Characterization of Genetic Variation in the Forkhead Box Class O3 Gene (FOXO3) in Sheep

Abstract

FOXO3 is a member of the Forkhead box class O (FOXO) transcription factor family that modulates the transcription of target genes in a variety of cellular functions in lower animals to mammals. It has been implicated in the attenuation of insulin-signaling pathways, including having a potential role in lifespan control in rodents and invertebrates. Recent studies also provide some evidence for an association between ageing, human longevity, and variation in the FOXO3 gene. To date there has been no study on variation in ovine FOXO3 or its relationship to longevity in sheep. In this study, we investigated the variation in exon 2 of ovine FOXO3. This exon encompasses the DNA-binding domain, which is the key regulator of transcription activity in the target genes. To enable investigation of the entire exon 2 of the gene, four overlapping fragments were amplified and analyzed by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing. Seven haplotypes with 10 nucleotide substitutions were identified across the 1422-bp exon 2 fragment. One of these substitutions was predicted to produce an amino acid change (p.M201V). The variation identified in ovine FOXO3 may have an impact on both the structure and function of ovine FOXO3 and, consequently, affect the longevity of sheep.