Medical Genetics and Diagnostics

Human Genome Databases
The aim of this assignment is to become familiar with some of the main web sites that are associated with the human genome project. It will take the form of exploring some of the databases and analyzing a specific gene which may be associated with a human disease.
You will be allocated one gene from the list:
RSID Chr Position (B36) Genotype % Occurrence Gene
rs10988141 9 130686250 TT 8.99251 ABL1
Five activities will be carried out for the assignment:
1. Locate the chromosomal map position of the gene.
2. Obtain the exon / intron structure of the gene.
3. Investigate the rare homozygous SNPs for the patient.
4. Find the other single nucleotide polymorphisms (SNPs) within this gene.
5. Design PCR primers for the rare homozygous SNPs using a primer design program.
A valuable resource is:
OMIM (Online Mendelian Inheritance in Man)
This is a very good resource that provides background information on disease genes and extensive clinical information. It contains numerous links to the primary literature.
Specific information on the various activities:
1. Locate the chromosomal map position of your gene. What is the approximate size of the gene and list the nucleotide start and finish positions.
Use the following two genome browsers:
Several guides for the Ensembl website can be found on this link:
> see the tutorials listed under ?Using the Ensembl genome browser?
Click on left-hand column ?Genomes and Maps?, then click on the ?Map Viewer? in the Quick Links column on the right-hand side.
The ?Gene Gateway Workbook? can be found on this website a useful guide for the NCBI site.
2. Obtain the exon / intron structure of the gene.
Determine the number of exons and introns in the gene. Also provide a diagram showing the structural arrangement of exons and introns throughout the gene.
Use the same two genome browsers as in Question 1.
3. Investigate the rare homozygous SNPs for the patient
Access the NCBI and Ensembl websites and identify the rare homozygous SNPs that were
provided for your gene (patient data).
Which area of the gene are the SNPs located? (exon, intron, etc).
Do they change the coding region? What potential effect, in any, do the SNPs have on the final protein?
Variant Effect Predictor
4. Find the single nucleotide polymorphisms (SNP) within this gene.
Provide a summary of the SNPs for the gene. Determine how many SNPs are in the exons and introns. Are there any exons which have a greater proportion of SNPs, or are they randomly distributed?
Use the NCBI and Ensembl websites, as in question 3.
5. Design PCR primers for the gene using a primer design program
You will need to download the DNA sequence surrounding your rare homozygous SNPs for your gene and save it as a file (see question 3). Undergraduate students have one rare SNP, postgraduate students should use the two SNPs that were allocated. Approximately 300 bases either side of the SNP will be sufficient (~ 600 bases in total).
You should design PCR primers to the rare homozygous SNPs using a PCR primer design program.
The program is ?Primer3? which has been developed by the Whitehead Institute for Biomedical Research (Boston). Go to the following website;
Copy and paste the DNA sequence into the main box; examine the options and pick the primers. Repeat with the second rare homozygous SNP from the gene
Assignment details
The assignment should contain the following sections:
1. Background: it should include no more than one page on the particular gene and any
associated disease (using information from the listed websites, which should be referenced).
2. Results and Discussion: answers to the 5 questions. This part should also include a description of the process that you followed to arrive at the answers. Also include a discussion on which database or web resources were most useful for each part of the exercise.
3. References: list the web references used for the report. Use the Vancouver reference system with numbering throughout the report.
Take note of the following:
The main body of the report should be no longer than 5 to 6 pages. Additional diagrams or outputs from websites can be added as appendices. Please note: These appendices should be no more than 3 to 4 additional pages.