) that this gene is a cis QTL. You should be able to show that Ctbp2 and Notch3 have antagonistic expression patterns in striatum. The negative genetic correlation with E2f4 is even stronger. The transcript also has a high positive genetic correlation with Rdh14. Of particular interest with respect to APP protein processing, Ctbp2 covaries positively with Bace2 (the transcript of the beta site APP-cleaving enzyme 2).