PHYSICAL MAPPING STUDIES AT D15S10 - IMPLICATIONS FOR CANDIDATE GENE IDENTIFICATION IN THE ANGELMAN SYNDROME PRADER-WILLI SYNDROME CHROMOSOME REGION OF 15Q11-Q13/

The Angelman syndrome (AS) and Prader-Willi syndrome (PWS) loci have b een mapped to chromosome 15q11-q13. Chromosomal deletions of differing parental origin in the two syndromes have been interpreted as being d ue to genetic imprinting. Molecular analysis of patients with varying deletions has localized the AS locus to the interval between D15S113 a nd GABRB3 and the PWS locus between D15S13 and D15S113. In the present study, DNA cloning and physical mapping techniques have been used to characterize the AS/PWS chromosome region in the vicinity of D15S10, a locus that is telomeric to D15S113 and centromeric to GABRB3. A CpG i sland near TD3-21 at D15S10 has been cloned, allowing the identificati on of a widely expressed 4.5-kb transcript and providing a novel DNA m arker, OP3, at this locus. OP3 and TD3-21 have been used to construct a long-range physical map extending over approximately 2800 kb. Cluste rs of rare-cutting restriction sites on this map locate four other CpG islands. Since these CpG islands lie within the minimum deletion inte rvals for AS and PWS, they mark the possible locations of candidate ge nes for the two syndromes. (C) 1991 Academic Press, Inc.