SMASH, a fragmentation and sequencing method for genomic copy number analysis
- Zihua Wang,
- Peter Andrews,
- Jude Kendall,
- Beicong Ma,
- Inessa Hakker,
- Linda Rodgers,
- Michael Ronemus,
- Michael Wigler and
- Dan Levy1
- ↵* Corresponding author; email: levy{at}cshl.edu
Abstract
Copy number variants (CNVs) underlie a significant amount of genetic diversity and disease. CNVs can be detected by a number of means, including chromosomal microarray analysis (CMA) and whole genome sequencing (WGS), but these approaches suffer from either limited resolution (CMA) or are highly expensive for routine screening (both CMA and WGS). As an alternative, we have developed a next-generation sequencing-based method for CNV analysis termed SMASH, for Short Multiply Aggregated Sequence Homologies. SMASH utilizes random fragmentation of input genomic DNAs to create chimeric sequence reads, from which multiple mappable tags can be parsed using maximal almost-unique matches (MAMs). The SMASH tags are then binned and segmented generating a profile of genomic copy number at the desired resolution. Because fewer reads are necessary relative to WGS to give accurate CNV data, SMASH libraries can be highly multiplexed, allowing large numbers of individuals to be analyzed at low cost. Increased genomic resolution can be achieved by sequencing to higher depth.
- Received November 3, 2015.
- Accepted April 12, 2016.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.
