Investigating human polymorphism density and transcriptional regulation of the galanin gene

• Main Author: Davidson, Scott
• Published: University of Aberdeen 2009
• Subjects: 591.35; Evolutionary genetics : Gene science : Variation (Genetics) : Genomics
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521172

The present study aimed to gain better insights into the distribution of genomic variation, in the form of single nucleotide polymorphisms, within the human genome.  Using set theory, the average SNP density of the human genome was found to be 2.6 SNPs per kilobase.  This figure decreased with increasing evolutionary depth, i.e. conservation.  The conserved exonic, intronic subsets had a lower SNP density than the conserved intergenic subset, suggesting that the conserved exonic and intronic regions are under similar strengths of selective pressure while conserved intergenic regions are under a comparatively weaker selective pressure.  To better understand allelic differences on protein-DNA interactions, an algorithm was designed that scored the difference in binding site prediction for the alleles of an SNP.  The program created, RegSNP, was demonstrated to be more accurate than existing resources, and gives results that are relevant of SNP within binding sites in the literature. A further aim of the present study was to isolate potential regulatory regions of the GAL gene, that has been linked to diseases such as obesity and depression, and identify polymorphisms that may alter transcription factor binding.  One excellent candidate element was found by comparative genomics, Gal5.1, and confirmed by transgenic analysis as a transcriptional enhancer element.  Gal5.1, contained a single SNP that RegSNP predicted to interrupt a thyroid hormone receptor binding site.  However, using transgenic animal and cell biology techniques it was concluded that thyroid hormone receptor does not directly interact with the Gal5.1 element, suggesting that the Gal5.1 element must work in synergy with the GAL promoter to stimulate transcription.