Exercises:
Sample User Questions and Answers

	Hands-on exercises are interspersed within each module to reinforce the concepts/resources covered. They generally reflect questions frequently asked by end-users. This page pulls together all the exercises from the complete course for easy access. In many cases, there are several ways to arrive at an answer. Each exercise generally demonstrates one strategy as an example.

InfoHubs Similarity Searching Human Genome Non-Human Genomes Clinical Resources Variation Resources Expression Resources Structures Additional Analytical Tools DNA Analysis RNA Resources Protein Analysis Phylogenetic Resources Special Purpose Resources Outreach and Communication

INFORMATION HUBS

	Find concise summary of sequence records for gene of interest    [how to hone a search]	strategy

	Restrict nucleotide search results to a specific molecule type    [Entrez Limits]	strategy

	Retrieve only sequences from patents    [Entrez Details function, Index function, Properties Field]	strategy

	Retrieve sequence records that were added or modified between two dates.    [range searching]	strategy

	Retrieve records annotated with a given biological feature (e.g., promoter)    [Feature Key field]	strategy

	Find official gene symbol and alternative symbols for given gene    [Entrez Gene]	strategy

	Find loci involved in a given biological process (e.g., DNA mismatch repair)    [Entrez Gene]	strategy

	Find loci associated with phenotypes but no corresponding sequence data    [Entrez Gene]	strategy

	List and status of genome projects (e.g., microbial genomes)    [Entrez Genome Project]	strategy

	Retrieve all data from a given organism or taxon    [Taxonomy Browser]	strategy

	Viral isolates: for a given virus, determine which isolates are represented in the sequence databases.    [Taxonomy Browser]	strategy

	Find restriction map software    [directories of molbio databases and software]	strategy

	What resources can be used to identify potential transcription factor binding sites in a DNA sequence?    [directories of molbio databases and software]	strategy

SIMILARITY SEARCHING

	Use BLAST 2 Sequences to look for mismatches between two protein sequences.	strategy

	How to determine if a match to a sequence region is significant?	strategy

	How can I find if my bacterial protein has significant similarity to any metazoan proteins?	strategy

	What regions of my protein have significant similarity to functional domains?	strategy

HUMAN GENOME

	Find the chromosomal location of a gene	strategy

	Manipulating the MapViewer: customizing the view of a chromosome region	strategy

	Choosing Maps: identifying the maps that have objects (ESTs, STSs, SNPs, disease genes, etc.) relevant to your needs	strategy

	Using e-PCR: identifying STSs near or within a gene locus of interest	strategy

	Using Model Maker: display alternate views of a gene model and download corresponding sequence data	strategy

	Using HomoloGene: identify homologs for a gene of interest	strategy

	Where is a gene located? Find flanking markers and SNPs.	strategy

	What genes are found in a specific cytogenic location? Display them in a tabular format.	strategy

	View a gene at the sequence level. Identify exons and introns.	strategy

	Download the sequence data between two markers.	strategy

	Find the genomic DNA clone that corresponds to a specific mRNA.	strategy

	Find and download the 500bps of genomic sequence upstream of a gene.	strategy

	Compare human and mouse versions of a gene. Display human and mouse maps simultaneously in the MapViewer.	strategy

N0N-HUMAN GENOMES

	Using the ORF Finder to find a gene in a prokaryotic DNA sequence	strategy

	Identifying a gene in a eukaryotic DNA sequence via computation	strategy

	Locating and accessing complete microbial genomes	strategy

	Eukaryotic genes in prokaryotic genomes	strategy

	Retrieve the sequence for a specific gene from a prokaryotic genome	strategy

	Gene function in a genome: get a list of proteins involved in specific funcational groups	strategy

	Find a eukaryotic homolog of a prokaryotic gene (e.g., mutL homolog in the Drosophila genome)	strategy

	Find a model organism for studying Huntingtons Disease	strategy

	Are RAG1 and RAG2 examples of Horizontal Gene Transfer (HGT) from a prokaryote into a eukayote?	strategy

CLINICAL RESOURCES

	Investigating treatment options for a genetic disease (e.g., Gaucher)	strategy

	Familial Cancers (e.g., medullary thyroid cancer)	strategy

	Inherited diseases: finding general information / gene identification / chromosomal location (e.g., obesity)	strategy

	Staying current: genetic diseases and research progress (e.g., retinoblastoma)	strategy

	Locating disease genes on a specific chromosome (e.g., cancer genes on chrom. 12)	strategy

	How many genes are involved in a disease? (e.g., alveolar cell carcinoma)	strategy

	Clinically relevant information in OMIM (e.g., cystic fibrosis)	strategy

	Mode of inheritance (e.g., papillary thyroid carcinoma)	strategy

	Genetic risk factors (e.g., Tay-Sachs disease)	strategy

	Genetic testing (e.g., Huntington's Disease)	strategy

	Patient counseling and education (e.g., Duchenne's Muscular Dystrophy (DMD))	strategy

	Treating genetic diseases (e.g., inherited mitochondrial respiratory chain diseases)	strategy

	Public health incorporates genomics (e.g., CDC Genetics and Genomics)	strategy

	Disease prevalence (e.g., prostate cancer in U.S. vs. western Europe)	strategy

	Population screening (e.g., osteoporosis)	strategy

	Orphan drugs (e.g., sickle cell anemia)	strategy

VARIATION RESOURCES

	Find SNPs in a gene	strategy

	Genome-oriented SNP visualization	strategy

	How to create a genetic variation map	strategy

	Functional analysis of a SNP	strategy

	Identify disease-causing mutations	strategy

	Analysis of exonic SNPs	strategy

	Find SNPs in a given base pair range on an assembled genome	strategy

EXPRESSION RESOURCES

	Identifying tissue specific RNA markers	strategy

	Normalization of expression data against "housekeeping" genes	strategy

	Sample size and confidence in expression data	strategy

	Discrepancies in gene expression pattern data: How to interpret?	strategy

	Discrepancies in gene expression pattern data: Sample preparation	strategy

STRUCTURES

	View a structure with Cn3D (wild-type HIV reverse transcriptase)	strategy

	Manipulate structure with Cn3D - zoom, rotate, change rendering and coloring styles, show/hide, annotate, add labels, remove chain from view (wild-type HIV reverse transcriptase)	strategy

	Manipulate NMR structure with Cn3D - use animation to view different NMR models (calmodulin)	strategy

	View sequence to structure aligment, via BLINK. Align a protein sequence without a known structure (e.g., human Apolipoprotein A4, "ApoA IV") to a sequence that does have a resolved structure, then use Cn3D to display an alignment of the two.	strategy

	View sequence to structure aligment, via Cn3D Import Window (human Apolipoprotein A4, "ApoA IV"). Similar problem to the one above, using a different approach to retrieve and view the structures.	strategy

	View the 3-dimensional structure of a conserved domain and its sequence alignments in Cn3D (ARF (ADP-ribosylation factor) conserved domain)	strategy

	View alignment of two proteins that have similar 3-D structures. Use VAST structure neighbors to identify proteins that are similar based on 3-D structure (e.g., Drosophila calmodulin aligned to turkey troponin-C), and view the aligned structures in Cn3D.	strategy

	View a structure alignment, via Cn3D Import Window. Align multiple proteins that are similar based on 3-D structure (human Leptin protein aligned to human Ciliary Neurotrophic Factor protein, then import the structure for human prolactin).	strategy

	View a structure with Rasmol (e.g., hexokinase 1). Compare to the same structure in Cn3D.	strategy

	Align the structures of the wild type and mutated forms of a protein, and locate the position of the mutation (B-chains of Sickle Cell and Wildtype Hemoglobin)	strategy

	Protein Conformation: compare two forms of the same protein under different conditions	strategy

	Ligand Binding: compare structure of free protein vs. bound protein	strategy

	DNA binding: view zinc-finger DNA binding domain of a protein (Gata-1) bound to its DNA substrate	strategy

DNA ANALYSIS

	Restriction mapping	slides

	PCR primer design	slides

	Multiple sequence alignments	slides

	Translate DNA/RNA to protein	slide

	Finding promoters	slide

RNA RESOURCES

	Retrieve sequence records for various RNA molecule types	strategy

	Find known RNAi reagents for a specific gene	strategy

	Retrieve modification information for RNAs	strategy

	Predict a 2D structure for an RNA sequence	strategy

	Determine base pairing interactions from structure files	strategy

PROTEIN ANALYSIS

	The August 2-6, 2004 course is based on the NCBI Mini-Course, "Making Sense of DNA and Protein Sequences", by Medha Bhagwat and David Wheeler. All of the "strategy" links below point to the electronic notebook for that course, which is a single page that covers the following topics:

Find a gene within a eukaryotic DNA sequence and generate a protein translation using GenScan

strategy

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