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17 RI lines and 762 chromosomal markers, we have restricted the quinine taste QTL to a \u003c 5 Mb region on distal chromosome 6 that contains 24 Tas2r genes. At least 60 other genes also lie within this interval, including two genes that encode proline-rich salivary proteins, Prp2 and Prh1; these proteins appear to play no direct role in bitter taste [48]. Tas2rs are the most likely candidates for the QHCl quantitative trait gene(s) due to: (1) their expression in taste receptor cells and (2) genetic and functional evidence linking them to the detection of a number of bitter taste stimuli. As of yet there is no evidence for quinine activation of T2Rs from functional assays of these receptors in heterologous cells or membrane preparations, likely due to the lipophilic nature of quinine [23]. However, several physiological studies have suggested that quinine can directly activate G proteins or cationic conductances, or can block K+ channels in taste receptor cells [34-36]. While our data indicates that quinine taste is largely T2R-dependent, it is not exclusively so. For example, the BXD RI lines exhibited a range of quinine sensitivity, with several strains having similar sensitivities to that of B6, some strains with sensitivities similar to that of D2, and a third group with a more intermediate phenotype (Figures 1, 7). This observation is consistent with a polygenic basis for quinine taste [16,26]. Also, a suggestive QTL on chromosome 8 does not contain any Tas2r genes, but does contain a number of genes encoding ion channels, enzymes and members of other receptor families (our unpublished data). It will be interesting to determine whether this suggestive QTL is linked to quinine taste and, if so, whether it is specific for this single bitter stimulus or more broadly related to all bitter taste."}

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17 RI lines and 762 chromosomal markers, we have restricted the quinine taste QTL to a \u003c 5 Mb region on distal chromosome 6 that contains 24 Tas2r genes. At least 60 other genes also lie within this interval, including two genes that encode proline-rich salivary proteins, Prp2 and Prh1; these proteins appear to play no direct role in bitter taste [48]. Tas2rs are the most likely candidates for the QHCl quantitative trait gene(s) due to: (1) their expression in taste receptor cells and (2) genetic and functional evidence linking them to the detection of a number of bitter taste stimuli. As of yet there is no evidence for quinine activation of T2Rs from functional assays of these receptors in heterologous cells or membrane preparations, likely due to the lipophilic nature of quinine [23]. However, several physiological studies have suggested that quinine can directly activate G proteins or cationic conductances, or can block K+ channels in taste receptor cells [34-36]. While our data indicates that quinine taste is largely T2R-dependent, it is not exclusively so. For example, the BXD RI lines exhibited a range of quinine sensitivity, with several strains having similar sensitivities to that of B6, some strains with sensitivities similar to that of D2, and a third group with a more intermediate phenotype (Figures 1, 7). This observation is consistent with a polygenic basis for quinine taste [16,26]. Also, a suggestive QTL on chromosome 8 does not contain any Tas2r genes, but does contain a number of genes encoding ion channels, enzymes and members of other receptor families (our unpublished data). It will be interesting to determine whether this suggestive QTL is linked to quinine taste and, if so, whether it is specific for this single bitter stimulus or more broadly related to all bitter taste."}

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