Asthma and genetics: Investigating nucleotide variants

摘要

This project was carried out with the goal of identifying genes with the strongest evidence for a role in asthma. Background: Asthma is a very common disease resulting from a combination of genetic and environmental factors. Many genes have been shown to contribute to asthma risk, but the heterogeneity of the disease makes it difficult to know which genes contribute to specific phenotypes. Methods: This project was completed using publicly available genome-wide gene expression datasets. These sets were compared to find overlapping genes across studies with slightly different criteria for sample inclusion. Of the thirteen overlapping genes found, three were selected for further study based on the information about those genes and other prior evidence demonstrating an association with asthma. I looked for SNPs (single nucleotide polymorphisms) in these genes that were associated with asthma in existing studies. SNPs were investigated using bioinformatics approaches to examine ways they could affect gene expression. Results: The SNPs and genes selected for further analysis included: rs200196635 (p <; 0.0001) located in MYB Proto-Oncogene Like 1 (MYBL1), rs110199 (p<;0.0001) located in Pyrin and Hin Domain Family Member 1 (PYHIN1), and rs1588265 (p <; 0.0001) located in Phosphodiesterase 4D (PDE4D). The SnP rs200196635 is found in an exon and is near a DNase cluster. The SNP rs110199 was at enough distance to be in linkage disequilibrium with an SNP in a binding site for a transcription factor (CTCF). Rs1588265 was not near any landmarks based on the tracks used. Conclusions: The Single-Nucleotide Polymorphism (SNP) rs200196635 was near a DNase cluster which is normally found near regulatory elements. This could lead to cells multiplying and smooth muscle contracting in response to an environmental stimulus. Rs1101999 is not at a distance to influence the CTCF factor but it rather can be in linkage disequilibrium with CTCF and can act as a marker. The CTCF binding factor could lead to PYHIN1 being repressed and there to be increased multiplication of immune cells along with increased antibodies causing the airways to contract in response to an environmental stimulus [13]. This research attempted to identify genes that span asthma phenotypes and categorize them into functional groups. It took a different approach to furthering knowledge of the selected genes by viewing SNPs correlated to asthma and speculating how outside factors may lead to asthma, therefore, crossing the boundaries of clinical definitions.