HUMAN MUCIN GENES ASSIGNED TO 11P15.5 - IDENTIFICATION AND ORGANIZATION OF A CLUSTER OF GENES

Four distinct genes that encode mucins have previously been mapped to chromosome 11p15.5. Three of these genes (MUC2, MUC5AC, and MUC6) show a high level of genetically determined polymorphism and were analyzed in the CEPH families. Linkage analysis placed all three genes on the genetic map in a cluster between HRAS and INS, and more detailed analy sis of recombinant breakpoints revealed that MUC6 is telomeric to MUC2 . Using these recombinants D11S150 was mapped close to MUC2. Ten of th e 11 recombinant chromosomes studied in detail were paternal, and the recombinant events were distributed throughout the 11p15 region, sugge sting high level of recombination observed in 11p15.5 is not due to a particular recombinational hot spot. Pulsed-held gel electrophoresis w as used to make a detailed physical map of the MUC cluster and to inte grate the physical and genetical maps. The gene order was determined t o be HRAS-MUC6-MUC2-MUC5AC-MUC5B-IGF2. The MUC genes span a region of some 400 kb and the map extends 770 kb and contains 15 putative CpG is lands. The order of the MUC genes on the map corresponds to the relati ve order of their expression along the anterior-posterior axis of the body, suggesting a possible functional significance to the gene order. (C) 1996 Academic Press, Inc.