The present invention relates to an expression control composition for controlling the expression of a duplicate gene or a method using the same. More particularly, the present invention relates to an expression control composition including a guide nucleic acid capable of targeting the transcriptional regulatory region of a duplicate gene, and a method of controlling a duplicate gene by artificially manipulating and/or modifying the transcriptional regulatory region of a duplicate gene. In addition, the present invention relates to a method of treating or improving a disease caused by gene duplication using the expression control composition for controlling the expression of a duplicate gene.