Achondroplasia
In your research project, you will do an investigation of an assigned gene and protein associated with a human disease (Achondroplasia).
Imagine that you are a researcher who is interested in this gene, gene product and disease. Use all bioinformatics tools available online to gain better understanding of the problem. In your presentation and report: , ) Sj 1. Briefly describe the function of the gene and gene product as well as the phenotype (clinical picture). Start with using the OMIM database for better understanding of the condition, its genetic associations and molecular genetics.
2. Explain how mutations in the gene and protein could contribute to the observed phenotype. Explore the NCBI protein file. There may be more than one gene and protein associated with the disease. You need to look at those other genes/proteins as well. 3. Use various versions of the NCBI BLAST search to find similar sequences and probable homologues in humans and other species.
4. Find any corresponding entries in PDB. Present and discuss the protein structures associated with the condition. You can use NCBI VAST for protein structure alignments. How is it helpful in understanding gene’s function and in possible explaining of the pathology?
5. Use all appropriate online tools to complete the investigation and summarize your research. Have a conclusion briefly restating what you learned about the gene function and suggesting further research. Provide a list of references at the end of the report.
6. The focus of the project and presentation must be the bioinformatics aspects of the topic and your own investigation of the specific genes and proteins.
Sample Solution
Achondroplasia is a genetic condition affecting a protein in the body called the fibroblast growth factor receptor. In achondroplasia, this protein begins to function abnormally, slowing down the growth of bone in the cartilage of the growth plate. This leads to shorter bones, abnormally-shaped bones and shorter stature; adult height in people with achondroplasia is between 42 and 56 inches. In addition, 20 to 50 percent of children born with the condition will experience neurological impairment. Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. The phenotype is determined by a dominant allele that interferes with bone growth during development.