We Select a clinical problem with a genetic component (i.e. Insulin Dependent Diabetes Mellitus Type I and HLA-DQ) in our area of interest. We can pick an existing paradigm or be creative and speculative. Just pick a gene or loci that has clinical impact for either diagnostic or prognostic reasons. infectious diseases and most molecular targets are acceptable.Here are web sites that might help:
http://www.ncbi.nlm.nih.gov/ or http://gdbwww.gdb.org/gdb/
we need to prepare a report on this focal problem that includes the following:
1) Clinical background. The clinical impact in terms of disease processes, current conventional laboratory methodologies used and the need for genetic testing (i.e. what is the appropriate use of the test in the clinical setting). Two to three paragraphs should be sufficient.
2) Genetic code. A print out of the nucleic acid sequence including polymorphic sites. Whatever it takes. It is assumed that if the region of interest is only 300bp you don't provide 64000bp, but if it takes 3400bp to support your test, go for it. Annotate with where primers, enzyme cutting sites, probes, etc. are located on the sequence.
3) Generate two testing protocols. Include all reagents, the concentrations they are used at and their source. Real reagents here, no imaginary enzymes. Include controls and a diagram of expected results, be inclusive of all possible phenotypes stated in 2. Two pages maximum. One of the protocols can be a published, existing method. Alter it to make the second one.
4) Design two circulars/flyers focused on the gene, disease or organism you have selected.
a)The first flyer is to be designed as an announcement and educational tool for your new molecular assay. These should be focused on the needs of the clinical staff (read physician). Algorithms showing appropriate clinical utility would be helpful as well as discussion of the clinical relevance of the test. Convince the clinical world they should order your molecular test
over previous testing modalities or demonstrate how it adds that supportive piece to clinical picture. One 8.5" x 11" sheet of paper used any way you want, it can be a memo, a tri-fold brochure, printed on one side or both. This is to be used as a reference educational tool.
(b)The second flyer is for the individual who is being tested. This is to inform them of what you are testing, why your testing it and what the interpretation means. Remember, these are lay people you are educating and many fear and distrust science. This is only a 4" x 6" index card size.
I will explain the genetic disorder called Sickle Cell Anemia (SCA). Among the blood disorders in the American subcontinent, SCA is the most common one; although most prevalent in the African Americans. One in every 500 African Americans is affected by this disorder.
1) Cause of SCA: It is caused by a point mutation in the hemoglobin beta gene (HBB) found on chromosome 11p15.5. It is a recessive disease. Due to the mutation in the HBB gene, the structure of hemoglobin (Hb) is abnormal and is called HbS. Normal hemologin is made up of 4 chains; 2 alpha and 2 beta chains. The point mutation causes the amino acid glutamic acid to be translated to Valine in the beta chains of HbA, making it HbS. Hemoglobin is a protein that carries oxygen and imparts the red blood cells their peculiar color. Normal red blood cells are smooth, round and soft, which enables them to move easily through the blood vessels to carry oxygen to all parts of the body. In sickle cell disease, the abnormal hemoglobin S causes the red blood cells to become hard, pointed and sticky and shaped like crescents or sickles. This occurs under conditions of deoxygenation (low oxygen), individuals who are homozygous HbS, causes the red blood cells to distort their shape into stiff sickle shape cells. The sickle cells cluster together and due to their rigidity they block the small blood vessels producing microvascular occlusions and cause pain and eventually damaging the organs. Early in life, SCA causes chronic hemolytic anemia and severe infections especially with encapsulated bacteria and lots of pain.
Sickle cells also break up easily and survive for only 10 to 20 days compared to 120 days for normal red blood cells; this destruction causes anemia (which is shortage of red blood cells and hemoglobin).
Several tests are there to determine the type of hemoglobin, which include are Hemoglobin electrophoresis, Isoelectric focusing and Chromatography. These tests determine whether a person has a type of sickle cell disease or has the sickle cell trait. Genetic testing which includes analysis of DNA sequence is used to determine changes in the genes for making hemoglobin. This test indirectly predicts the type of hemoglobin made in the red cells.
2) Gene Symbol: ...
Clinical background to sickle cell anemia is modeled.