Differential inspiratory timing is genetically linked to mouse chromosome 3

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.