GENETIC DISSECTION OF VENTILATORY TRAITS

Case Western Reserve University, Cleveland OH

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Abstract

DESCRIPTION: Previous studies offer evidence for a substantial genetic influence on ventilation and the ventilatory response to chemical loading. It is now feasible to begin to identify genes involved in ventilation and to test the hypothesis that genetic variance is due to a few loci with major effects (major genes) or from many loci with small effects (polygenes). Research will apply quantitative genetic analyses to ventilation and ventilatory responses to acute ventilatory challenge with carbon dioxide in adult males and females from two common strains of laboratory rats, selected for both genetic and ventilatory trait diversity, and the F1 and F2 progeny of these strains. Values for ventilation and its components (tidal volume, frequency and inspiratory time) will be collected at rest and when breathing is stimulated with hypercapnia. Oxygen consumption and carbon dioxide production, metabolic rate, and measures of body mass will complete phenotype characterization. Analyses will model for the strength and mode(s) of inheritance and in order to utilize a high density genetic linkage map to find loci correlating with respiratory frequency and the ventilatory response to 7 percent CO2 inhalation, traits for which preliminary data suggest high inheritance. Quantitative trait linkage will also serve to confirm mathematical models of the mode(s) of transmission and the presence of polygenes and major genes. The localization of ventilation and ventilatory response genes by this approach will complement knowledge gained by current molecular studies of candidate physiologic systems and proteins. Results will be relevant to illnesses known to result from, or be exacerbated by, poor or excessive ventilatory responses to environmental and pathophysiologic stresses.