UC San Diego

Zfp423 is a 30-zinc finger transcription factor with potential to integrate several canonical signaling pathways. Nur12 mutant mice lacking Zfp423 showed a range of clinically relevant phenotypes, which are strain dependent. The survival rate for BALB/c (BALB) is ~70%, while the survival of mutant on C57BL/6J (B6) is 0%. This discrepancy of survival rate between BALB and B6 indicated a genetic interaction that we pursued through linkage analysis.

To identify linkage, we combined genotypes from 367 F2 intercross mutant (nur12/nur12) progeny of BALBnur12/nur12 and B6+/+ mice with genotype data from 320 previously collected F2 intercross progeny, from which we determined a need to double the sample size. We found chromosome 5 and 17 passed the significance threshold (LOD=3.4, α < 0.05) after running a genome-wide one degree of freedom Chi-square test on the animals that are homozygous B6. We also collected survival data on 367 more recent progeny so that we could test for loci showing time-dependent contributions, for which we employed a two-part test designed for right-censored data. For the two-part analysis, chromosome 5 passed the significant threshold (LOD=3.4) and seven chromosomes passed the suggestive threshold (LOD =2.0), suggesting that multiple loci that control the quantitative trait-survival.