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O papel modulador do gene AIRE - capes

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IntroductionThe thymus is an important organ implicated in the control of the mainfunctions of the immune system, providing a specialized microenvironment forthe maturation of thymocytes into positive TCR α/β T cells [1,2]. Organfunctioning begins early during fetal development, when immature thymocytesfrom the bone marrow reach the thymus and thousand of <strong>gene</strong>s aresimultaneously modulated in both, with thymocytes and thymic stromacontributing to tolerance induction to self-antigens [3-8].Deciphering these <strong>gene</strong>s is a complex task and DNA microarray technology,including mathematical and statistical algorithms for data analysis, such ashierarchical clustering [9] and significance analysis of microarrays (SAM) [10],have permitted the description of the modulation of several of such <strong>gene</strong>s,featuring <strong>gene</strong> expression signatures [6-8,11] .Recent subsuming realized that most biochemical relationships among <strong>gene</strong>sact in a synchronized fashion, involving many <strong>gene</strong>s at once, in which one <strong>gene</strong>can exert many functions and one function can be exerted by many <strong>gene</strong>s [12].Accordingly, a biological phenomenon needs to be interpreted as a wholebiochemical system and in order to grasp it, a comprehensive data set needs tobe produced.One example of a highly complex biochemical system is thymocytedifferentiation into mature T cells. It occurs within the fetal thymus and alldevelopmental stages are distinguishable by their expression of a combinationof clusters of differentiation (CD) cell-surface markers.This is a highly modulated phenomenon, whose central molecular machineryis formed by the recombinase complex (RAG-1 and RAG-2) directly implicated237

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