An investigation into the evolution of racially biased diseases - Glioma, Using a Drosophila model

Abstract

Glioma is a major form of brain cancer throughout the world and studies have shown that the cases and survival rates of brain cancer differ depending on a person’s race. The only major genetic difference between races is a small amount of DNA bases; single nucleotide polymorphisms (SNP). This is due to little within-species genomic diversity. A predisposition to glioma is neurofibromatosis type 2 (NF2) shown as tumour growth along the spine and brain stem. NF2 encodes one protein, merlin. Merlin has many roles within the cell at both the membrane and nucleus. At the membrane merlin traffics molecules into and out of the cell and regulates many downstream pathways that are associated with cancer development. In the membrane: merlin stabilises the genome, has an impact in cell-cycle regulation and has an influence. Therefore a change in merlin’s function alters the cell, producing many hallmarks of cancer. Glioma and NF2 are both familial, inherited diseases that can pass down and be passed down from parent to offspring. Much research on merlin studies the mutations and potential epigenetic causes of merlin deregulation. Despite this, no study has focused on the inheritance of merlin in relation to its inheritance pattern i.e. Mendelian inheritance. By studying merlin, one can better understand cancer development. Thus by studying the inheritance pattern on merlin, one can deduce the inheritance of familial cancer and the racial bias of brain cancer, confirming merlin’s genetic or epigenetic origin. NF2 is an autosomal-dominant condition, however the inheritance pattern of brain tumour may not correlate to this. So by studying the inheritance pattern of merlin in a human model and studying the DNA methylation of the gene NF2; this could answer the current argument of whether mutant merlin or merlin’s expression patterns cause the phenotype of NF2 and glioma, evidence is available for both. Recent publications have shown that merlin may be a useful biomarker in glioma therapeutics. The aim of this research is to study the inheritance pattern of merlin in human races using a Drosophila model. Firstly, the aim is to examine the inheritance pattern of merlin in Drosophila. Secondly, to examine the inheritance pattern to deduce whether the inheritance/gene mutation is responsible for NF2 or whether epigenetics is the main cause. Studying the inheritance pattern would aid a conclusion of whether mutations of merlin or epigenetic changes to merlin lead to the phenotype of NF2 and glioma.