Characterization of the genetic basis of human olfactory variance

• Applicants: Professor Dr. Hanns Hatt; Professor Dr. Thomas Hummel
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2009 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 122490878

The ability to detect individual odors and the corresponding odor quality rating is highly variable between individuals. It shows a high plasticity dependent on odor exposure history and olfactory experience. For many chemicals, a high percentage of the human population is specifically anosmic. The reason underlying this individual variance is largely unknown. In the last years, research on human genomics intensively focused on genetic variations between individuals. One of the main reasons for individuality is the occurrence of millions of single nucleotide polymorphisms (SNPs) making each genome unique. In addition, in a controlled training paradigm, some of the initial anosmics can learn to perceive the respective odorous substance when exposed to it several times. For the well documented case of androstenone, initially anosmic people can be separated into olfactory learners and non-learners. This clearly points to a participation of a second mechanism, namely plasticity of the olfactory system and olfactory learning in addition to the genetic reasons. In the proposed project, we plan to characterize olfactory learning on the level of human olfactory perception and underlying physiological principals in a mouse model. In the human experimental learning paradigm, we will expose subjects several times daily to odors towards which they have been shown to be anosmic; measurements will be performed using psychophysical, electrophysiological and imaging techniques. Recently, it was shown that odor exposure leads to changes of protein expression patterns. We intend to characterize such expression pattern changes in the mouse OE induced by odorant exposure regimes similar to that used in human learning experiments. Expression of genes will be analyzed by next generation sequencing (NGS) based transcriptome analysis that allows parallel quantitative analysis of all expressed genes as well as the detection of induced expression changes. The last project part will investigate the correlation of olfactory learning abilities with a possible genetic basis of anosmia for androstenone. It is planned to genotype olfactory learners and non-learners by analyzing SNP variations in ORs and exome genotyping. The proposed project will elucidate the basis of variations in human odor perception in respect to the interplay of olfactory learning, olfactory plasticity on a transcriptome level and genetic variation in mammals.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1392: Integrative Analysis of Olfaction
• Participating Person: Dr. Günter Gisselmann