To identify cis-acting polymorphisms in Per3 that cause expression variation between B and D alleles, we examined Per3 sequence differences using the recently sequenced genome of DBA/2J.39 There are a total of 163 SNPs and 30 indels in Per3 between the B6 and D2 genomes. Of these, four are non-synonymous mutations in exons 1 (Pro10Leu), 9 (Arg372Gln), 13 (Phe500Leu) and 15 (Glu590Gly) (Table 2). We used the SIFT and PolyPhen algorithms to predict the impact of these four non-synonymous mutations on protein function. The mutations Pro10Leu in exon 1 and Phe500Leu in exon 9 are predicted to be damaging and deleterious by SIFT and PolyPhen 2, respectively. The mutations Phe500Leu in exon 13 and Glu590Gly in exon 15 are predicted to be deleterious by PolyPhen 2 only. These amino-acid changes can potentially affect the structure and/or function of Per3 and have an influence on the expression of downstream genes.
