Caracterização molecular do gene Per3 em primatas: foco no sagüi (Callithrix jacchus)

• Autor(a) principal: Sabino, Flávia Cal [UNIFESP]
• Data de Publicação: 2009
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://repositorio.unifesp.br/handle/11600/9192
• topic: Per3; 2.VNTR; Preferência diurna; Cronobiologia; Evolução dos primatas

The Periods genes (Per1-3) are important in the generation of circadian rhythms. Mutations in these genes have strong effects on the circadian rhythm and are associated with sleep disorders in humans. Among these genes, Per3 has a special feature, the presence of a variable number in tandem repeat in the coding region. This repeat in tandem is associated with diurnal preference (morning / afternoon), with DSPS and sleep homeostasis. It is known that the length of these repeats in tandem varies among different species; being that the length of each repetition is 54 nucleotides. In the genome of marmosets (Callithrix jacchus), this region has seven repeats, whereas in other primates, this same region has different lengths and can vary from three to five repetitions. The characterization and annotation of Per3 gene in other primates (as in Homo sapiens) is already well known, however, there has been a lack of characterization and annotation of the Period3 in Callithrix jacchus. In this scenario and considering marmoset as a primate of interest for use as a model organism in several studies in the field of biological rhythms, this project presents a complete characterization of Per3 gene in Callithrix jacchus. In this characterization was included: the definition of exons´ and introns´ regions, the search for polymorphism, the analysis of neutrality, the identification and analysis of transposable elements and non-coding RNA, and comparing the length of the variable number in tandem repeat between New World primates. The Per3 in marmoset has 74,739 base pairs and has an alignment score of 77, when aligned with the sequence of the human gene, and 97, when aligned with the sequence of marmoset available on the platform of the University of California Santa Cruz. Three CpG islands and 20 transcription factors binding sites were identified, by in silico analysis, in the promoter region of this gene in the marmoset. Were also identified 115 insertions of transposable elements in Per3 gene, and the long interspersed nuclear elements and short interspersed nuclear elements of the dominant classes. About non-coding RNA, 102 possible candidates were obtained through the prediction via bioinformatics techniques that use the analysis approach of comparison with other primates. In the region of repeat in tandem, were found five single nucleotide polymorphisms and four of these are non-synonymous. When this region of repeat was examined to verify the polymorphism length, only one marmoset (in eighty) showed to be heterozygous (seven and six replicates). No variable number repeat in tandem was found in non-primate mammals. In the new world primates there are variations in the length of this repeat region, ranging from two to eleven repeats. The sequencing and characterization of the gene Per3 in marmoset will allow several other future behavioral studies using this animal as a model organism.