Structural variation mutagenesis of the human genome: Impact on disease and evolution.
Structural variation mutagenesis of the human genome: Impact on disease and evolution.
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DOI：
10.1002/em.21943
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发表时间：
2015-06
影响因子：
2.8
通讯作者：
Lupski JR
中科院分区：
文献类型：
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作者：
Lupski JR
沃森-克里克碱基对变化，或单核苷酸变异（SNV），长期以来被认为是突变的来源。然而，DNA结构变异，包括复制和删除拷贝数变异（CNV）以及拷贝数中性反转和易位，在多大程度上导致人类基因组变异和疾病，直到最近才得到认识。此外，没有预见到结构变体（SV）的潜在复杂性；因此，复杂基因组重排（CGR）的频率以及这些事件是如何形成的仍然是一个谜。基因组疾病是由于基因组重排而不是基于序列的变化引起的疾病，基因组结构引起基因组不稳定，这一概念描述了不同于染色体综合征和单基因孟德尔病的新一类疾病。然而，正是对CNV/SV形成机制的理解促进了对人类生物学和疾病的进一步了解，并为人类基因组和基因进化提供了见解。
Watson-Crick base-pair changes, or single-nucleotide variants (SNV), have long been known as a source of mutations. However, the extent to which DNA structural variation, including duplication and deletion copy number variants (CNV) and copy number neutral inversions and translocations, contribute to human genome variation and disease has been appreciated only recently. Moreover, the potential complexity of structural variants (SV) was not envisioned; thus, the frequency of complex genomic rearrangements (CGR) and how such events form remained a mystery. The concept of genomic disorders, diseases due to genomic rearrangements and not sequence-based changes for which genomic architecture incite genomic instability, delineated a new category of conditions distinct from chromosomal syndromes and single-gene Mendelian diseases. Nevertheless, it is the mechanistic understanding of CNV/SV formation that has promoted further understanding of human biology and disease and provided insights into human genome and gene evolution.