RT Journal
A1 Wang, Zihua
A1 Andrews, Peter
A1 Kendall, Jude
A1 Ma, Beicong
A1 Hakker, Inessa
A1 Rodgers, Linda
A1 Ronemus, Michael
A1 Wigler, Michael
A1 Levy, Dan
T1 SMASH, a fragmentation and sequencing method for genomic copy number analysis
JF Genome Research 
JO Genome Research 
YR 2016 
FD June 01 
VO 26 
IS 6 
SP 844 
OP 851 
DO 10.1101/gr.201491.115 
UL http://genome.cshlp.org/content/26/6/844.abstract 
AB 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 DNA 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.