GENETIC-MAPPING STUDIES OF 40 LOCI AND 23 COSMIDS IN CHROMOSOME-11P13-11Q13, AND EXCLUSION OF MU-CALPAIN AS THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 GENE

Forty loci (16 polymorphic and 24 non-polymorphic) together with 23 co smids isolated from a chromosome 11-specific library were used to cons truct a detailed genetic map of 11p13-11q13. The map was constructed b y using a panel of 13 somatic cell hybrids that sub-divided this regio n into 19 intervals, a meiotic mapping panel of 33 multiple endocrine neoplasia type 1 (MEN1) families (134 affected and 269 unaffected memb ers) and a mitotic mapping panel that was used to identify loss of het erozygosity in 38 MEN1-associated tumours. The results defined the mos t likely order of the 16 loci as being: 11pter-D11S871-(D11S288, 913-D 11S970-D11S97-D11S146-INT2-D11S971-D11S533-11 qter. The meiotic mappin g studies indicated that the most likely location of the MEN1 gene was in the interval flanked by PYGM and D11S97, and the results of mitoti c mapping suggested a possible location of the MEN1 gene telomeric to SEA. Mapping studies of the gene encoding mu-calpain (CAPN1) located C APN1 to 11q13 and in the vicinity of the MEN1 locus. However, mutation al analysis studies did not detect any germ-line CAPN1 DNA sequence ab normalities in 47 unrelated MEN1 patients and the results therefore ex clude CAPN1 as the MEN1 gene. The detailed genetic map that has been c onstructed of the 11p13-11q13 region should facilitate the constructio n of a physical map and the identification of candidate genes for dise ase loci mapped to this region.