THE MOTILIN GENE - SUBREGIONAL LOCALIZATION, TISSUE EXPRESSION, DNA POLYMORPHISMS AND EXCLUSION AS A CANDIDATE GENE FOR THE HLA-ASSOCIATED IMMOTILE CILIA SYNDROME

The product of the human motilin gene (MLN) has an important role in r egulating gastrointestinal motility. The precise chromosomal localisat ion and expression of this gene are still unresolved. Here, we report a detailed study assigning MLN to 6p21.3; MLN is tightly linked to the HLA-DQalpha locus. Moreover, MLN expression has been evaluated in a l arge series of tissues. Positive signals have been obtained for brain, bronchi and a gastrointestinal malignancy. Direct sequencing exon by exon of the codifying region, intron/exon boundaries and promoter has allowed the identification of three DNA polymorphisms, one of which co rresponds to a common protein variant. The chromosomal localisation of MLN, and its expression in broncoepithelial cells suggests that this gene is involved in immotile-cilia syndrome (ICS) disease. Sequence an d segregation analysis of the MLN gene carried out in two families, in which the disease locus was previously assigned to 6p21.3, exclude ML N as a candidate gene for the HLA-associated form of ICS.