Establishing novel relationships between genetic variants and gene expression in humans

Abstract

We observe phenotypic variations in the human population every day; however, the underlying genetic mechanism behind these variations is difficult to decipher. In this project I investigate the links between phenotypic and genetic variations in humans via three different studies. First, I focus on the impact of the loss-of-function (LoF) mutations on the gene expression. To study the impact of LoF mutations on gene expression, messenger RNA (mRNA) sequences were aligned generating a map of similarities and differences in the RNA seq around the LoF mutation being analyzed. The patterns of RNA seq alignment were studied using the Integrative Genomics Viewer and compared with the list of LoF mutations. The results from the study of LoF mutations confirmed the presence of mutations which impact the gene expression for a particular disease and also reinstated the RNA-seq data obtained. Therefore, the genetic variants present did not necessarily cause the disease in all cases and the gene was not expressed when LoF mutations were present. This RNA editing mechanism protects individuals from the expression of the LoF mutations. Second, I focus on the expression level of mitochondrial DNA (mtDNA)-encoded genes. FPKM (fragments per kilobase of exon per million fragments) was used in the study of mtDNA-encoded genes to measure the relative abundance of transcripts in the RNA seq data. The study of mtDNA-encoded genes showed the presence of individual variations in the expression levels of the mtDNA and nuclear DNA encoded genes. I also found that the expression of nuclear genes is correlated to the expression of mtDNA-encoded genes.