15. Genomes and Genomics

Which of the following is NOT a piece of information that bioinformatics can analyze?

Which of the following can be used to identify an open-reading frame?

Go to the National Institute for Child Health and Human Development (http://www.nichd.nih.gov), locate the search box at the top right corner of the homepage, and enter 'RUSP' to search for information on the Recommended Uniform Screening Panel. From the options that appear, select 'Brief History of Newborn Screening' and locate the discussion listing the criteria for adding a disease to the RUSP list. What are the criteria for listing a disease on the RUSP list?

What are community-based genetic screening programs? What is the intent of such screening programs? Why are members of specific communities or populations offered the chance to participate in such programs?

What is bioinformatics, and why is this discipline essential for studying genomes? Provide two examples of bioinformatics applications.

You are designing algorithms for the bioinformatic prediction of gene sequences. How might algorithms differ for predicting genes in bacterial versus eukaryotic genomic sequence?

Do you think it is important that participation in community-based genetic screening be entirely voluntary? Why or why not?

BLAST searches and related applications are essential for analyzing gene and protein sequences. Define BLAST, describe basic features of this bioinformatics tool, and give an example of information provided by a BLAST search.

Go to http://blast.ncbi.nlm.nih.gov/Blast.cgi and follow the links to nucleotide blast. Type in the sequence below; it is broken up into codons to make it easier to copy.

5' ATG TTC GTC AAT CAG CAC CTT TGT GGT TCT CAC CTC GTT GAA GCTTTG TAC CTT GTT TGC GGT GAA CGT GGT TTC TTC TAC ACT CCT AAG ACT TAA 3'

As you will note on the BLAST page, there are several options for tailoring your query to obtain the most relevant information. Some are related to which sequences to search in the database. For example, the search can be limited taxonomically (e.g., restricted to mammals) or by the type of sequences in the database (e.g., cDNA or genomic). For our search, we will use the broadest database, the 'Nucleotide collection (nr/nt).' This is the nonredundant (nr) database of all nucleotide data (nt) in GenBank and can be selected in the 'Database' dialogue box. Other parameters can also be adjusted to make the search more or less sensitive to mismatches or gaps. For our purposes, we will use the default setting, which is automatically presented. Press 'BLAST' to search. What can you say about the DNA sequence?

In the course of the Drosophila melanogaster genome project, the following genomic DNA sequences were obtained. Try to assemble the sequences into a single contig.

5' TTCCAGAACCGGCGAATGAAGCTGAAGAAG 3'
5' GAGCGGCAGATCAAGATCTGGTTCCAGAAC 3'
5' TGATCTGCCGCTCCGTCAGGCATAGCGCGT 3'
5' GGAGAATCGAGATGGCGCACGCGCTATGCC 3'
5' GGAGAATCGAGATGGCGCACGCGCTATGCC 3'
5' CCATCTCGATTCTCCGTCTGCGGGTCAGAT 3'

Go to the URL provided in Problem 14, and using the sequence you have just assembled, perform a blastn search in the 'Nucleotide collection (nr/nt)' database. Does the search produce sequences similar to your assembled sequence, and if so, what are they? Can you tell if your sequence is transcribed, and if it represents protein-coding sequence? Perform a tblastx search, first choosing the 'Nucleotide collection (nr/nt)' database and then limiting the search to human sequences by typing Homo sapiens in the organism box. Are homologous sequences found in the human genome? Annotate the assembled sequence.