Linkage analysis of 7 polymorphic markers at chromosome 11p11.2-11q13 in 27 multiple endocrine neoplasia type 1 families.

Abstract

The multiple endocrine neoplasia type 1 (MEN1) locus has been previously localized to 11q13 by combined tumour deletion mapping and linkage studies. Family linkage analysis has defined the locus order as 11 cen-PGA-(PYGM, MEN1)-(D11S97, D11S146)-INT2-11qter, and tumour deletion mapping studies have suggested that the MEN1 locus is proximal to D11S146 but distal to PYGM. In order to establish further the location of MEN1, we have utilized the seven polymorphic DNA probes: D11S288, D11S149, PGA, PYGM, D11S97, D11S146 and INT2, in linkage studies of 339 members (116 affected) from 27 MEN1 families. Linkage between MEN1 and 6 of the 7 loci was established, and the highest peak lod scores [Z(theta)] were observed with PYGM and D11S97 at Z(theta) = 13.71, theta = 0.047 and Z(theta) = 13.76, theta = 0.076 respectively. Multilocus analysis suggested the most likely locus order as: 11 pter-(D11S288, D11S149)-11 cen-PGA-PYGM-MEN1-D11S97-D11S146-INT2-1 1qter. In addition, an examination of individual recombinants indicated a centromeric location of D11S149 in relation to D11S288. Thus, the results of our study, which favoured a location of MEN1 proximal to D11S97 and distal to PYGM, have established a panel of recombinants that will facilitate further meiotic mapping studies of the MEN1 locus.