Comparative Genomics Practical Platelet-derived growth factor receptors (PDGFR) Platelet-derived growth factor (PDGF) is one of a variety of growth factors that regulate cell division and growth. In particular, PDGF plays a role in blood vessel formation or angiogenesis. The different isoforms of PDGF activate cellular response through receptors including PDGF receptor alpha (PDGFRa) and beta (PDGFRb). The goals of this practical are as follows: 1. Explore the genomic location of PDGF receptor alpha and beta. 2. Speculate on the evolutionary origins of these receptors. 3. Understand how the UCSC genome browser works. 1. Identifying PDGFR on the UCSC genome browser Search the UCSC genome browser (http://genome.ucsc.edu/cgi-bin/hgGateway) using the term “PDGFR”. The genome browser returns a list of genomic locations for genes that match your search query. Click on the link to RefSeq genes that correspond to PDGRF alpha and beta. Remember: you will need two browser open on your desk top so that you can compare the alpha and beta genes. 1a. PDGFR alpha maps to chromosome ________ 1b. PDGFR beta maps to chromosome _________ 2. Navigating the genome browser Use the zoom out buttons on the top right-hand corner to refresh the graphic display. Zooming out will display more genes in the same graphics window. 2.1 Downstream neighboring gene for PDGFR alpha = _____________ 2.2 Downstream neighboring gene for PDGFR beta =________________ 2.3 Do the PDGFR genes and their corresponding neighbors share any protein classification? 2.4 What implications, if any, do your answers above together with the genomic location of these genes have on the origins of the PDGFR genes? 3. Comparative Genomics Track Zoom out until you only have the PDGFR alpha gene in full view. Scroll down till you see the “comparative genomics” tracks. Set the “conservation” track to “full”. 3.1 Which 4 species do not show any conservation with human PDGFR-alpha from position 54800000 – 54810000. 3.2 Explain the following terms that are used to describe the level of detail on a “track”? 3.2.1 full 3.2.2. dense 3.2.3 squish 3.2.4 pack 3.3 Hide the “conservation” track and scroll to the “Expression and Regulation” section. Set the “TFBS_conserved” track to “full”. List the two TFBS that are located at the “most” three prime end of the PDGFR alpha gene. 4. ENSEMBL GENOME BROWSER (www.ensembl.org) Click on the human division of ensembl and search for PDGFR. 4.1 Identify the ENSEMBL ProteinID for PDGFR Beta. 4.2 Click on the ProteinID and find a summary report of the different domains for the protein. One of the tracks shows a “SMART domain”. What database does “SMART” refer too? 4.3 What specific domain(s) is/are reported from the SMART database.