You are interested in sequencing the gene for Tangier disease (OMIM 205404). The disorder is rare, so it is feasible to obtain only very few samples. The approximate chromosomal location of the gene is known

Question

How would you set about deciding on a model organism to use to study this disease, and what would you do once you had decided? (An outline of your procedure after the organism is chosen will be sufficient).

Answer 1

If the chromosomal location of the gene is known, you use homologous genes in a model organism to help you identify specific sequence information. For instance, if the gene you are interested in studying has a known homolog in mouse and Drosophila, you could choose one or both organisms and identify a conserved region of the gene. Using that sequence, you can design primers to help you sequence the human version of the gene. After identifying the human sequence, you can also use model organisms to help you identify residues necessary for proper protein function. Using site-directed mutagenesis, you can generate mutant versions of the protein and
look for changes in its function and phenotypes that resemble the human disorder in your model organism. This will ultimately give you an animal model for Tangier disease. Sometimes the mutation does not cause the same disorder or symptoms seen in humans, depending on your model organism, so it may also be necessary to screen your organism to determine if it is the best choice of animal to study the disease.