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Aneuploidy: Using genetic instability to preserve a haploid genome?

by Ramdath, Ramona Sherry

Abstract (Summary)
Aneuploidy occurs in many cancers, and is a sign of genetic instability in the genome. We use two different techniques- single nucleotide polymorphisms (SNPs) and gene expression arrays to investigate two aspects of aneuploidy- the pattern of genetic instability causing aneuploidy, and the reason aneuploidy occurs. SNP technology was employed to obtain areas of loss of heterozygosity (LOH) in a prostate cancer cell line (DU-145), as a means of looking at genetic instability. Using a novel method of analysis we were able to eliminate noise in both normal and cancer samples, and to visualize large quantities of data in a graphical manner. We observed several areas of genetic instability that can be linked to the cancer phenotype. Using gene expression arrays, we investigated the expression of genes in 210 human cell lines and 2,035 human tissues of multiple origins, both cancer and normal, to look at why aneuploidy occurs. We found 778 genes that are commonly expressed in all 2,245 samples, are distributed throughout the human genome, and have mostly metabolic functions, indicating that these are housekeeping genes or universally expressed genes for cell growth and survival. Additionally, we found a subset of variably expressed genes, from where tissue specific genes were also chosen and investigated. We looked at prostate specific tissues, and found that there were some genes that were more highly expressed in the prostate tissues and cell lines, than in other non-prostate samples. We provide evidence that the broken chromosomes in the prostate cell lines are retaining specific regions of their genome, as a means of conserving universally expressed genes, which allows the maintenance of at least a haploid genome, even in cases where an essential gene is mutated or non-functional, in the form of translocations.
Bibliographical Information:

Advisor:

School:University of Toledo Health Science Campus

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:loss of heterozygosity aneuploidy gene expression single nucleotide polymorphisms snps

ISBN:

Date of Publication:07/14/2009

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