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Analysis of the gene organization of the whole HLA region

整个HLA区域的基因组织分析

基本信息

批准号：
06044201
负责人：
INOKO Hidetoshi
金额：
$ 6.53万
依托单位：
Tokai University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06044201/
关键词：
HLA region gene organization genomic sequencing cDNA cloning disease susceptible gene polycystic kidney disease salivary gland tumor Behcet's disease psoriasis vulgaris 強直性脊椎炎塩基配列解析疾患原因遺伝子発現遺伝子 HLA コスミドクローン多型性コスミドコンティグ

项目摘要

Characterization of the human MHC region at the nucleotide level will provide an important information on the physical and gene organization of the human chromosome as a model system as well as the development of human diseases. In collaboration with ICRF,Sanger Institute, Western Australia University and Fred Hutchinson Cancer Research Center, we have cloned about 3,000kb area of the human MHC region and searched for new expressed genes by mouse gene probes, detection of CpG islands, cDNA isolation or genomic sequencing analysis.On the centromeric side of the HLA class II region which corresponds to the mouse t complex region, 7 new genes were identified, HSET-HKE1.5-HKE2-HKE3-RING1-HKE6-HKE4-RXRb- from the centromeric side. HKE6 is a possible candidate gene for the development of polycystic kidney disease. An uncharacterized 450kb region harboring the junction between the class II and class III region was colned and so far, four genes, TN-X RAGE,HOX12 and Notch4 (a human homologue of the mouse int-3 gene belonging to a Notch family) were identified. Notch4 is a candidate gene responsible for the development of salivary gland tumor.In order to elucidate the gene organization of the HLA class I region and to identify new genes involved in the development of HLA-class I associated diseases such as Behcet's disease and psoriasis vulgaris, cosmid clones covering the 452 kb region around the HLA-B and -C genes were determined for their nucleotide sequences. Homology and Grail search as well as RT-PCR,Northern hybridization and cDNA cloning analyzes revealed the existence of 21 genes (10 known genes and 11 new genes) and 7 EST-homologous segments. Further, 35 dinucleotide repeats, which will provide a powerful tool for precise mapping of the disease susceptible genes as polymorphic markers, we identified.

在核苷酸水平上对人类MHC区域的表征将提供关于人类染色体作为模型系统的物理和基因组织以及人类疾病发展的重要信息。我们与ICRF、桑格研究所、西澳大利亚大学和弗雷德哈钦森癌症研究中心合作，克隆了人类MHC区域约3,000 kb的区域，并通过小鼠基因探针、CpG岛检测、cDNA分离或基因组测序分析寻找新的表达基因。在对应于小鼠t复合体区域的HLA II类区域的着丝粒侧，鉴定了7个新基因，HSET-HKE 1.5-HKE 2-HKE 3-RING 1-HKE 6-HKE 4-RXRb-来自着丝粒侧。HKE 6可能是多囊肾病发生的候选基因。克隆了一个未鉴定的450 kb的区域，该区域位于II类和III类区域之间的连接处，到目前为止，鉴定了四个基因，TN-X β，HOX 12和Notch 4（属于Notch家族的小鼠int-3基因的人类同源物）。Notch 4是一个与涎腺肿瘤发生有关的候选基因，为了阐明HLA-Ⅰ类区域的基因结构，并鉴定与白塞病和寻常型银屑病等HLA-Ⅰ类相关疾病发生有关的新基因，我们克隆了覆盖HLA-B和HLA-C基因周围452 kb区域的粘粒克隆，测定了它们的核苷酸序列。同源性和Grail搜索以及RT-PCR、北方杂交和cDNA克隆分析表明，共发现21个基因（10个已知基因，11个新基因）和7个EST同源片段。此外，35个二核苷酸重复，这将提供一个强大的工具，精确定位的疾病易感基因作为多态性标记，我们确定。