T Yamamura, J Hikita, M Bleakley, T Hirosawa, A Sato-Otsubo, H Torikai, T Hamajima, Y Nannya, A Demachi-Okamura, E Maruya, H Saji, Y Yamamoto, T Takahashi, N Emi, Y Morishima, Y Kodera, K Kuzushima, S R Riddell, S Ogawa, Y Akatsuka
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引用次数: 5
摘要
次要组织相容性(H)抗原是人白细胞抗原匹配异体造血干细胞移植后移植物抗宿主病和移植物抗肿瘤反应的靶标。最近,我们报道了一种连锁不平衡块的遗传定位策略,该策略使用来自国际HapMap项目的大型数据集,结合传统的免疫学分析,来评估小H抗原特异性T细胞对HapMap b淋巴细胞系的识别。在这项研究中,我们构建并提供了一个在线互动程序,并展示了其用于搜索与次要H抗原产生有关的单核苷酸多态性(snp)的实用性。该网站名为“HapMap SNP Scanner”,可以将t细胞识别和其他数据与来自CEU, JPT, CHB和YRI的基因分型数据集结合起来,提供与观察到的表型相关的候选SNP列表。该方法将极大地促进发现负责次要H抗原的新snp,并适用于分析其他特定细胞表型(例如药物敏感性),以确定可能从基于snp的定制治疗中受益的个体。
HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype.
Minor histocompatibility (H) antigens are targets of graft-vs-host disease and graft-vs-tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B-lymphoid cell line by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single-nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as 'HapMap SNP Scanner', and can incorporate T-cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.