Your goal is to find and research the gene(s) that are responsible for genetic diseases in humans; these genes when mutated would include both the direct causes of the disease phenotype as well as any mutated genes that might increase suspectibility or risk for that disease. This site is mainly for your end-of-semester projects (the web-page project, done with Dreamweaver or other suitable software)...

For your presentation, you should become "mini-experts" in your disease; you should know and document (by keeping a bibliography) everything about your disease from its first discovery as a recognizable syndrome, through its inheritance pattern (pedigree analysis), to its localization on a chromosome, and finally to the usually extraordinary task of cloning and sequencing the mutated gene(s) responsible for the syndrome. Lastly, you should describe the molecular genetic basis of the disease in as much detail as is now known, and the correlation between specific mutations and the loss or gain of functions (or both) in the expressed gene(s).

We will discuss a few genetic diseases in class, and so clearly demonstrate the Candidate Gene and Positional Cloning strategies that have become so successful in isolating the relevant genes for human diseases, especially now that the human genome's sequence is known. We will also discuss GWAS, SNPs, the HapMap Project, ENCODE and how these approaches have changed the ways in which researchers find, identify, and characterize the mutated genes responsible for human diseases. Through such lecture discussions, you will see the kind of analyses you should perform for your paper and presentation.

In summary, address the following points in your report:

1. Initial discovery and Clinical aspects:
(a) Who first diagnosed and described the disease, and when was the disease first recognized as a characteristic syndrome?
(b) What are its symptoms, and how has it been treated?
(c) Who is at risk, i.e., what are the frequencies of occurrence among population sub-groups.
(d) Is onset or progession of the disease correlated in an age and/or developmental manner?
(e) What are the OMIM numbers and MIM codes for all the genes you have found to be responsible for or associated with the disease phenotype (and see steps 3 and 4)?

2. Mode of inheritance for the disease:
(a) Describe a typical pedigree in which the disease has been observed.
(b) How was the confirmed inheritance mode useful in finding the responsible gene in the genome?
(c) Was the pedigree data unequivocal?

3. Finding the gene's location:
(a) Which linkage studies have localized the disease gene to which chromosome?
(b) Describe and analyze these linkage studies.
(c) Were any chromosomal translocations or other structural abnormalities involved in localizing the mutated gene?
(d) Were somatic cell hybrids used in any of these studies?

4. GWAS Projects:
(a) Have any significant susceptibility factors been revealed for the disease?
(b) If so, how many relevant genes have been implicated or proven to be associated with or responsible for the disease phenotype?
(c) Cite the associated and/or responsible genes along with estimated risk assessments.
(d) Briefly describe the genes and what they encode or regulate, and how they might fit into a network of interactions (and see steps 6 and 7 where you will do a more detailed analysis of selected genes).
(e) List at least one significant SNP associated with the major mutated or associated gene(s) for the disease.

5. The Molecular/cloning Work:
(a) Describe and summarize the cloning work leading to the actual discovery of the gene(s), i.e., what happened after the gene was located to a chromosome, then a region in the chromosome, then associated with a DNA marker, then perhaps a haplotype block.
(b) Which experiments and methods were instrumental in generating the critical data which led to its discovery?
(c) How has the gene been characterized at the molecular level so far?
(d) Which type of mutations are involved (and see step 7-b)?
(e) Are there any peculiar features associated with this disease gene?

6. Perform the 'Gene Analysis Algorithm' (the one you did in class as part of the MuPAs) on at least one of the major or more important genes implicated as being responsible for or strongly associated with your disease. Enter the results or data from this exercise into a concise Table suitable for a Web document (and now see the next step #7 for some overlapping information). Similarly, enter the results of your Phylogenetic Tree analysis from the KEGG site into a form suitable for a Web document.

7. Mollecular/biochemical properties and Characteristics of the protein encoded by the disease gene.
(a) What is its size, how many amino acids are present in the normal protein, does it have any consensus structural motifs?
(b) Specifically, what amino acids are changed by what mutations to produce an abnormal protein product causing the disease symptoms?

8. Cite and explain any new diagnostic procedures based on the molecular information obtained from cloning and sequencing the gene, and learning about its protein product.

All presentations will be from your completed Web Site (use Dreamweaver or Power Point), by way of a projection system. The computer will be connected to our LAN, so that you will be able to present your project directly from your I:/drive folder, or other sources.