利用高通量SNP基因分型检测低水平混合嵌合

A. Nakorchevsky, E. Flores, Li Xiangyang, Tao Hong, A. Nygren
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引用次数: 2

摘要

同种异体骨髓移植(BMT)或干细胞移植(SCT)的接受者需要临床监测,以便早期诊断诸如排斥反应、移植物抗宿主病(GVHD)或恶性肿瘤复发等移植后不良反应。在临床环境中,通过监测最小残留病(MRD)和测量外周血淋巴细胞(PBL)的混合嵌合量来实现移植受者的分类。虽然MRD监测涉及检测恶性肿瘤特异性标记,但测量混合嵌合的程度可以通过一般的基于pcr的方法来实现。我们已经开发了一种SNP基因分型方法来检测PBL和基因组DNA中的低水平混合嵌合。灵敏度是通过测量92个独立SNP标记的队列中基因分型数据的累积偏度来实现的。该方法对10%、5%和2%混合嵌合样品的敏感性为0.98,特异性为0.90。该方法的总特异性为0.98,准确度为0.95。结果与一组临床样本的STR数据吻合100%。与已建立的方法相比,这种方法的优点是它不需要疾病特异性标记,并且可以多路复用。该方法和分析软件也可与其他基因分型和测序技术一起使用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Detection of Low Level Mixed Chimerism Using High Throughput SNP Genotyping
Recipients of allogeneic bone marrow transplants (BMT) or stem cell transplants (SCT) require clinical monitoring to allow for early diagnosis of such post-transplant adverse effects as rejection, graft vs. host disease (GVHD), or a malignancy relapse. Triaging of the transplant recipients in clinical settings is achieved by monitoring the Minimal Residual Disease (MRD) and measuring the amount of mixed chimerism in peripheral blood lymphocytes (PBL). While MRD monitoring involves detection of the malignancy-specific markers, measuring the extent of mixed chimerism can be achieved via general PCR-based methods. We have developed a SNP genotyping method to detect low levels of mixed chimerism in PBL and genomic DNA. Sensitivity is achieved by measuring a cumulative skew in genotyping data across a cohort of 92 independent SNP markers. This method showed a sensitivity of 0.98 and a specificity of 0.90 for 10%, 5%, and 2% mixed chimerism samples. The overall specificity of the method is 0.98 and the accuracy is 0.95. The results show 100% concordance with the STR data for a set of clinical samples. The advantage of this method compared to already established methodologies is that it does not require disease-specific markers and can be multiplexed. The method and the analysis software can also be used with other genotyping and sequencing technologies.
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