Identifying HLA-A regulatory factors

Identifying HLA-A regulatory factors

Associated Students: 
Email Address: 
saiyuri108@gmail.com
Phone Number: 
+27 71 291 1357
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Singh is currently working on determining the factors that affect HLA-A expression in order to improve HIV disease outcome. Human leukocyte antigen (HLA) genes are located within the short arm of chromosome 6 in humans. The HLA Class I genes have traditionally been shown to play a role on the influence of human immune response via the presentation of peptides to adaptive immune cells. Recent studies indicate the expression levels of the HLA molecules also contribute to the function of these genes. Studies have shown expression levels are responsible for progression of certain diseases such as HIV. A study published in the journal Science has shown increased expression of the HLA-A gene results in poor control of HIV and subsequently leads to worse disease outcomes, measured in about 9,700 individuals from 22 cohorts across three ethnic backgrounds (Africans, Caucasians and Hispanics). Determining the factors responsible for regulating HLA-A expression levels will be important for future therapeutic interventions. A previous study has identified DNA methylation as one of the factors responsible for regulating the expression levels at the allelic level. However, DNA methylation is just one of the factors responsible for the regulation of allelic expression levels. Other factors that have greater effects have yet to be identified. This study therefore aims to identify the factors that influence HLA-A expression levels. We plan to firstly determine if variants located within the promoter regions are associated with allelic expression variation. To achieve this goal, we plan to sequence approximately 2 kilobases upstream of the transcription start site to determine which polymorphisms associate with expression variation. After identifying specific mutations associating with allelic expression variation we plan to determine the mechanism responsible. Using predictive transcription factor binding tools we will determine potential regulatory factors responsible. These putative transcription factors will be confirmed using techniques such as Chromatin Immuno-Precipitation (ChIP) sequencing.