Elucidation of the evolution of the MHC by genome analysis

通过基因组分析阐明 MHC 的进化

• 批准号: 09044337
• 负责人: INOKO Hidetoshi
• 金额: $ 3.9万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044337/
• 关键词: HLA; paralogous region; 9q33-q34; 1q22-q23; evolution; gene duplication; homologous gene; CD1; ga33-a34; la22-a23; HLA領域; 第9染色体9q33-44領域; 第1染色体1q21-25領域; ゲノム構造

In order to clarify the gene organization of four paralogous regions ; chromosome 6p21.3 (HLA region), the 1q21-q25, 9q33-q34, and 19p13.1-p13.3 regions, and understanding of the evolution of the HLA region, we have analyzed the genomic structure of the HLA class I region, 9q33-q34 and 1q22-q23 region around the CD1 genes by YAC, PAC and BAC clones. The genomic sequence of the 1.8 megabase (Mb) HLA class I entire region, was determined by the shot gun method. In total, 124 genes or candidate gene sequences and 758 microsatellite repeats were found in this region. In addition, the five pair segments which showed high sequence homology to each other were found in the HLA class I region, suggesting that segmental genome duplication must have occurred during the evolution of the human MHC, ln the 9q33-q34 region, three genes which have homologous genes in the HLA region were mapped, HXB -C5 -GRP78 from PCR analyses of the YAC clones, In the 1q22-q23 region, an approximately 1.8 Mb YAC and PAC contig containing thefive CD1 genes were constructed by PCR using locus-specific and STS primer pairs and sequencing of the end regions of PAC clones. Ten genes were located in the telomeric side of CDlE with the order of SPTA 1 - MNDA -FYI - IFI-16 -FCERIA -KRTC7 -CRP -CRPP1 -ARCS - KIAAO 120 . Further, from PCR analyses of the YAC clones which were located on the telomeric side of KIAA 0120, twelve genes were mapped, (ATP1A2 - PXF - CBP -AIM2)- LYAM - (CD48 - LY9 - PPOX) -USF1 - (EAT2 -PBX1) - ALDH9 - RXRG - POU2F1 -CD3Z - ATAC - (FV- ELAM1 - LNHR) -FMO1 - FASL between D1S1705 and WI-6210. Thus, it was revealed that the 1q22-q23 region around the CD1 genes contained a cluster of genes which had immunological importance, such as SPTA 1, FY, IFI-16, ECERIA, ARCS, LYAM, CD48, LY9, SCM, CD3Z, ATAC, ELAM1, LNHR and FASL .

为了弄清染色体6p21.3(HLA区)、1q21-q25、9q33-q34和19p13.1-p13.3区四个平行区域的基因组织，以及了解HLA区的进化，我们用YAC、PAC和BAC克隆分析了CD1基因周围的HLAI类区域、9q33-q34和1q22-q23区域的基因组结构。用鸟枪法测定了1.8兆碱基(Mb)的人类白细胞抗原I类基因全长序列。在该区域共发现124个基因或候选基因序列和758个微卫星重复序列。在人类MHC的进化过程中，发现了5对序列高度同源的片段，提示在人类MHC的进化过程中可能发生了节段性基因组复制。在9q33-q34区，定位了3个在HLA区有同源基因的基因，通过对YAC克隆的PCR分析，在1q22-q23区，通过对PAC克隆末端区域的测序，构建了一个约1.8Mb的YAC和PAC重叠群，其中包含5个CD1基因。有10个基因位于CDLE的端粒一侧，其顺序为SPTA 1-MNDA-FYI-IFI-16-FCERIA-KRTC7-CRP-CRPP1-ARCS-KIAAO 120。进一步对位于KIAA 0120端粒一侧的YAC克隆进行了PCR分析，定位到12个基因：(ATP1A2-PXF-CBP-AIM2)-Lyam-(CD48-LY9-ppox)-USF1-(EAT2-Pbx1)-ALDH9-RXRG-POU2F1-CD3Z-ATAC-(Fv-ELAM1-LNHR)-FMO1-FASL。因此，CD1基因周围的1q22-q23区域包含一组具有免疫学意义的基因，如SPTA 1、FY、IFI-16、ECERIA、ARCS、LYAM、CD48、LY9、SCM、CD3Z、ATAC、ELAM1、LNHR和FASL。

项目成果

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Mizuki N 等人：“MICA 基因跨膜区的三联体重复多态性：六个 GCT 重复与白塞病的密切关联。”

猪子英俊 他(共著): "医学大辞典 第18版" 南山堂, 193-196,222,488,518-519,882,884 (1998)

Hidetoshi Inoko 等人（合著者）：《医学词典第 18 版》Nanzando，193-196,222,488,518-519,882,884 (1998)

安藤麻子 他: "蛋白質核酸酵素別冊 ゲノムサイエンス" 共立出版, 2704-2713 (1997)

安藤麻子 (Asako Ando) 等：“蛋白质核酸酶分离卷基因组科学”Kyoritsu Shuppan，2704-2713 (1997)

Mizuki N,et al.: "Nucleotide sequence analysis of the HLA class I region spanning the 237 kb segment around the HLA-B and C genes." Genomics. 42. 55-66 (1997)

Mizuki N 等人：“跨越 HLA-B 和 C 基因周围 237 kb 片段的 HLA I 类区域的核苷酸序列分析。”

Shiina T,et al.: "Nucleotide sequencing analysis of the 146 kb segment around the lkBL and MICA genes at the centromenric end of the HLA class I region" Genomics. 47. 372-382 (1998)

Shiina T 等人：“HLA I 类区域着丝粒端 lkBL 和 MICA 基因周围 146 kb 片段的核苷酸测序分析”基因组学。