ISH differs from immunohistochemistry which typically localizes proteins in tissue sections. ISH can be performed on a variety of targets, including RNA within cells, DNA in metaphase chromosome preparations obtained from mitotic cells, or DNA in interphase nuclei from cells in the non-mitotic phases. ISH not only has the advantages of detection in morphological context, but also is favored by people for its high sensitivity to nucleic acid detection. ISH has been widely used in clinical cytogenetics, tumor biology, gene mapping and chromosome evolution research.

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