Genomics Inform.  2014 Dec;12(4):136-144. 10.5808/GI.2014.12.4.136.

Genome Architecture and Its Roles in Human Copy Number Variation

• Chen L
• Zhou W
• Zhang L
• Zhang F

• KMID: 2391488
• DOI: http://doi.org/10.5808/GI.2014.12.4.136

Abstract

Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

Keyword

DNA copy number variations; DNA replication; genetic recombination; genomic instability

MeSH Terms

Base Sequence
DNA
DNA Copy Number Variations
DNA Replication
DNA Replication Timing
Genome*
Genome, Human
Genomic Instability
Humans
Mutagenesis
Recombination, Genetic
DNA