Bevital AS, c/o Section for Pharmacology, University of Bergen, Bergen, Norway.
Adv Clin Chem. 2011;53:1-29. doi: 10.1016/b978-0-12-385855-9.00001-1.
After completion of the human genome project, the focus of geneticists has shifted to elucidation of gene function and genetic diversity to understand the mechanisms of complex diseases or variation of patient response in drug treatment. In the past decade, many different genotyping techniques have been described for the detection of single-nucleotide polymorphisms (SNPs) and other common polymorphic variants. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is among the most powerful and widely used genotyping technologies. The method offers great flexibility in assay design and enables highly accurate genotyping at high sample throughput. Different strategies for allele discrimination and quantification have been combined with MALDI (hybridization, ligation, cleavage, and primer extension). Approaches based on primer extension have become the most popular applications. This combination enables rapid and reliable multiplexing of SNPs and other common variants, and makes MALDI-TOF-MS well suited for large-scale studies in fine-mapping and verification of genome-wide scans. In contrast to standard genotyping, more demanding approaches have enabled genotyping of DNA pools, molecular haplotyping or the detection of free circulating DNA for prenatal or cancer diagnostics. In addition, MALDI can also be used in novel applications as DNA methylation analysis, expression profiling, and resequencing. This review gives an introduction to multiplex genotyping by MALDI-MS and will focus on the latest developments of this technology.
人类基因组计划完成后，遗传学家的研究重点已经转移到阐明基因功能和遗传多样性，以了解复杂疾病的机制或药物治疗中患者反应的变化。在过去的十年中，已经描述了许多不同的基因分型技术来检测单核苷酸多态性（SNP）和其他常见的多态性变异。基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）是最强大和广泛使用的基因分型技术之一。该方法在检测设计中具有很大的灵活性，并能够以高通量实现高度准确的基因分型。不同的等位基因区分和定量策略已与 MALDI 相结合（杂交、连接、切割和引物延伸）。基于引物延伸的方法已成为最受欢迎的应用。这种组合能够快速可靠地对 SNP 和其他常见变异进行多重检测，使 MALDI-TOF-MS 非常适合用于精细映射和全基因组扫描验证的大规模研究。与标准基因分型相比，更具挑战性的方法使 DNA 池、分子单倍型或游离循环 DNA 的检测（用于产前或癌症诊断）成为可能。此外，MALDI 还可用于 DNA 甲基化分析、表达谱分析和重测序等新应用。本综述介绍了 MALDI-MS 的多重基因分型，并将重点介绍该技术的最新进展。
