-- Overview -- This project will be looking at a genome from the Human Genome Project. The goal is to assess what kind of genetic variants the person could have that may lead to diseases. This was done by aligning, genotyping, and annotating a genome from the Human Genome Project.
-- Methods -- Aligning was first done in order to arrange the sequence to identify regions of similarity to the human reference genome. Then genotyping was done in order to find the genotypes at each particular site in the genome. The probable genotypes at each site can be found by looking at the nucleotides read at each site and considering the probability of seeing that nucleotide for each possible genotype. This process especially considers the SNPs and indels. The last step was annotation, which is used to add information on the variants, like which variants would be worth investigating further. Some variants may not be interesting, especially if they occur in the introns or if they are non- synonymous. The cases that occur in protein-coding regions where functional groups are important or the mutation creates a change in the amino acid would be worth investigating further. Annotation therefore adds biological information on top of our genetic data. The information added include genomic content (exonic/intronic), mutation type (synonymous/non-synonymous), RefGene ID, and metrics to see how harmful the mutation would be.
-- Results of Study -- A table of significant mutations are provided in the study. Three of the mutations that were mentioned as significant were the Chromosome 7 NOS3 gene mutation from T to G, which had implications on Heart Disease, the Chromosome 5 gene FGFR4 mutation from G to A, which had a significance on cancer progression and tumor cell motility, and the Chromosome 16 gene IL4R mutation from A to G, which was associated with a pathogenic change of susceptibility to atropy, and slow progression to acquired immuno-deficiency syndrome.
-- Focus on Chromosome 7 NOS3 gene mutation from T to G -- The rest of the study focused on this mutation. This non-synonymous SNV was associated with susceptibility to coronary artery spasm, late-onset Alzheimer disease, pregnancy-induced hypertension, hypertension resistant to conventional therapy, ischemic heart disease, and ischemic stroke. It was located in the exomic part of the genome, and was a pathogenic change. The NOS3 gene is a protein-coding gene and variations in the gene are associated with susceptibility to coronary spasm. Diseases that are associated with this gene include stroke, ischemic, and Alzheimer disease. The pathways involved are the Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics, and eNOS activation and regulation. In patients with coronary spasm, the incidence of the allele was significantly greater than in the control group, where regression analysis showed that the most predictive independent risk factor for coronary spasm was this mutant allele. On Chromosome 7 at position 150999023 we identified a non-synonymous SNV that was associated with susceptibility to coronary artery spasm, late-onset Alzheimer disease, pregnancy-induced hypertension, hypertension resistant to conventional therapy, ischemic heart disease, and ischemic stroke. This change from T to G was located in the exomic part of the genome. It was in the NOS3 gene and it was a pathogenic change. The NOS3 gene is a protein-coding gene and variations in the gene are associated with susceptibility to coronary spasm. Diseases that are associated with this gene include stroke, ischemic, and Alzheimer disease. The pathways involved are the Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics, and eNOS activation and regulation. In patients with coronary spasm, the incidence of the allele was significantly greater than in the control group, where regression analysis showed that the most predictive independent risk factor for coronary spasm was this mutant allele. The RS ID associated with this mutation is rs1799983. According to the 1000Genome study, this variant has high allele frequencies in most populations, though the frequencies for Africa seem to be higher (0.93) than Europe (0.65).