IBIOS 598B / BMMB 597 Genomics

IBIOS / BMMB 551 Genomics Assignment for Lessons 12 and 13 Finding function by phenotype and Genome Editing

There are four options, and you only have to do one. A report with about a page of text plus figures should be adequate.

Option 1. Genomics of Gene Regulation and Interpreting Phenotype- Associated SNPs

Genetic variants in a broad region around the MYC gene have been implicated in susceptibility to multiple cancers, and the large majority of these variants are in non-protein-coding regions. MYC is a proto-oncogene, and the hypothesis that some of these variants could affect the regulation of MYC has fueled many recent investigations. I have set up a browser session with many tracks of data similar to those discussed in this lesson opened in a 1 Mb region around MYC, hg19, chr8:128,115,001-129,115,000. Use the following hyperlink to connect to the session: http://genome.ucsc.edu/cgi-bin/hgTracks? hgS_doOtherUser=submit&hgS_otherUserName=rosshardison&hgS_otherUser SessionName=MYC_1Mb_Regulaton_GenomicsCourse

Your assignment for this option is to examine these tracks (obviously you can open more, change the settings, etc. as you wish) and discuss what they suggest to you about regulatory regions proximal and distal to MYC. You have two options for reporting on your insights: (a) You can turn in a report through Angel. (b) You can comment on a VoiceThread on the course content site. I’ve made a “presentation” with an image of the data tracks for this locus, and you can use the “comment” capacity in VoiceThread to give your comments verbally (note that there are “pencil” tools with which to draw on the image.

The tracks, from top to bottom, are : - Phenotype-associated genetic variants from the GWAS catalog (http://www.genome.gov/26525384). - Gene models, including noncoding RNA genes, from Gencode - Transcription factor occupancy - DNaseI hypersensitivity (chromatin accessibility) - Chromatin state segmentations based primarily on histone modifications (chromHMM) - Histone modifications

I tried to keep the data within the same cell types, but unfortunately, not all types of data are available for one cell type. Data from HeLa cells had the broadest coverage, but I had to go to some other cell lines for some types of data.

1 Option 2. For any trait that has been analyzed by genome-wide association studies, examine some of the loci harboring phenotype-associated variants with respect to epigenetic marks.

Use the GWAS Catalog as a source of phenotype-associated SNPs. Use ENCODE, Roadmap Epigenome, or the candidate Regulatory Element repository from ENCODE as sources of epigenetic data (or others if you know of some). In your report, explain how the epigenetic data inform you about potential roles for variants in this locus, and try to tie it into the phenotype of interest.

Here is the URL for accessing and visualizing the ENCODE candidate Regulatory Element repository, using the SCREEN visualizer: http://screen.umassmed.edu

Option 3. Discuss how genome editing could be used in the project you are developing for your semester project.

Option 4. Develop your own assignment that engages with the material.