Development of SNP catalog toward to disease mapping by sequence determination of the HLA haplotypes

通过 HLA 单倍型的序列确定来开发 SNP 目录以进行疾病图谱

• 批准号: 16310136
• 负责人: SHIINA Takashi
• 金额: $ 10.65万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310136/
• 关键词: HLA; diversity; polymorphism; sequencing; SNP; ハプロタイプ

A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC region (coding units or full contigs) in several human and primate single haplotypes allowed an analysis of Single Nucleotide Variations (SNV) across this entire segment. We demonstrate that the MI-IC-I diversity is not limited to the antigen/TCR binding sites but spreads to surrounding segments. Corroborating data suggests that this hitchhiking diversity, otherwise eliminated by purifying selection in most other genomic sites, has perdured within the MHC perhaps because of the strong biological incentive for constant generation and maintenance of a species-specific diverse allelic repertoire. This was evidenced by the existence of a large reservoir of hvSNV, reminiscent of the fact that most of MHC diversity is de novo generated and not as the result of their trans-species inheritance as initially thought.This result finally puts the MHC in line with the bulk of population and evolutionary genetics data which firmly conclude that a narrow bottleneck has occurred at the origin of our species, -a fact inconsistent with massive flow of alleles from one species to the next as required by the trans-species postulate.Moreover, this fitness in fighting infections seems to have taken its toll on neighboring loci, as the most gene-rich and polymorphic segment around HLA-B is also where most MHC-I diseases are mapped to.Finally, this observation is not limited to the MHC class I region as it extends to the other MHC-disease associations and perhaps to the wider genome.

对于许多 MHC 相关疾病缺乏合理的解释。对几种人类和灵长类单倍型中的 MHC 区域（编码单位或完整重叠群）进行测序，可以对整个片段的单核苷酸变异 (SNV) 进行分析。我们证明 MI-IC-I 多样性不仅限于抗原/TCR 结合位点，还扩散到周围片段。确凿的数据表明，这种搭便车的多样性本来可以通过大多数其他基因组位点的纯化选择而消除，但却在 MHC 中持续存在，这可能是因为物种特异性多样化等位基因库不断产生和维持的强大生物诱因。大量hvSNV的存在证明了这一点，这让人想起大多数MHC多样性是从头产生的，而不是像最初认为的那样是跨物种遗传的结果。这一结果最终使MHC与大量群体和进化遗传学数据相一致，这些数据坚定地得出结论，即我们物种的起源发生了狭窄的瓶颈，这是一个事实不一致的事实 根据跨物种假设的要求，等位基因从一个物种大量流向下一个物种。此外，这种对抗感染的适应性似乎对邻近基因座造成了损害，因为 HLA-B 周围基因最丰富和多态性最丰富的片段也是大多数 MHC-I 疾病所映射的地方。最后，这一观察结果不仅限于 MHC I 类区域，还延伸到其他 MHC 疾病 关联，或许还有更广泛的基因组。

项目成果

Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

• DOI: 10.1371/journal.pbio.0020162
• 发表时间: 2004-06
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Imanishi T;Itoh T;Suzuki Y;O'Donovan C;Fukuchi S;Koyanagi KO;Barrero RA;Tamura T;Yamaguchi-Kabata Y;Tanino M;Yura K;Miyazaki S;Ikeo K;Homma K;Kasprzyk A;Nishikawa T;Hirakawa M;Thierry-Mieg J;Thierry-Mieg D;Ashurst J;Jia L;Nakao M;Thomas MA;Mulder N;Karavidopoulou Y;Jin L;Kim S;Yasuda T;Lenhard B;Eveno E;Suzuki Y;Yamasaki C;Takeda J;Gough C;Hilton P;Fujii Y;Sakai H;Tanaka S;Amid C;Bellgard M;Bonaldo Mde F;Bono H;Bromberg SK;Brookes AJ;Bruford E;Carninci P;Chelala C;Couillault C;de Souza SJ;Debily MA;Devignes MD;Dubchak I;Endo T;Estreicher A;Eyras E;Fukami-Kobayashi K;Gopinath GR;Graudens E;Hahn Y;Han M;Han ZG;Hanada K;Hanaoka H;Harada E;Hashimoto K;Hinz U;Hirai M;Hishiki T;Hopkinson I;Imbeaud S;Inoko H;Kanapin A;Kaneko Y;Kasukawa T;Kelso J;Kersey P;Kikuno R;Kimura K;Korn B;Kuryshev V;Makalowska I;Makino T;Mano S;Mariage-Samson R;Mashima J;Matsuda H;Mewes HW;Minoshima S;Nagai K;Nagasaki H;Nagata N;Nigam R;Ogasawara O;Ohara O;Ohtsubo M;Okada N;Okido T;Oota S;Ota M;Ota T;Otsuki T;Piatier-Tonneau D;Poustka A;Ren SX;Saitou N;Sakai K;Sakamoto S;Sakate R;Schupp I;Servant F;Sherry S;Shiba R;Shimizu N;Shimoyama M;Simpson AJ;Soares B;Steward C;Suwa M;Suzuki M;Takahashi A;Tamiya G;Tanaka H;Taylor T;Terwilliger JD;Unneberg P;Veeramachaneni V;Watanabe S;Wilming L;Yasuda N;Yoo HS;Stodolsky M;Makalowski W;Go M;Nakai K;Takagi T;Kanehisa M;Sakaki Y;Quackenbush J;Okazaki Y;Hayashizaki Y;Hide W;Chakraborty R;Nishikawa K;Sugawara H;Tateno Y;Chen Z;Oishi M;Tonellato P;Apweiler R;Okubo K;Wagner L;Wiemann S;Strausberg RL;Isogai T;Auffray C;Nomura N;Gojobori T;Sugano S
• 通讯作者: Sugano S

hRDH-E2 gene polymorphisms, variable transcriptional start sites, and psoriasis.

hRDH-E2 基因多态性、可变转录起始位点和牛皮癣。

• 发表时间: 2004
• 期刊: Mamm Genome 15
• 作者: Matsuzawa Y;et al.
• 通讯作者: et al.

Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian populations

• DOI: 10.1111/j.1399-0039.2006.00577.x
• 发表时间: 2006-04-01
• 期刊: TISSUE ANTIGENS
• 作者: Sano, K;Shiina, T;Inoko, H
• 通讯作者: Inoko, H

Notes on the maximum likelihood estimation of haplotype frequencies

• DOI: 10.1046/j.1529-8817.2003.00088.x
• 发表时间: 2004-05-01
• 期刊: ANNALS OF HUMAN GENETICS
• 影响因子: 1.9
• 作者: Mano, S;Yasuda, N;Gojobori, T
• 通讯作者: Gojobori, T

Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen

• DOI: 10.1182/blood-2007-02-075911
• 发表时间: 2007-08-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Kawase, Takakazu;Akatsuka, Yoshiki;Takahashi, Toshitada
• 通讯作者: Takahashi, Toshitada