Differential inspiratory timing is genetically linked to mouse chromosome 3

Genetic control ofdifferential inspiratory timing(TI) at baseline has beenpreviously demonstrated among inbred mouse strains. The inheritancepattern for TI between C3H/HeJ(C3; 188 ± 3 ms) and C57BL/6J (B6; 111 ± 2 ms) progenitors wasconsistent with a two-gene model. By using the strain distributionpattern for recombinant inbred strains derived from C3 and B6progenitors, 100% concordance was established betweenTI phenotypes and DNA markers onmouse chromosome 3. This genotype-phenotype hypothesis was tested bytyping 52 B6C3F₂(F₂) progeny by using simplesequence repeat DNA markers (n = 21)polymorphic between C3 and B6 strains on mouse chromosome 3. Linkageanalysis compared marker genotypes to baseline ventilatory phenotypesby computing log-likelihood values. A putative quantitative trait locuslocated in proximity to D3Mit119 wassignificantly associated with baselineTI phenotypes. At the peak(log-likelihood = 3.3), the putative quantitative trait locusdetermined 25% of the phenotypic variance inTI among F₂ progeny. In conclusion, thisgenetic model of ventilatory characteristics demonstrated an importantlinkage between differential baseline TI and a candidate genomicregion on mouse chromosome 3.