title: A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region.
abstract: Chromosomal region 11q22-q23 is a frequent target for deletion during the development of many solid tumour types, including breast, ovary, cervix, stomach, bladder carcinomas and melanoma. One of the most commonly deleted subregions contains the SDHD gene, which encodes the small subunit of cytochrome b (cybS) in mitochondrial complex II (succinate-ubiquinone oxidoreductase). Germline mutations in SDHD cause hereditary paraganglioma type 1 (PGL1), and suggest a tumour suppressor role for cybS. We present a high-resolution physical map spanning SDHD, covered by 19 YACs and 20 BACs. An approximate 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 polymorphisms, we provide integrated positional information for 33 ESTs and known genes, including KIAA1391, POU2AF1 (OBF1), PPP2R1B, CRYAB, HSPB2, DLAT, IL-18, PTPS, KIAA0781 and KAIA4591, which is mapped by NotI site cloning. We describe full-length transcript sequence for PPP2R1B, encoding the protein phosphatase 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 will help assess this gene-rich region in PGL and in other common tumours.
authors: Department of Psychiatry, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. baysalbe@msx.upmc.edu
authors: B E
authors: BE
authors: Baysal
authors: J E
authors: JE
authors: Willett-Brozick
authors: P E
authors: PE
authors: Taschner
authors: J G
authors: JG
authors: Dauwerse
authors: P
authors: P
authors: Devilee
authors: B
authors: B
authors: Devlin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003001:Cloning, Molecular; D003573:Cytochrome b Group / Q000737:chemistry / Q000235:genetics; D042963:Electron Transport Complex II; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2; D015183:Restriction Mapping; D017384:Sequence Deletion; D016324:Sequence Tagged Sites; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D003573:Cytochrome b Group; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2