Microarray-based ultra-high resolution discovery of genomic deletion mutations

BMC Genomics

Nicholas P Harberd³  Jiannis Ragoussis¹  Richard Mott¹  Aziz Mithani²  Dilair Baban¹  Caifu Jiang³  Xiangchao Gan⁴  Carly Brown³  Eric J Belfield³ 

[1] Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK;Department of Biology, LUMS School of Science and Engineering, Sector U-DHA, Lahore 54792, Pakistan;Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK;Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg, Cologne 50829, Germany

关键词: Probe density;    Comparative genomic hybridization;    Genome;    Microarray;    Deletion;    Mutation;   

Others  :  1217651
DOI  :  10.1186/1471-2164-15-224

 received in 2013-11-01, accepted in 2014-02-28,  发布年份 2014

【 摘 要 】

Background

Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low.

Results

Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size.

Conclusions

Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence.

【 授权许可】

   
2014 Belfield et al.; licensee BioMed Central Ltd.

【 图 表 】

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