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Mucin genes encode the polypeptide backbone of the mucin glycoproteins which are expressed on all epithelial surfaces and are major constituents of the mucus layer. Mucins are, thus, expressed at the interface between the external and the internal environment of the organism, and represent the first line of defence of our body. These genes often have an extensive region of repetitive exonic sequence which codes for the heavily glycosylated domain, whose roles include bacterial interactions and gel hydration. This region shows, in several of the genes, considerable inter-individual variation in repeat number and sequence. Because of their site of expression and their high variability in this important domain, mucin genes are good candidates for conferring differences in genetic susceptibility to multifactorial epithelial and inflammatory disease. However, progress in characterizing the genes has been considerably slower than the rest of the genome because of their size and the GC-rich content of the large, repetitive variable region. Some of the issues relating to the study of these genes are discussed in this chapter. In addition, methods and approaches that have been used successfully are described.