Herrick John, Bensimon Aaron
Genomic Vision, Paris Santé Cochin, Paris.
Methods Mol Biol. 2009;521:71-101. doi: 10.1007/978-1-60327-815-7_5.
The sequencing of the human genome inaugurated a new era in both fundamental and applied genetics. At the same time, the emergence of new technologies for probing the genome has transformed the field of pharmaco-genetics and made personalized genomic profiling and high-throughput screening of new therapeutic agents all but a matter of routine. One of these technologies, molecular combing, has served to bridge the technical gap between the examination of gross chromosomal abnormalities and sequence-specific alterations. Molecular combing provides a new perspective on the structure and dynamics of the human genome at the whole genome and sub-chromosomal levels with a resolution ranging from a few kilobases up to a megabase and more. Originally developed to study genetic rearrangements and to map genes for positional cloning, recent advances have extended the spectrum of its applications to studying the real-time dynamics of the replication of the genome. Understanding how the genome is replicated is essential for elucidating the mechanisms that both maintain genome integrity and result in the instabilities leading to human genetic disease and cancer. In the following, we will examine recent discoveries and advances due to the application of molecular combing to new areas of research in the fields of molecular cytogenetics and cancer genomics.
人类基因组测序开启了基础遗传学和应用遗传学的新纪元。与此同时，探测基因组的新技术的出现改变了药物遗传学领域，并使个性化基因组分析和新型治疗药物的高通量筛选几乎成为常规操作。其中一项技术，分子梳技术，填补了染色体总体异常检查与序列特异性改变检查之间的技术空白。分子梳技术在全基因组和亚染色体水平上，以从几千碱基到兆碱基甚至更高的分辨率，为人类基因组的结构和动态提供了新视角。分子梳技术最初是为研究基因重排和绘制用于定位克隆的基因图谱而开发的，最近的进展将其应用范围扩展到了研究基因组复制的实时动态。了解基因组如何复制对于阐明维持基因组完整性以及导致人类遗传疾病和癌症的不稳定性的机制至关重要。接下来，我们将探讨由于分子梳技术应用于分子细胞遗传学和癌症基因组学领域的新研究领域而取得的最新发现和进展。
