FineStructure DNA Mapping Studies oftheChromosomal Region Harboring theGenetic Defect in Neurofibromatosis TypeI

Summary Tobetter map thelocation ofthe von Recklinghausen neurofibromatosis (NF1) gene,we havecharacterized a somatic cell hybrid designated 7AE-11. Thismicrocell-mediated, chromosome-transfer construct harbors a centromeric segmentanda neo-marked segmentfromthedistal long arm ofhumanchromosome 17.We haveidentified 269cosmid clones withhumansequencesfrom a 7AE-11library and,using a panel ofsomatic cell hybrids with a total ofsixchromosome 17qbreakpoints, havemapped240ofthese clones on chromosome 17q.Thepanel included a hybrid (NF13) carrying a der(22) chromosome that was isolated from an NF1patient with a balanced translocation, t(17;22) (qll.2;qll.2). Fifty-three ofthecosmids map into a region spanning theNF13breakpoint, asdefined bythetwoclosest flanking breakpoints (17q11.2 and17q11.2-q12). RFLPclones from a subset ofthese cosmids havebeenmappedbylinkage analysis in normal reference families, tolocalize theNF1gene more precisely andtoenhance thepotential forgenetic diagnosis ofthis disorder. Thecosmids intheNF1region will bean important resourcefortesting DNA blots oflarge-fragment restriction-enzyme