Structural Variation of the Human Genome: What is it, how do you find it, and what does it do?

Author: A. Sharp
Submitted: Saturday 4th of September 2010 01:20:13 PM
Submitted by: egf
Educational levels: expert, qc3



The widespread use of array–comparative genomic hybridization (array-CGH) for the detection of copy number variants (CNVs) in both research and clinical laboratories has created a renaissance in the field of molecular cytogenetics, revealing that the human genome contains both a wealth of structural polymorphism and many novel genomic disorders. Our current knowledge of the extent of human structural variation shows that the human genome is a highly dynamic structure that shows significant large-scale variation from the currently published genome reference sequence. While some of these are associated with phenotypic variation and disease, others are apparently benign. A new generation of experimental platforms enable structural variants to be identified with increasing resolution, and will require the development of more sophisticated methods to assess the pathogenic significance of novel structural variants if these technologies are to be of clinical utility. Indeed, we are now entering an era in which technologies to detect CNVs have advanced much faster than our understanding of the consequences of these variants on human phenotypes, and I argue that over the last few years the problem has now become one of interpretation rather than identification. This problem is made more complex by the realization that many genomic disorders show highly variable penetrance, blurring the boundary of how to define benign vs. pathogenic variants. I will discuss insights from recent research which shed light on potential mechanisms that may underlie this phenomenon, and possible methods to determine the genetic elements that are responsible for the associated phenotype.


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A. Sharp. Structural Variation of the Human Genome: What is it, how do you find it, and what does it do?. EUROGENE portal. September 2010. online:


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