PhD defence G. (Gabriela) Dankova

Summary:

Over the past 15 years, genome-wide association studies (GWASs) have revealed an unprecedented number of human genomic loci associated with a great multitude of phenotypes, including various externally visible characteristics that are highly heritable. GWASs demonstrate that appearance traits as well as other complex traits are in general associated with large numbers of distinct genomic regions (provided large enough sample size used), and thus, presumably affected by many different genes. Each of the associated genomic regions typically contains multiple single nucleotide polymorphisms (SNPs) from which one or more can be biologically functional in the studied trait, hence can explain the genetic association signal. However, for majority of the appearance traits studied by GWAS to date, the actual molecular mechanisms through which the associated SNPs influence the physical characteristics is unknown. As most of the GWAS significant SNPs reside in non-coding genomic DNA, they potentially affect phenotypes through regulation of processes involved in gene expression, such as transcription. Indeed, a few previous studies have shown a transcriptional regulatory role of SNPs associated with appearance traits, which largely focused on human pigmentation traits. The research presented in this thesis aimed to further explore the functional biology underlying genetic associations with appearance traits previously identified by GWAS, including pigmentation traits but extending to others too. Particularly, I studied potential involvement of the appearance-associated SNPs in regulation of gene transcription.