A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-MbBAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region

Chromosomal region 11q22-q23 is a frequent target for deletion during the d evelopment of many solid tumour types, including breast, ovary, cervix, sto mach, bladder carcinomas and melanoma. One of the most commonly deleted sub regions contains the SDHD gene, which encodes the small subunit of cytochro me b (cybS) in mitochondrial complex II (succinate-ubiquinone oxidoreductas e). Germline mutations in SDHD cause hereditary paraganglioma type 1 (PGL1) , and suggest a tumour suppressor role for cybS. We present a high-resoluti on physical map spanning SDHD, covered by 19 YACs and 20 BACs. An approxima te 1.1-Mb gene-rich region around SDHD is spanned by a complete BAC contig. Twenty-six new STSs are developed from the BAC clone ends. In addition to the discovery and characterisation of 15 new simple tandem repeat polymorph isms, we provide integrated positional information for 33 ESTs and known ge nes, including KIAA1391, POU2AF1 (OBF1), PPP2R1B, CRYAB, HSPB2, DLAT, IL-18 , PTPS, KIAA0781 and KAIA4591, which is mapped by NotI site cloning. We des cribe full-length transcript sequence for PPP2R1B, encoding the protein pho sphatase 2A regulatory subunit A beta isoform. We also discover a processed pseudogene for USA-CYP, a cyclophilin associated with U4/U6 snRPNs, and a novel gene, DDP2, encoding a mitochondrial protein similar to the X-linked deafness-dystonia protein, which is juxtaposed 5'-to-5' to SDHD. This map w ill help assess this gene-rich region in PGL and in other common tumours.