Identification of medium-sized genomic deletions with low coverage, mate-paired restricted tags.
BACKGROUND
Genomic deletions are known to be widespread in many species. Variant sequencing-based approaches for identifying deletions have been developed, but their powers to detect those deletions that affect medium-sized regions are limited when the sequencing coverage is low.


RESULTS
We present a cost-effective method for identifying medium-sized deletions in genomic regions with low genomic coverage. Two mate-paired libraries were separately constructed from human cancerous tissue to generate paired short reads (ditags) from restriction fragments digested with a 4-base restriction enzyme. A total of 3 Gb of paired reads (1.0× genome size) was collected, and 175 deletions were inferred by identifying the ditags with disorder alignments to the reference genome sequence. Sanger sequencing results confirmed an overall detection accuracy of 95%. Good reproducibility was verified by the deletions that were detected by both libraries.


CONCLUSIONS
We provide an approach to accurately identify medium-sized deletions in large genomes with low sequence coverage. It can be applied in studies of comparative genomics and in the identification of germline and somatic variants.
Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, PR China.
Qiang
Q
Gong
Yong
Y
Tao
Jian-Rong
JR
Yang
Jun
J
Cai
Yunfei
Y
Yuan
Jue
J
Ruan
Jin
J
Yang
Hailiang
H
Liu
Wanghua
W
Li
Xuemei
X
Lu
Shi-Mei
SM
Zhuang
San Ming
SM
Wang
Chung-I
CI
Wu
D019295:Computational Biology; D004262:DNA Restriction Enzymes / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
D004262:DNA Restriction Enzymes