- Learn how to describe and analyze human genomic data
- Identify homologs in model organism genomes for human genes
- Human gene and variant analysis in Drosophila
Human Gene Analysis (Week 1-2)
1. (Beginning at www.genenames.org)- What is the difference between approved names and approved symbols for genes? How many human genes belong to these gene families: Transient receptor potential cation channels, peroxins and T-boxes? What are the homologs for PEX1 in other organisms?
2. (Beginning at www.omim.org)- What types of entries are marked by “#”, “*” and “%” ? For the PEX1 gene *602136, how many gene-phenotype relationships are available? What type of information is shown in “Clinical synopsis” and “Phenotypic Series”? What type of genetic mechanism (gain of function, loss of function) and inheritance (dominant, recessive) is described in OMIM for PEX1, AHDC1, ACTG2, ACTA2, ANKLE2, MYH11.
3. UniProt- Familiarize yourself with the Function and domains
Human Variant Analysis (Week 3-4)
1. What is a "de novo" versus “novel” variant, what is a “pathogenic variant”? What are the considerations in determining variant causality ( Guidelines for Determining Variant Causality)?
2. How do we describe variants? http://varnomen.hgvs.org; examine variant tables in our ACTG2 paper (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004258)
3. (Beginning at http://genome.ucsc.edu) input variants from these variants (use hg19). Examine adding tracks in your browser including ExAC, dbSNP, DGV, DECIPHER, ENCODE, examine the different options (full, pack, dense, squish).
4. (Beginning at http://grch37.ensembl.org/Homo_sapiens/Tools/VEP)- annotate your variants.
5. Examine a variant of interest- look for it in ExAC (http://exac.broadinstitute.org) and GnomAD (http://gnomad.broadinstitute.org), Geno2MP (http://geno2mp.gs.washington.edu/Geno2MP/#/). You can combine searches using our tool MARRVEL (http://www.marrvel.org).
6. Learn to interpret gene-based scored PLI (ExAC), RVIS (http://genic-intolerance.org) and variant based scores SIFT, Polyphen-2.
Model Organisms (Weeks 5-6)
1. Define the terms ortholog, homolog and paralog
2. (Beginning at http://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl) Predict the ortholog in 3 model organisms for these human genes: PEX1, AHDC1, ACTA2, ACTG2, MYH11, DNM1L, DNM1, PEX16. Compare these outputs to those from HCOP (www.genenames.org).
3. Examine a few test variants in DIOPT, is your variant conserved in Drosophila?
4. Examine genes of interest in gene2function.org and in https://monarchinitiative.org.
5. Examine genes of interest in flybase. What alleles have phenotypes? What stocks are available?
Model Organism Screening (Weeks 7-8)
1. Discuss the intersection of model organism work and human genomics (Fruit Flies in Biomedical Research).
2. Discuss an analysis pipeline using Drosophila (Morgan's Legacy).
Final Presentation (Week 7-8)
Prepare a presentation on your rotation project