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Identifying Biomarkers of the MHC Gene to Investigate Chemosensory Discrimination

To better understand the mechanisms underlying the major histocompatibility complex (MHC)‐dependent chemosensory signals, it is critical to chemically identify MHC‐dependent odorants. Urine samples from MHC‐genotyped mice were analyzed using capillary gas chromatography. Employing multivariate analysis and pattern recognition techniques on the chromatographic data, it is possible to classify mice by their MHC genotype and explore which chemical compounds are biomarkers capable of discrimination. Soft Independent Modeling of Class Analogy (SIMCA) of the data was performed and indicated that the observed genotypes were easily distinguishable and well separated, a strong indication that specific compounds differentiated the genotypes. Based on the SIMCA model, a graph of the discriminating power of each compound within the model was generated. The compounds exhibiting high genotype‐discriminating power were dimethyldisulfide, methyl methylsulfenylmethyl disulfide, Z‐5,5‐Dimethyl‐2‐ethylidenetetrahydrofuran, and E‐5,5‐Dimethyl‐2‐ethylidenetetrahydrofuran. The structural similarity between the two disulfide compounds along with the similarity of the two tetrahydrofuran compounds suggest that there may be a biochemical explanation for the role that these four compounds play in differentiating mice with dissimilar MHC genes. Funded by HHMI Undergraduate Science Education Program.