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
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
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DOI：
10.1038/sj.ejhg.5200585
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发表时间：
2001-02-01
影响因子：
5.2
通讯作者：
Devlin, B
中科院分区：
文献类型：
--
作者：
Baysal, BE;Willett-Brozick, JE;Devlin, B
染色体区域 11q22-q23 是许多实体瘤类型（包括乳腺癌、卵巢癌、子宫颈癌、胃癌、膀胱癌和黑色素瘤）发展过程中常见的缺失靶点。最常见缺失的亚区之一包含 SDHD 基因，该基因编码线粒体复合物 II（琥珀酸泛醌氧化还原酶）中细胞色素 b (cybS) 的小亚基。 SDHD 的种系突变会导致 1 型遗传性副神经节瘤 (PGL1)，并表明 cybS 具有肿瘤抑制作用。我们提出了一个跨越 SDHD 的高分辨率物理图，由 19 个 YAC 和 20 个 BAC 覆盖。 SDHD 周围大约 1.1 Mb 的基因丰富区域由完整的 BAC 重叠群跨越。从 BAC 克隆末端开发出 26 个新的 STS。除了发现和表征 15 个新的简单串联重复多态性之外，我们还提供了 33 个 EST 和已知基因的集成位置信息，包括 KIAA1391、POU2AF1 (OBF1)、PPP2R1B、CRYAB、HSPB2、DLAT、IL-18、PTPS、KIAA0781 和 KAIA4591（通过 NotI 位点克隆进行定位）。我们描述了 PPP2R1B 的全长转录序列，编码蛋白磷酸酶 2A 调节亚基 A beta 亚型。我们还发现了 USA-CYP 的加工假基因，一种与 U4/U6 snRPN 相关的亲环蛋白，以及一种新基因 DDP2，编码类似于 X 连锁耳聋肌张力障碍蛋白的线粒体蛋白，该蛋白与 SDHD 并列在 5' 至 5' 端。该图谱将有助于评估 PGL 和其他常见肿瘤中的这一基因丰富区域。
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.