A transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans.

The mammalian olfactory system displays species-specific adaptations to different ecological niches. To investigate the evolutionary dynamics of olfactory sensory neuron (OSN) subtypes across mammalian evolution, we applied RNA sequencing of whole olfactory mucosa samples from mouse, rat, dog, marmoset, macaque, and human. We find that OSN subtypes, representative of all known mouse chemosensory receptor gene families, are present in all analyzed species. Further, we show that OSN subtypes expressing canonical olfactory receptors are distributed across a large dynamic range and that homologous subtypes can be either highly abundant across all species or species/order specific. Highly abundant mouse and human OSN subtypes detect odorants with similar sensory profiles and sense ecologically relevant odorants, such as mouse semiochemicals or human key food odorants. Together, our results allow for a better understanding of the evolution of mammalian olfaction in mammals and provide insights into the possible functions of highly abundant OSN subtypes

Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains.

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL

Data for Mouse Phenome Database_Reed_Bachmanov_June_2015

Contains body composition data for consomic mic

Data from: Body composition QTLs identified in intercross populations are reproducible in consomic mouse strains

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL

Adiposity QTL <i>Adip20</i> decomposes into at least four loci when dissected using congenic strains

<div><p>An average mouse in midlife weighs between 25 and 30 g, with about a gram of tissue in the largest adipose depot (gonadal), and the weight of this depot differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier gonadal depots on average than do 129P3/J mice. To understand the genetic contributions to this trait, we mapped several quantitative trait loci (QTLs) for gonadal depot weight in an F₂ intercross population. Our goal here was to fine-map one of these QTLs, <i>Adip20</i> (formerly <i>Adip5</i>), on mouse chromosome 9. To that end, we analyzed the weight of the gonadal adipose depot from newly created congenic strains. Results from the sequential comparison method indicated at least four rather than one QTL; two of the QTLs were less than 0.5 Mb apart, with opposing directions of allelic effect. Different types of evidence (missense and regulatory genetic variation, human adiposity/body mass index orthologues, and differential gene expression) implicated numerous candidate genes from the four QTL regions. These results highlight the value of mouse congenic strains and the value of this sequential method to dissect challenging genetic architecture.</p></div

QTLs detection in consomic mice: Average values of body size and composition measures in inbred and consomics strains.

<p>Body weight (top), body length (middle), and adiposity (bottom) in inbred and consomic strains (means ± SEM). Left panels: Strains with 129 genetic background. Right panels: Strains with B6 genetic background. Asterisks (*) indicate a nominal difference between consomic strain and its inbred host (p < .0.05), # indicates significant after correction for multiple testing (p<0.0056). ^~p = 0.0545. ^&borderline significance. ^§mice are heavier (top panel) but have similar gonadal weight, thus are leaner after adjustment for body weight.</p

Extraction of differentially expressed genes.

<p>Filtering on a volcano plot of the microarray data analysis of the Experiment 1 (top) and Experiment 2 (bottom). In Experiment 1, we selected the gonadal adipose tissue from male mice from congenic strain 4 with the donor region captured QTL1, QTL2, and QTL3 (42.6 to 58.3 Mb). Half of the mice were heterozygous for the donor region (129/B6; N = 7), and half were littermates homozygous for the donor region (B6/B6; N = 7). Experiment 2 replicated Experiment 1 except with N = 6 mice in each genotype group, for a total of 12 mice. The customized volcano plots depict the estimated log₂-fold change (x-axis) and statistical significance (−log₁₀ p-value; y-axis). Each dot represents one gene. The green dots show genes with absolute log₂-fold change > 0.58 (i.e., 1.5-fold change) and false discovery rate < 0.05; the red dots show genes with false discovery rate < 0.05; the yellow dots show genes with absolute log₂-fold change > 0.58; the black dots show genes that did not reach these statistical thresholds. We label genes that passed any filters by name. Twenty differentially expressed genes are reproducible between Experiment 1 and 2, labeled with blue text and square boxes. Red stars show two genes that passed the filters in one but not both experiments yet are noteworthy because their human orthologues are associated with adiposity or body mass index in genome-wide association studies (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188972#pone.0188972.t002" target="_blank">Table 2</a>). We summarize the additional experimental details in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188972#pone.0188972.s012" target="_blank">S12 Table</a>.</p

Human genome-wide associations within mouse QTLs for adiposity and body mass index.

<p>Human genome-wide associations within mouse QTLs for adiposity and body mass index.</p

QTL confirmation from the consomic strains.

<p>Confirmation criterion–one or more sexes and one or more reciprocal strains differed in the expected direction using a p-value threshold adjusted for multiple testing (see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141494#pone.0141494.t003" target="_blank">Table 3</a></b>). <i>Bdln4</i> and <i>Bdln5</i> are combined because they are both on chromosome 9.</p

Detection of gonadal adipose depot weight QTLs on chromosome 9 by association analyses of a pooled congenic population.

<p>(<b>A</b>) Location of the markers in Mb on mouse chromosome 9 (mChr9); the y-axis is the—log p-values (black line) obtained in a general linear regression model analysis with body weight and strain as covariates (red line, significant threshold; gray line, suggestive). We defined the QTL confidence intervals by two units of—log10 p-value drop from the peak (blue line). For QTL1-QTL4 (Q1-Q4), the shaded peak areas correspond to QTL regions defined by the sequential method. (<b>B and C</b>) Average weight of the gonadal adipose depot by genotype (B6/B6, B6/129; <b>B</b>) and Cohen’s <i>D</i> effect size (<b>C</b>) of <i>rs3723670</i>, the most associated marker (i.e., the marker with the lowest p value). *p<0.0001, difference between genotypes.</p