SMASH, a Fragmentation and Sequencing Method for Genomic Copy Number Analysis

Overview

Journal Genome Res

Specialty Genetics

Date 2016 May 20

PMID 27197213

Citations 17

Authors

Zihua Wang

Peter Andrews

Jude Kendall

BeiCong Ma

Inessa Hakker

Linda Rodgers

Michael Ronemus

Michael Wigler

Dan Levy

Affiliations

Soon will be listed here.

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 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.

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