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Departments of Anesthesiology and Environmental Health Sciences, The Johns Hopkins University, Baltimore, Maryland 21205
Genetic control of differential inspiratory timing (TI) at baseline has been previously demonstrated among inbred mouse strains. The inheritance pattern for TI between C3H/HeJ (C3; 188 ± 3 ms) and C57BL/6J (B6; 111 ± 2 ms) progenitors was consistent with a two-gene model. By using the strain distribution pattern for recombinant inbred strains derived from C3 and B6 progenitors, 100% concordance was established between TI phenotypes and DNA markers on mouse chromosome 3. This genotype-phenotype hypothesis was tested by typing 52 B6C3F2 (F2) progeny by using simple sequence repeat DNA markers (n = 21) polymorphic between C3 and B6 strains on mouse chromosome 3. Linkage analysis compared marker genotypes to baseline ventilatory phenotypes by computing log-likelihood values. A putative quantitative trait locus located in proximity to D3Mit119 was significantly associated with baseline TI phenotypes. At the peak (log-likelihood = 3.3), the putative quantitative trait locus determined 25% of the phenotypic variance in TI among F2 progeny. In conclusion, this genetic model of ventilatory characteristics demonstrated an important linkage between differential baseline TI and a candidate genomic region on mouse chromosome 3.
control of breathing; linkage analysis; C3H/HeJ; C57BL/6J; BXH recombinant inbred strains
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