Phylogenetic analyses of the HLA-DRB1 gene based on the DR haplotypes

基于 DR 单倍型的 HLA-DRB1 基因的系统发育分析

• 批准号: 14340237
• 负责人: HOHJOH Hirohiko
• 金额: $ 7.42万
• 依托单位: National Center of Neurology and Psychiatry (NCNP)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14340237/
• 关键词: HLA; DRB1 gene; Haplotype; Phylogenic tree; DR53 group

The human leukocyte antigen (HLA)-DRB1 is a highly polymorphic gene with a large number of alleles in the human genome, and the DR subregion including DRB1 also possesses polymorphism in terms of its genome organization with active DRB genes and their pseudogenes. Classification of DRB1 alleles based on the DR groups seems to be an important parameter for studying the phylogeny of the DRB1 alleles. Conventional phylogenetic trees for the HLA-DRB1 alleles constructed by the neighbor-joining and UPGMA methods using nucleotide sequences of the DRB1 alleles suggest that DRB1^*0701 may have diverged from other DRB1 alleles before the separation of the human and chimpanzee species because of a large number of nucleotide changes in DRB1^*0701 compared with any of the other DRB1 alleles. In this study we show the new evidence that the haplotypes centering on DRB1^*0701 and DRB1^*04 alleles are the most homologous. This suggests that these haplotypes have derived from the common-ancestral haplo … More type, and that they have likely retained the complete linkage disequilibrium even after the divergence of the DRB1^*0701 and DRB1^*04 allelic lineages. Together with the corresponding haplotype carrying chimpanzee DRB1^*0701 which has a high sequence homology to HLA-DRB1^*0701,these haplotypes reveal that : i)the DRB1^*04 allelic lineage may have been generated from the DRB1^*0701 lineage after the separation of the human and chimpanzee species, ii)the DRB1^*04 allelic lineage has possibly higher substitution rate of DRB1 compared with pseudogene and neutral region, and iii)there could be a significant difference in the substitution rate of DRB1 between the DRB1^*0701 and DRB1^*04 allelic lineages. Based on the difference between the present and previous results, we would like to propose that phylogenetic studies using not only nucleotide sequences of the DRB1 alleles but also haplotypes centering on the alleles should be conducted for understanding detailed phylogenetic relationships of the DRB1 alleles. Less

人类白细胞抗原(人类白细胞抗原)-DRB1是一种高度多态的基因，在人类基因组中存在大量的等位基因，包括DRB1在内的DR亚区在基因组组织结构上也具有多态现象，具有活性的DRB基因及其假基因。基于DR组的DRB1等位基因分类似乎是研究DRB1等位基因系统发育的重要参数。由Neighbor-Join和UPGMA方法构建的基于DRB1等位基因核苷酸序列的传统系统发育树表明，在人类和黑猩猩物种分离之前，DRB1^*0701可能已经偏离了其他DRB1等位基因，因为与任何其他DRB1等位基因相比，DRB1^*0701存在着大量的核苷酸变化。在本研究中，我们发现了以DRB1^*0701和DRB1^*04为核心的单倍型同源性最高的新证据。这表明这些单倍型来源于共同祖先的单倍体…。DRB1^*0701和DRB1^*04等位基因谱系分化后，可能仍保持着完全连锁不平衡。结合与人类白细胞抗原-DRB1^*0701高度同源的黑猩猩DRB1^*0701的单倍型，这些单倍型表明：1)DRB1^*04等位基因谱系可能是人类和黑猩猩物种分离后产生的；2)DRB1^*04等位基因谱系与假基因和中性区相比可能具有更高的DRB1替换率；3)DRB1^*0701和DRB1*04等位基因谱系之间可能存在显著差异。根据目前和以前结果的差异，我们建议不仅要利用DRB1等位基因的核苷酸序列进行系统发育研究，而且要以等位基因为中心进行单倍型研究，以了解DRB1等位基因的详细系统发育关系。较少

项目成果

H.Hohjoh: "Enhancement of RNAi activity by improved siRNA duplexes"FEBS Letters. 557. 193-198 (2004)

H.Hohjoh：“通过改进的 siRNA 双链体增强 RNAi 活性”FEBS Letters。

Omi K, et al.: "CD36 polymorphism is associated with protection from cerebral malaria."Am J Hum Genet. 72. 365-374 (2003)

Omi K 等人：“CD36 多态性与预防脑型疟疾有关。”Am J Hum Genet。

北條 浩彦: "RNAi・その基礎と応用 はじめに"医学のあゆみ. 208. 647-648 (2004)

Hirohiko Hojo：“RNAi：其基础知识和应用介绍”医学史 208. 647-648 (2004)。

H.Hohjoh et al.: "Recent divergence of the HLA-DRB1^*04 allelic lineage from the DRB1^*0701 lineage after the separation of the human and chimpanzee species"Immunogenetics. (in press). (2003)

H.Hohjoh 等人：“人类和黑猩猩物种分离后，HLA-DRB1^*04 等位基因谱系与 DRB1^*0701 谱系的近期分歧”。

小見和也, 北條浩彦: "神経細胞のRNAiと応用"医学のあゆみ. 208. 659-663 (2004)

Kazuya Omi、Hirohiko Hojo：“神经元中的 RNAi 及其应用”医学史 208. 659-663 (2004)。