**3.8 The** *Hcs7***-interval genes most differentially expressed between C3H and B6 are immune genes**

To identify potential candidate genes and pathways regulated by the *Hcs7* region, we collected livers from DEN-treated B6 and 2R8 mice at 13 days, 28 hours after DEN injection. RNA from these livers was reverse-transcribed and hybridized to Agilent whole-genome arrays, in competition with a B6 mixed-sex control, to identify differentially expressed genes. These arrays carry 43,379 probes representing most genes in the genome. Of the 44 genes in the 175.35 to 178.64 Mb region, 35 are represented by probes. The remaining nine include genes for three spliceosomal RNAs, two olfactory receptors, one protein of unknown function, and three pyrin-domain-containing genes. Genome-wide, *Ifi202b* is the only significantly differentially expressed transcript based on FDR correction (*q* < 10-2). The expression of *Ifi202b* is 57-fold higher in line 2R8 than in B6.

To identify potential candidates that may not be expressed at 13 days, RNA from three B6 and three 2R8 tumors was reverse transcribed and hybridized individually in competition with the mixed-sex control DNA. Genome-wide, *Ifi202b* was again the only significantly differentially expressed transcript, with levels 48-fold higher in 2R8 tumors than in B6 tumors (genome-wide FDR *q* < 0.05). When limiting analysis of the expression array data set to only the 35 candidate genes in the 175.35 to 178.64 Mb minimal region, both *Ifi202b* and the closely related *Aim2* (*Absent in melanoma 2*) were expressed at significantly different levels (*q* < 10-4 and *q* < 10-2, respectively).

Recent resequencing of the C3H genome has revealed many SNPs in the *Hcs7* region. Data compiled by the Mouse Genome Database (MGD) at the Mouse Genome Informatics website (Blake et al., 2011; URL: http://www.informatics.jax.org; 8/2011) show that the C3H alleles of eight genes in the *Hcs7* region encode amino acids that differ from B6. *Ifi202b* carries a Thr/Ser polymorphism. The most dramatic changes lie in *Mndal*, which carries Arg/Gly and Asp/Tyr polymorphisms. Other genes in the interval with non-synonomous SNPs include *Olfr433, Olfr419, Olfr220, Fmn2, Chml,* and *Exo1*.
