Physiological and Genomic Consequences of Intermittent hypoxia - Selected Contribution: Variation in acute hypoxic ventilatory response is linked to mouse chromosome 9

Genetic determinants confer variation among inbred mouse strains with respe ct to the magnitude and pattern of breathing during acute hypoxic challenge . Specifically, inheritance patterns derived from C3H/HeJ (C3) and C57BL/6J (B6) parental strains suggest that differences in hypoxic ventilatory resp onse (HVR) are controlled by as few as two genes. The present study demonst rates that at least one genetic determinant is located on mouse chromosome 9. This genotype-phenotype association was established by phenotyping 52 B6 C3F(2) (F-2) offspring for HVR characteristics. A genome-wide screen was pe rformed using microsatellite DNA markers (n = 176) polymorphic between C3 a nd B6 mice. By computing log-likelihood values (LOD scores), linkage analys is compared marker genotypes with minute ventilation ((V) over dot E), tida l volume (VT), and mean inspiratory flow (VT/TI, where TI is inspiratory ti me) during acute hypoxic challenge (inspired O-2 fraction = 0.10, inspired CO2 fraction = 0.03 in N-2). A putative quantitative trait locus (QTL) posi tioned in the vicinity of D9Mit207 was significantly associated with hypoxi c (V) over dot E (LOD = 4.5), VT (LOD = 4.0), and VT/TI (LOD = 5.1). For ea ch of the three HVR characteristics, the putative QTL explained more than 3 0% of the phenotypic variation among F-2 offspring. In conclusion, this gen etic model of differential HVR characteristics demonstrates that a locus si milar to 33 centimorgans from the centromere on mouse chromosome 9 confers a substantial proportion of the variance in (V) over dot E, VT, and VT/TI d uring acute hypoxic challenge.