So, we now realize that FAP is a result of a non-functional APC product, but how exactly does a protein become non-functional? The answer is simply mutations. Mutations are typically random changes to the nucleotides of a DNA sequence--in our case, the APC gene. There are many different types of mutations, but for simplicity, let's only consider mutations that change the overall shape of the final protein product in a way that is detrimental to the protein's proper functionality. In APC, mutations that occur in the promoter regions, the 5' CCAAT box, and a region known as the mutation cluster region (MCR) often result in non-functional protein products. It is thought that the number of devastating mutations in the APC gene correlates with the number of adenomatous polyps that develop in the colon, where more mutations result in greater numbers of polyps.
When a person gets his or her whole genome sequenced, all of that individual's SNPs (Single Nucleotide Polymorphisms, or single-base changes) are identified. These SNPs can be studied and compared to the reference human genome to determine whether or not the nucleotide change is detrimental to the protein product. After studying the SNPs of two great scientists, James Waston and J. Craig Venter, I was able to determine that neither of them are likely to have been diagnosed with FAP. The two men's genomes are both available for public viewing online and serve as a great resource for the beginnings of whole genome sequencing for the public.
Haplotypes and GWAS both involve identifying the interaction and inheritance of sets of genes that work together to produce a specific genotype/phenotype. Haplotype information and GWAS studying have not yet shed too much light on FAP, especially since the disease is believed to be attributed primarily to the function of a single gene (APC), rather than a set of genes.
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