Radiation Hybrid Mapping of Chromosomal Region 2p15–p16: Integration of Expressed and Polymorphic Sequences Maps at the Carney Complex (CNC) and Doyne Honeycomb Retinal Dystrophy (DHRD) Loci

Abstract

Chromosomal region 2p15–p16, which corresponds to the genetic interval flanked by polymorphic markers D2S119 and D2S378 and covers a genetic distance of approximately 16 cM, is underrepresented in the existing maps of chromosome 2. This is primarily due to two large gaps of unknown physical distance within the known yeast and bacterial artificial chromosome (YAC and BAC, respectively) maps. In constructing a YAC/BAC contig covering 2p15–p16, a total of 55 sequence-tagged sites (25 of which are polymorphic), including new sequences derived from chromosomal walking, and 38 expressed sequence tags were screened by a commercially available RH panel (Stanford G3). A total of 45 of these sequences were placed; 32 of them were assigned at unique sites. The high-resolution TNG3 RH panel was then used to define further the chromosomal order of markers contained in the region flanked by D2S391 and D2S2153. This region harbors the genes for two autosomal dominant disorders, Carney complex (CNC), a multiple neoplasia syndrome, and Doyne honeycomb retinal dystrophy (DHRD), a disease leading to blindness at a young age. This is the first attempt to order cloned sequences in chromosomal region 2p15–p16, an area apparently resistant to YAC cloning. Construction of the 2p15–p16 RH map is critical for identifying the genes responsible for CNC and DHRD, as well as for the molecular elucidation of a chromosomal region that is frequently rearranged in tumors.