the core clock loop at all. Animal studies While the Per3 gene is a paralog to the PER1 and PER2 genes, studies in animals generally show that it does not contribute significantly to circadian rhythms. Functional Per3-/- animals experience only small changes in free-running period, and do not respond significantly differently to light pulses. Per1-/- and Per2-/- animals experience a significant change in free-running period; however, knocking out Per3 in addition to either Per1 or Per2 has little effect on free-running rhythms. Furthermore, Per1-/-Per2-/- mice are completely arrhythmic, indicating that these two genes have much more importance to the biological clock than Per3. Per3 knockout mice experience a slightly shortened period of locomotor activity (by 0.5 hr) and are less sensitive to light, in that they entrain more slowly to changes in the light-dark cycle. PER3 may be involved in the suppression of behavioral activity in response to light, although mPer3 expression is not necessary for circadian rhythms. Clinical significance The PER3 “length” polymorphism in the 54-bp repeat sequence in exon 18 (GenBank accession no. AB047686) is a structural polymorphism due to an insertion or deletion of 18 amino acids in a region encoding a putative phosphorylation domain. The polymorphism has been associated with diurnal preference and delayed sleep phase syndrome. A longer allele polymorphism is associated with “morningness” and the short allele with “eveningness.” The short allele is also associated with delayed sleep phase syndrome. The length polymorphism has also been shown to inhibit adipogenesis and Per3 knockout mice were shown to have increased adipose tissue and decreased muscle tissue compared to wild type. Additionally, the presence of the length polymorphism has also been shown to be associated with type 2 diabetes mellitus (T2DM) patients as compared to non-diabetic control patients. The PER3-P415A/H417R polymorphism has been linked to familial advanced sleep phase syndrome in humans, as well as to seasonal affective disorder, though when knocked in to mice, the polymorphism causes a delayed sleep phase. Gene Orthologs The following is a list of some orthologs of the PER3 gene in other species: PER3 (P. troglodytes) PER3 (M. mulatta) PER3 (C. lupus) PER3 (H. sapiens) PER3 (B. taurus) Per3 (M. musculus) Per3 (R. norvegicus) PER3 (G. gallus) per3 (X. tropicalis) per3 (D. rerio) Paralogs PER1 PER2 Gene location The human PER3 gene is located on chromosome 1 at the following location: Start: 7,784,320 bp Finish: 7,845,181 bp Length: 60,862 bases